Vaccines doi: 10.3390/vaccines14080703

Authors: Nicoline Weinreich Reinstrup Renée Hangaard Gidsel Terho Heikkinen Anne Margarita Dyrhol-Riise Lars-Åke Levin Lars Jørgen Østergaard Lars Holger Ehlers

Background: Despite the increasing availability of tailored vaccines, vaccine-preventable respiratory diseases (VPRDs), including influenza, respiratory syncytial virus (RSV), COVID-19, and pneumococcal disease (PD), continue to impose a significant health and economic burden. This study assessed the epidemiological and economic burden of VPRD among adults aged ≥65 across four Nordic countries (Denmark, Sweden, Norway, and Finland). Methods: Data on incidence, hospital admissions, and mortality were obtained from national statistics (week 21, 2024–week 20, 2025) and supplemented with peer-reviewed literature. A static model was developed to quantify epidemiological and economic burden associated with VPRD during the 2024/2025 winter season. Results: During the 2024/2025 season, VPRD resulted in approximately 830,000 symptomatic cases, 60,300 hospital admissions, and 7750 deaths across the Nordic countries. COVID-19 showed the highest estimated incidence and numbers of hospital admissions, followed by influenza, PD, and RSV. Mortality was comparable between COVID-19 and influenza, followed by PD and RSV. Annual healthcare costs were approximately €1132 million, with productivity losses constituting an additional 7%. Conclusions: Despite national vaccination efforts, VPRDs remain a major health and economic burden in the Nordic countries. Strengthening immunization programs through improved vaccine uptake, broader coverage, and use of advanced vaccines may contribute to further reducing this burden.

Vaccines doi: 10.3390/vaccines14080702

Authors: Gyeong-Seo Park Minsung Park Somin Lee Chonghan Kim Byoung Joo Seo

Bovine neonatal diarrhea (BND) is a leading cause of morbidity and mortality in pre-weaned calves. Commercial maternal vaccines targeting bovine rotavirus (BRV), bovine coronavirus (BCoV), and enterotoxigenic Escherichia coli (ETEC) have been available for decades, yet field outbreaks continue in vaccinated herds. This review examined peer-reviewed literature published between January 2019 and March 2026, identified through a structured PubMed search supplemented by reference-list screening. For BRV, a field strain sharing its VP7 genotype with a vaccine component was not neutralized by vaccine-induced antiserum, indicating that genotype concordance does not predict serologic coverage. For BCoV, hemagglutinin-esterase variation and regional lineage divergence indicate surface-protein evolution, although data linking these changes to reduced efficacy are not available. For ETEC, adhesin diversity and antimicrobial resistance affect both vaccination strategy and case management. Maternal vaccination retains biological value, but field performance is constrained by colostral variability, incomplete passive transfer, and product-to-product immunogenic differences. For all three pathogens, antigenic divergence from vaccine strains is located at individual epitopes, receptor-binding domains, or adhesins rather than at the level of whole-pathogen identity. Subunit and multi-epitope antigen designs, for which proof-of-concept constructs have been reported, operate at this level, and their selection requires characterization of candidate antigens for efficacy, diversity, polymorphism, and cross-protective breadth. Such antigen improvements address the pathogen-side gap but not the passive-transfer and mucosal constraints. Functional surveillance to guide antigen updating, field trials that measure passive-transfer efficiency, and adjunctive strategies are identified as priorities for BND control.

Vaccines doi: 10.3390/vaccines14080701

Authors: Samuel W. Rovito Po-Ling Chen Guohua Yang Haley N. Writt Ashley N. Zalla Marissa A. Donofrio Jonathan N. Fogo Richard J. Webby James D. Brien Charles J. Russell

Background: Conformational stability has been shown to modulate the immunogenicity of structural class 1 viral fusion glycoproteins, yet the relationship between influenza A hemagglutinin (HA) stability and antigenicity remains poorly understood. Methods: Here, we screened a panel of 21 A/Hawaii/70/2019 (H1N1) HA mutants for expression, cleavage, and acid and conformational stability in cells. Twelve mutant HA proteins expressed from transfected plasmid constructs that showed relatively robust expression compared to WT also exhibited either altered stability or glycosylation deletion. mRNA-LNPs were generated containing these 12 HAs, along with the wild-type (WT) HA, to investigate the mutational effects on mRNA-LNP vaccine immunogenicity and protection in mice. Hemagglutination inhibition, microneutralization, and total serum IgG ELISAs were performed using a panel of H1N1 antigens to evaluate humoral immune responses at 28 days post vaccination. The vaccinated mice were then subjected to lethal challenge with a forward-drifted H1N1 virus. Results: Most mutant HA candidates elicited WT-like serological responses and provided protection against challenge, although noticeable decreases in serological responses and, to a lesser extent, protection were observed, especially among G72K- and R109E-vaccinated mice. Of note, substitutions at position E107 enhanced total IgG responses against the HA stalk. Modest, but detectable, increases in antibody-dependent cellular cytotoxicity (ADCC) were also observed, particularly with E107R. Although substitution-specific differences in weight loss were found in E107-vaccinated mice challenged with a mouse-adapted Cal/09 virus, these differences were minor, and protection against the forward-drifted challenge virus and a heterologous PR8 challenge virus was no different from that in mice vaccinated with WT HA. Conclusions: These findings demonstrate the ability of specific substitutions to alter components of humoral immunity by shifting HA domain-specific antibody responses, which could prove useful in the design and development of HA vaccine antigens possessing optimized immunogenicity.

Vaccines doi: 10.3390/vaccines14080700

Authors: Tomasz Hikawczuk Dorota Stefanicka-Wojtas Agnieszka Rusiecka Maria Kasprzyk-Smardz Monika Zadka Norbert Zachara Jarosław Zachara Stanisław Karol Manulik Katarzyna Lomper Izabella Uchmanowicz Donata Kurpas

Background: C scales are important measures that can support the vaccination process by analysing the possible reasons for vaccination hesitancy. In some studies, it is not possible to utilise typical models based on the traditional 3C–7C scales, but it is possible to adjust them by using modified proxy measures and converting individual determinants into variables of similar significance in the logistic regression analysis of a vaccination behavioural model. Objective: The aim of this study was to compare the relationship between determinants defining a vaccination behaviour model based on the classic 3C, 5C, and 7C scales with modified proxy measures and two variables (low vaccine-related fear instead of complacency and exposure to misinformation-prone digital sources instead of conspiracy) and the dependent variable, namely, the vaccination status of patients of primary care centres in Poland from 2024 to 2025. Methods: A cross-sectional study was conducted using a survey and questionnaire data linked with patient records from three Polish health centres (N = 1206, 46.9% rural residents and 53.1% city residents). Demographic data and determinants of three vaccination behaviour models were compared between vaccinated and non-vaccinated patients using Pearson’s χ2 test, while behavioural models based on the 3C, 5C, and 7C scales describing the relationship between independent variables and vaccination status (dependent variable) were prepared using logistic regression. Two of seven determinants were changed. Results: All determinants used in the three logistic regression behavioural models differed significantly between vaccinated and non-vaccinated patients (p < 0.001). Furthermore, independent variables in each behavioural model were significantly related to the dependent variable (p < 0.001). With an increasing number of model determinants, Nagelkerke’s R2 increased from 0.303 to 0.435 and the ROC-AUC from 0.828 to 0.882. However, the VIF value indicated very low multicollinearity of determinants. The Wald test did not reveal a significant relationship between confidence in public health and the dependent variable (p > 0.05, OR 1.17–0.92 for Models 1 and 3, respectively). Conclusions: In the vaccination behavioural models prepared based on empirical data, all determinants were found to be significantly related to the dependent variable. As the number of independent variables in the behavioural model increased, parameters such as the ROC-AUC and Nagelkerke’s R2 also increased, while the Akaike information criterion, which determines the balance between fitting the model to data and its complexity, decreased. No significant individual relationship was found for the determinant “confidence in public health”, but this result confirms observations from other previous studies describing the impact of pandemic fatigue, misinformation, and conflicting expert information on institutional trust.

Vaccines doi: 10.3390/vaccines14080699

Authors: Dong-Wan Kim Seo-Yong Lee So Eon Kim Tae-Jun Kim Hyejin Kim Ji-Hyeon Hwang Sun Young Park Young-Joon Ko Yoon-Hee Lee Jong-Hyeon Park Sung-Han Park

Background: Foot-and-mouth disease (FMD) is a highly contagious viral disease causing substantial economic losses in livestock. Conventional intramuscular (IM) vaccination is widely used for FMD control but may be associated with transient reductions in milk production. This study evaluated whether intradermal (ID) vaccination could induce comparable immune responses and protection while minimizing potential impacts on productivity. Methods: In cattle, the immunogenicity of an experimental bivalent ID vaccine was compared with that of a commercially available IM vaccine by measuring antibody responses for up to 140 days post-vaccination (dpv). Milk production was monitored for 7 dpv in a separate cohort of lactating cattle. Protective efficacy was evaluated in goats following ID vaccination and challenge with a 2025 Republic of Korea serotype O field isolate (O/ME-SA/Ind-2001). Results: ID vaccination induced humoral immune responses comparable to those elicited by IM vaccination throughout the 140-day observation period. Although no statistically significant difference in milk production was observed, the ID group showed a smaller numerical reduction in milk yield. Following viral challenge, ID-vaccinated goats developed rapid neutralizing antibody responses, exhibited no clinical signs, and showed lower viral RNA levels than unvaccinated controls. Conclusions: Intradermal vaccination induced long-lasting immune responses comparable to conventional IM vaccination, was associated with a smaller numerical reduction in milk yield, and protected goats against challenge with a contemporary FMDV field isolate. These findings provide preliminary evidence supporting the potential of ID vaccination as an alternative strategy for FMD control in ruminants and warrant further comparative studies with conventional IM vaccination.

Vaccines doi: 10.3390/vaccines14080698

Authors: Deepak Nagra Kathryn Biddle Katie Bechman Victoria Allen James Galloway

Lyme borreliosis is the most common vector-borne disease in the temperate Northern Hemisphere, with approximately 476,000 diagnoses annually in the United States and over 130,000 reported cases across Europe each year, figures that substantially underestimate true incidence. In 1998, LYMErix became the first licensed vaccine against Lyme borreliosis. Its withdrawal four years later was not driven by evidence of vaccine failure but by the collapse of public confidence, and regulatory endorsement that any successful vaccine programme requires. The field was without a licensed product for twenty-four years. VLA15 (now designated PF-07307405), a second-generation recombinant outer surface protein A vaccine, is now at regulatory submission following phase 3 results reported in March 2026. We examine the barriers that led to LYMErix’s withdrawal, revisit the evidence that generated and sustained the safety controversy and consider whether the conditions now exist for a different outcome. The lessons for a robust post-marketing surveillance programme extend beyond Lyme borreliosis to broader questions about how modern medicine evaluates vaccine risk, interprets safety signals, and communicates under uncertainty.

Vaccines doi: 10.3390/vaccines14080697

Authors: Anete Ogrina-Komarova Zane Kalnina Rebeka Racina Vilija Zeltina Ramona Petrovska Ina Balke Patricija Zaremba Krista Resne Juris Jansons Andris Zeltins

Background: Plant-derived virus-like particles (VLPs) are emerging nanoplatforms for local cancer immunotherapy, yet their relative performance across structurally distinct particles remains insufficiently defined. Methods: We performed a comparative benchmarking study of eleven plant-derived VLPs spanning diverse architectures and functional properties using an integrated workflow of physicochemical characterization, immune-functional profiling, and in vivo evaluation. All VLPs were produced in endotoxin-minimized ClearColi BL21 (DE3), enabling assessment of intrinsic particle-associated immunostimulatory activity with reduced bacterial endotoxin confounding. Results: In vitro, several VLPs stimulated macrophage-associated responses and enhanced tumor cell killing, although classical M1/M2 polarization markers in RAW264.7 cells did not consistently predict functional cytotoxicity. In a subset of candidates, HEK-TLR3 reporter activity varied substantially under RNA-normalized conditions and was not predicted solely by total RNA content or apparent RNA size distribution. Five candidates were advanced to intratumoral evaluation in the male-derived B16-F10 melanoma model, where CCMV-ss and CMVtt showed trends toward reduced tumor progression and increased immune cell infiltration in male mice. Furthermore, host sex-associated differences in baseline immune features were observed, though these must be interpreted with caution given the H-Y antigen-driven immunogenicity inherent to the male-derived B16-F10 model in female hosts. Conclusions: This study establishes a standardized comparative framework linking plant VLP properties with immune-functional performance and identifies CCMV-ss and CMVtt as promising candidates for further development as locally administered cancer immunotherapy nanoplatforms.

Vaccines doi: 10.3390/vaccines14080696

Authors: Susanna Esposito Valentina Fainardi Maria Elena Capra Melodie O. Aricò Angela Lanzoni Francesco Accomando Gaia Giorgia Arnesano Cosimo Neglia Enrico Valletta Giacomo Biasucci Serafina Perrone

Background: Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection and hospitalization in infants. Nirsevimab, a long-acting monoclonal antibody, provides single-dose protection during the RSV season, but the effectiveness of prophylaxis programs depends on sustained parental acceptance and high uptake. This study evaluated changes in parental knowledge, perceptions, and willingness to accept nirsevimab across two consecutive RSV seasons in Emilia-Romagna, Italy. Methods: Two multicenter cross-sectional surveys were conducted during consecutive RSV seasons, 2024–2025 and 2025–2026, using a comparable questionnaire and recruitment approach. Parents or legal guardians of infants eligible for nirsevimab completed a semi-structured questionnaire during routine counseling in neonatal units. Survey 1 included 1042 respondents and survey 2 included 867 respondents. Sociodemographic characteristics, RSV awareness, knowledge and perception of nirsevimab, willingness to accept prophylaxis, trust in healthcare providers and the healthcare system, preferred information sources, and willingness to pay were compared between seasons. Results: Willingness to administer nirsevimab remained high and stable—87.04% in survey 1 and 88.00% in survey 2. Awareness of RSV-related risks increased from 68.23% to 73.47% (p < 0.05), and correct identification of nirsevimab as an antibody increased from 65.93% to 71.74% (p < 0.01). Explicit refusal rose slightly from 2.21% to 3.81% (p < 0.05). In survey 2, acceptance was associated with higher education, awareness of RSV risks, perceived child susceptibility, confidence in efficacy, lower concern about side effects, trust in pediatricians and the healthcare system, and willingness to pay. Notably, acceptance in 2025–2026 was higher among infants born in September–December than among those born in January–March, indicating a late-season decline. Conclusions: Parental acceptance of nirsevimab remained high across two seasons. Future campaigns should address residual knowledge gaps, reinforce communication on safety and efficacy, and sustain high coverage throughout the entire RSV season, particularly among infants born in its final months.

Vaccines doi: 10.3390/vaccines14080695

Authors: Gyeong-Seo Park Somin Lee Minsung Park Minseok Kim Eunhui Lee Sungmin Lee Myung Hyee Kim Byeong Yeal Jung Chonghan Kim Byoung Joo Seo

Background/Objectives: Caseous lymphadenitis (CLA), caused by Corynebacterium pseudotuberculosis, is difficult to control on goat farms because of subclinical infection, abscess rupture, environmental contamination, and repeated herd-level exposure. This study evaluated a Korean inactivated CLA vaccine under commercial goat farm conditions and combined vaccination outcomes with farm-level bacteriological profiling. Methods: Goats from three commercial farms were allocated according to baseline CLA serostatus and vaccination status into seropositive vaccinated, seronegative vaccinated, seropositive non-vaccinated, and seronegative non-vaccinated control groups. Vaccinated goats received two intramuscular doses at weeks 0 and 4. Clinical signs, external abscess occurrence, growth performance, CLA-specific antibody responses, and abscess bacterial loads were monitored. Farm-level microbial profiles were assessed using culture, MALDI-TOF MS, and targeted PCR. Results: Baseline antibody classification showed strong agreement between the commercial CLA ELISA and the in-house whole-bacterial IgG ELISA, with a Spearman’s rho of 0.89 (p < 0.001) and 96.7% classification agreement. Vaccination induced CLA-specific antibody responses in both assays and was not associated with a persistent reduction in growth performance. External abscesses were observed only in baseline seropositive goats. Abscesses occurred in 1/30 vaccinated and 2/15 non-vaccinated seropositive goats, but the difference was not statistically significant (p = 0.254). Microbial profiling showed farm-dependent detection patterns. Conclusions: The vaccine induced CLA-specific antibody responses (immunogenicity) with acceptable tolerability. The exploratory abscess endpoint was underpowered, and clinical protection was not confirmed; larger studies are needed.

Vaccines doi: 10.3390/vaccines14080694

Authors: Hudson R. McAllister Bradly I. Ramirez Sarah F. Capik Kelsey M. Harvey Paul S. Morley Robert J. Valeris-Chacin Brandi B. Karisch Amelia R. Woolums Alexis C. Thompson Matthew A. Scott

Background/Objectives: Bovine respiratory disease (BRD) remains a major concern in cattle research, and the long-term effects of vaccination on health and immune responses are not well defined. This study compared gene expression in vaccinated (VAX) and unvaccinated (NOVAX) preweaned calves and subsequent BRD development during backgrounding. Methods: Whole blood was collected at four timepoints (TIME; T1-4; median age 107, 114, 183, and 230, respectively) from 73 bull calves enrolled in a blinded randomized controlled trial; VAX calves received a commercial attenuated multivalent viral vaccine at T1 and T3. Results: Whole-blood transcriptomics was used to quantify mRNA, identifying 5364 differentially expressed genes (DEGs) for TIME, 84 DEGs for vaccination (VAX), and 129 for BRD status using both glmmSeq and QLF testing (glmmSeq only DEGs: 11,068 TIME, 358 VAX, and 9241 BRD). VAX calves at T3 were clustered uniquely with the enrichment of pathways related to the cellular response to stress, neutrophil degranulation, and antigen processing and presentation compared to NOVAX cattle and VAX at other timepoints. Interferon pathways, natural killer cell responses, and neutrophil activity were generally absent across all timepoints, while antigen presentation pathways were persistently enriched. Regardless of vaccination or future BRD diagnosis, immunological development over time was indicated by DEGs related to adaptive immunity, lymphocyte development, and inflammatory resolution. At T4, cattle diagnosed with BRD during backgrounding had differential gene expression related to oxygen transport, hemoglobin function, and metabolic processes compared to cattle that remained healthy. Conclusions: This study provides insights into the possible genomic mechanisms underlying vaccine responses and preclinical BRD susceptibility in preweaned beef cattle.

Vaccines doi: 10.3390/vaccines14080693

Authors: Mario Caldarelli Pierluigi Rio Carlotta Renna Andrea Marrone Giulia Guazzarotti Antonio Gasbarrini Giovanni Gambassi Rossella Cianci

Non-communicable diseases (NCDs), including cancer, cardiovascular, neurodegenerative, autoimmune, and allergic diseases, account for a significant amount of global morbidity and mortality. Chronic viral infections have not been recognized as NCDs, despite the availability of several therapeutic vaccination strategies against oncogenic viruses, such as the hepatitis B virus (HBV) and the human papillomavirus (HPV). Indeed, chronic viral infection leads to the development and progression of malignancies directly linked to the viruses. These considerations support a connection between NCDs, infectious diseases, and therapeutic vaccination. Recent advances in technology have paved the way to the use of vaccines beyond the prevention of infectious diseases, heralding innovative therapeutic and preventative strategies for a variety of chronic NCDs. Here we will review the state of the art of personalized vaccine strategies for NCDs, with an emphasis on the diverse technological platforms used to develop them, including mRNA and DNA vaccines, viral vectors, dendritic cell-based vaccines, nanoparticle delivery systems, and next-generation adjuvants. The review intends to make the case for personalized and antigen-specific vaccination strategies as a compelling option for precision immunotherapy primarily in oncology, where neoantigen-based vaccines are being developed. In addition, we will also review tolerogenic vaccination strategies, vaccination strategies targeting pathological proteins and pathways in neurodegenerative and cardiovascular diseases, and vaccine-based treatment of chronic viral infections. Current evidence about vaccines suggests that several ways are available to induce an immune response or create tolerance to a disease, and possibly altering its course instead of simply controlling the symptoms. However, many challenges are still to be overcome, including disease variability, how to identify appropriate target antigens, the complexity of manufacturing process, long-term safety, and integration with already established treatments. By virtue of the convergence of multiple fields—immunology, genomics, bioinformatics, and new delivery systems—precision vaccinology is gaining momentum. Thus, it is envisaged that personalized vaccines will be an increasingly essential component of future preventive and therapeutic approaches for non-communicable diseases.

Vaccines doi: 10.3390/vaccines14080692

Authors: Benjamin J. Manchester Jennifer L. Gommerman Shayan Sharif Leonardo Susta Sarah K. Wootton

Existing vectored immunoprophylaxis (VIP) approaches have primarily focused on IgG, which provides systemic protection but is less specialized in mucosal immunity. In contrast, secretory IgA (sIgA) plays a central role at epithelial surfaces, promoting pathogen neutralization while limiting inflammation. Although monoclonal IgA therapies are effective, their short half-life requires repeated dosing. Thus, VIP strategies enabling sustained sIgA expression at mucosal sites could transform mucosal infection prevention and treatment. This review outlines the key challenges associated with in vivo IgA expression and discusses critical considerations for VIP-mediated IgA delivery at mucosal surfaces, with emphasis on its potential for clinical translation. We provide a detailed overview of platforms for targeted IgA expression, including adeno-associated virus (AAV), adenoviral and lentiviral vectors, and lipid nanoparticle-based systems, alongside relevant routes of administration. Additionally, we examine emerging strategies to enhance the robustness, durability, and localization of IgA expression in vivo. Overall, VIP-enabled IgA expression represents an emerging strategy for enhancing mucosal immunity, with continued advances required to establish its role in the prevention and treatment of mucosal infections.

Vaccines doi: 10.3390/vaccines14080691

Authors: Barbara Dema Marta Ulaszewska Alice Lilley Abi Lofts Roo Bhasin Ruth Harvey Piyada Supasa Matěj Hlaváč Susan J. Morris Richard E. Booth Alexander M. P. Byrne Nicola Lewis Alex McSloy Sarah C. Gilbert

Background/objectives: The emergence of highly pathogenic avian influenza A (H5N1) virus infections in dairy cattle in the United States revealed a novel mammalian host and a potential transmission pathway involving raw milk and dairy production systems. Sustained circulation of H5N1 in dairy herds is of concern because ongoing viral adaptation in mammals may increase the risk of efficient mammalian transmission and subsequent zoonotic spread. In response to this emerging threat, we developed a chimpanzee adenovirus (ChAd)-vectored vaccine expressing the haemagglutinin 5 antigen (H5HA) from the dairy cattle isolate A/dairy cattle/Texas. Methods: Lactating dairy cows were vaccinated by either intramuscular (N = 3) or intranasal administration (N = 3). H5HA clade 2.3.4.4b antibodies in cow’s milk and sera were evaluated by ELISA. Hemagglutination and neutralisation capacity were also evaluated. Results: IgG and IgA H5HA-specific antibodies were detected in serum and milk from parenterally vaccinated animals, demonstrating the induction of a systemic immune response. The neutralising antibody responses elicited were only detected in serum of cows vaccinated via the intramuscular route. Conclusions: These preliminary findings support the feasibility of ChAd-vectored vaccination as a strategy to induce humoral immunity in cattle against emerging H5N1 influenza A viruses. Cross-reactive antibody responses against both A/dairy cattle/Texas/24-008749_001/2024 and A/Ibis/Egypt/RLQP-229S/2022 support the capacity of the vaccine to recognise antigenically related H5N1 clade 2.3.4.4b viruses circulating in mammalian and avian reservoirs. Further studies of vaccine efficacy and the immunological mechanism of protection should now be undertaken with the aim of reducing viral transmission and milk-associated shedding in dairy herds.

Vaccines doi: 10.3390/vaccines14080690

Authors: Milena Opacic Olga Labovitiadi Paul de Goede Martinus A.H. Capelle

Background: ExPEC9V was a 9-valent vaccine candidate intended for the prevention of invasive extraintestinal pathogenic Escherichia coli (ExPEC) disease (IED). Here, we describe more than a decade-long formulation development trajectory of this vaccine candidate aimed at establishing a stable, robust and scalable drug product that maintains long-term stability while addressing potential manufacturing challenges and increasing the probability of successful global deployment. Methods: Selected formulation development studies of the ExPEC multivalent vaccine candidate are summarized, spanning formulation screening, confirmation, and design of experiments (DoE)-based robustness, stability and compatibility studies. A formulation initially developed for an early low-valency vaccine candidate was subsequently tested and confirmed for candidates with additional serotypes incorporated based on antigen heterogeneity evidence. Contact materials employed included primary packaging—polycarbonate (PC) and polyethylene terephthalate glycol (PETG) bottles, borosilicate glass vials, stoppers, and prefilled syringes; vessel types—bags and stainless steel vessels used in drug substance (DS) and drug product (DP) manufacturing; and varying concentrations of tungsten and hydrogen peroxide. An evolving analytical panel was applied to assess attributes such as purity, protein concentration and degree of O-acetylation. Results: A phosphate-based formulation containing sorbitol, methionine, and polysorbate 80 showed superior stability in screening and was confirmed as fit for purpose across increasing vaccine valency. The ExPEC 9V drug product displayed remarkable thermal and formulation robustness, long-term (3 years) stability at 2–8 °C in glass vials and prefilled syringes, and compatibility with assessed primary containers and manufacturing materials. DoE-based robustness studies defined acceptable excipient and pH ranges, supporting a wide formulation design space. Conclusions: The development trajectory of the ExPEC9V vaccine candidate demonstrates that early prioritization of a robust, scalable formulation that remains fit for purpose across valency evolution supports a stable late-stage manufacturable drug product.

Vaccines doi: 10.3390/vaccines14080689

Authors: Cameron Andrew Jernigan Hope Reeves Bradley McNeese Cate Moriasi Greg Krempl Joan Walker Ashlea Braun Radhika Gogoi Thanh C. Bui

Background: Human papillomavirus (HPV) is associated with multiple head and neck cancers, many of which are preventable with the 9-valent HPV vaccine. We developed an interactive HPV vaccination education program (IHVEP) to equip patients with HPV-associated cancers to serve as health educators. Objective: To pilot test the adapted IHVEP, evaluate its content using the Information-Motivation-Behavioral Skills (IMB) model and the Suitability Assessment of Materials (SAM) instrument, and identify factors relevant to optimizing digital health interventions. Methods: A previously developed cervical cancer–focused IHVEP was adapted for patients with oropharyngeal cancer. Participants completed the program and participated in semi-structured interviews. Feedback was analyzed and organized into themes aligned with the IMB and SAM frameworks. Results: Participants generally perceived the adapted IHVEP as informative, motivating, and empowering. Key motivators included physician recommendation and a desire to protect others. The program appeared to enhance participants’ perceived ability and self-efficacy to promote HPV vaccination. Modules were described as clear, well-organized, linguistically accessible, and culturally appropriate. Feedback identified areas for improvement related to technology, content, and functionality. Conclusions: Findings suggest that effective digital health interventions may benefit from incorporating training in evaluating health information, ensuring intuitive design and navigation, and including content featuring real individuals. These results will inform further refinement of IHVEP and the development of future digital health interventions.

Vaccines doi: 10.3390/vaccines14080688

Authors: Huijing Xue Troy J. Kemp Hayley North Ligia A. Pinto

Background: Individuals with autoimmune disease, inflammatory bowel disease (IBD), and transplants face a higher risk of severe COVID-19 and breakthrough hospitalizations. It is essential to understand the magnitude and durability of vaccine-induced humoral immune response in these populations. Methods: We evaluated SARS-CoV-2 spike IgG antibody levels and avidity in autoimmune, IBD, transplant, and healthy cohorts following multiple COVID-19 mRNA vaccine doses. Serum samples were collected approximately 1 month (8–52 days) and 6 months (158–202 days) post-vaccination. Antibody levels and avidity were measured using validated ELISA and chaotropic-based avidity assays. Results: Individuals with IBD and individuals with autoimmune disease, especially systemic autoimmune disease, exhibited lower antibody levels and avidity compared with healthy individuals at certain doses and time points. Transplant recipients demonstrated substantial impairments in both antibody levels and avidity, with avidity reduced across all doses and time points. Significantly lower avidity levels were observed in transplant recipients, suggesting challenges in developing or maintaining antibody quality. For example, geometric mean anti-spike IgG levels were substantially lower in transplant recipients than in healthy individuals at both 1 month (635 vs. 7685 BAU/mL; p < 0.0001) and 6 months (1146 vs. 3277 BAU/mL; p = 0.0057) post third dose. Similarly, transplant recipients had lower antibody avidity than healthy individuals after the third dose, with geometric mean AI80 values of 4.5 M vs. 5.5 M at 1 month (p < 0.0001) and 4.6 M vs. 5.4 M at 6 months (p < 0.0001). Age, sex, and vaccine manufacturer may further influence humoral immune responses in the transplant cohort. Conclusions: Vaccine-induced humoral immunity varies across autoimmune, IBD, and transplant cohorts, with the most persistent impairment observed in transplant recipients across vaccine dose groups and at both post-vaccination time points. These findings reveal immune response patterns that may guide future studies evaluating vaccination schedules, immune monitoring, and clinical outcomes in these populations.

Vaccines doi: 10.3390/vaccines14080687

Authors: Xueyang Zeng Xiaoshan Yu Qiufen Zhang Biao Rong Moliang Chen Huanyang Qi Xulian Cai Tingting Qiu Yang Feng Shoujie Huang Huirong Pan Lishan Ye

Background/Objectives: The potential of vaccines to trigger autoimmune diseases (ADs) has been extensively investigated and remains a routine focus of vaccine-safety research. This post-marketing, real-world study compared the risk of ADs between females who received bivalent human papillomavirus (HPV) vaccine (Cecolin) and unvaccinated females. Methods: Eligible females aged 9–45 years registered in the Xiamen Health and Medical Big Data Center from September 2020 to December 2023 (post-Cecolin period) were enrolled. Cecolin recipients constituted the exposed cohort, and a matched unexposed cohort was generated in a 1:4 ratio based on age and calendar year. Case validation was conducted to determine optimal identification algorithms. Incidence rates (IRs) were calculated and incidence rate ratios (IRRs) with 95% confidence intervals (CIs) were derived from zero-inflated Poisson regression. Results: Overall incidence of ADs was 70.63 per 100,000 person-years (95% CI: 67.59–73.77) in the post-Cecolin period. Compared with matched unexposed cohorts, vaccinated females showed a significantly lower AD risk in both contemporaneously matched (IRR = 0.23, 95% CI: 0.08–0.65; p = 0.006) and historically matched (IRR = 0.21, 95% CI: 0.07–0.66; p = 0.008) analyses. Conclusions: Consistent with prior evidence, this study provides real-world evidence further confirming that Cecolin vaccination does not increase the risk of ADs. It adds the first large-scale post-marketing safety evidence for this Chinese domestic bivalent HPV vaccine, filling a critical evidence gap. These results may inform vaccination policy and guide post-licensure safety monitoring in China and other countries that have introduced this vaccine.

Vaccines doi: 10.3390/vaccines14080686

Authors: Monika Tokarczyk-Kloc Julia Ciecierska Robert Marguła Katarzyna Herbetko Bohdan Shmorhun Leszek Szenborn Mateusz Sokolski Kamila Maria Ludwikowska

Patients undergoing cardiac surgery are particularly vulnerable to infectious diseases, which may adversely affect perioperative outcomes and long-term prognosis both before and after the procedure. Moreover, those requiring heart transplantation must take immunosuppressive medications, further compromising their immunity. This narrative review aims to look for the sources of increased risk for infections as well as synthesize vaccination recommendations for these patient groups based on the available literature and guidelines. We considered the influence of age, comorbidities, length of hospitalization, procedure-related risks, and blood product transfusions on the increased risk of vaccine-preventable diseases. By comprehensively addressing these factors, healthcare providers can develop tailored vaccination strategies that maximize protection for cardiac surgical patients while minimizing potential complications and optimizing overall health outcomes.

Vaccines doi: 10.3390/vaccines14080685

Authors: Qing Zhang Quanman Hu Yaming Wei Jun Li Shuaiyin Chen

Background/Objectives: Dementia represents a major global health challenge, and preventive strategies remain limited. Observational studies have suggested a possible association between herpes zoster vaccination (HZV) and dementia risk, although the influence of vaccine type and dose regimen remains unclear. Methods: PubMed, Embase, and Web of Science were searched through January 2026. The primary random-effects meta-analysis included one adjusted estimate per independent study or data-source cluster. Quasi-experimental and correlated secondary estimates were reported separately, and alternative-estimate and leave-one-out analyses retained independent statistical units. The protocol was registered in PROSPERO (CRD420261326042). Results: Fourteen reports representing 13 studies were included. HZV was associated with a lower dementia risk in the primary analysis of five independent data sources (ratio estimate = 0.72; 95% CI: 0.65–0.81; I2 = 97.1%), with similar sensitivity results (0.70–0.76). Two regression-discontinuity studies reported eligibility-associated absolute reductions in dementia diagnosis of 1.3 and 1.8 percentage points. Two direct vaccine comparisons favored the recombinant zoster vaccine (RZV; Shingrix) over the live attenuated vaccine (ZVL; Zostavax) (RMTL ratio = 0.83; 95% CI: 0.80–0.87; RR = 0.82; 95% CI: 0.69–0.98). The only direct dose comparison favored two or more RZV doses over one dose (RR = 0.81; 95% CI: 0.74–0.88). Active-comparator associations were generally attenuated, whereas age- and subtype-specific findings varied. These secondary findings were exploratory. Conclusions: HZV was associated with lower dementia risk in observational studies, with directionally consistent quasi-experimental findings. Direct evidence suggested potentially stronger inverse associations for RZV and complete vaccination, but was based on few independent data sources. Substantial heterogeneity and residual confounding preclude causal interpretation, and further prospective or randomized evidence is needed.

Vaccines doi: 10.3390/vaccines14080684

Authors: Marina Stukova Anna-Polina Shurygina Arman Muzhikyan Ekaterina Romanovskaya-Romanko Zhanna Buzitskaya Marina Shuklina Anastasia Pulkina Daria Shamakova Kirill Kryshen Mariia Sergeeva Dmitriy Lioznov

Introduction: The development of bivalent mucosal vaccines capable of providing protection against both influenza and SARS-CoV-2 is a major public health focus. While most COVID-19 vaccines target the spike (S) protein, the highly conserved nucleocapsid (N) protein represents a strategic target for cross-reactive, cell-mediated immunity. This study evaluates Corfluvec, an intranasal vaccine candidate based on an attenuated NS1-truncated influenza vector expressing a fragment of the SARS-CoV-2 N protein. Methods: Protective efficacy, including viral load and pathomorphological changes in the lungs and vessels, was evaluated in Syrian hamsters challenged with high and low doses of SARS-CoV-2 (lineage B.1.1). Cross-protective efficacy against homologous and heterologous influenza A strains (H1N1pdm09, H3N2, and A/PR/8/1934) was tested in a lethal murine model. Additionally, immunogenicity of Corfluvec applied via human-compatible delivery device was tested in cynomolgus macaques (Macaca fascicularis). Results: In Syrian hamsters, vaccination significantly reduced viral loads in the lungs and nasal turbinates. Histopathological analysis revealed a preservation of lung vascular integrity: vaccinated animals showed stable CD31 expression and controlled Ki-67 proliferative activity, accompanied by a marked reduction in vasculitis and perivascular edema compared to placebo controls. In mice, the vaccine provided 100% protection against homologous and heterologous influenza virus challenges. In macaques, the two-dose intranasal immunization was well-tolerated and induced significant systemic IgG and mucosal sIgA responses, alongside robust N-specific IFNγ+ T-cell activation. Conclusions: Corfluvec is a promising bivalent vaccine candidate that provides dual protection against influenza and COVID-19. Its ability to limit viral shedding from the upper respiratory tract and to mitigate SARS-CoV-2-induced pulmonary pathology, contributing to the preservation of lung vascular integrity, underscores the utility of mucosal immunization with Corfluvec as a valuable intranasal complement to current systemic vaccination strategies.

Vaccines doi: 10.3390/vaccines14080683

Authors: Binyue Xu Ningyu Wan Qing Wang Ningpei Bai Chunbei Zhou

Background: Timely hepatitis B vaccine birth-dose (HepBV-BD) vaccination is a cornerstone strategy for preventing mother-to-child transmission of hepatitis B virus (HBV). Although hepatitis B vaccination coverage in China has improved substantially, evidence regarding long-term district-level spatiotemporal inequalities in timely birth-dose vaccination remains limited, particularly in western China. This study assessed spatiotemporal disparities in hepatitis B vaccination coverage across Chongqing, China, from 2016 to 2025. Methods: This ecological descriptive study used district- and county-level vaccination surveillance data from the Chongqing Immunization Information Management System. Temporal trends in HepBV-BD, timely birth-dose (TBD), HepBV2, and HepBV3 coverage were analyzed. Regional disparities, interregional inequalities, and spatial clustering were assessed using Global Moran’s I and Local Indicators of Spatial Association (LISA). Results: All vaccination indicators improved substantially during the study period. TBD coverage increased from 81.9% to 95.4%, whereas HepBV3 coverage increased from 83.7% to 98.7%. TBD coverage was strongly positively associated with HepBV3 coverage(r = 0.95, p < 0.001). Mountainous ethnic minority regions consistently exhibited the lowest TBD coverage despite marked improvement over time. Absolute interregional inequality decreased from 30.8 to 8.4 percentage points. Although Global Moran’s I was not statistically significant, LISA analysis identified persistent localized low-coverage clusters in southeastern mountainous regions and emerging high–high clusters in northern Chongqing. Conclusions: Hepatitis B vaccination coverage in Chongqing improved markedly between 2016 and 2025, accompanied by declining geographic inequality. Nevertheless, persistent spatial inequities in timely birth-dose vaccination remained in mountainous ethnic minority areas. Continued monitoring of spatial inequalities, together with strengthened primary healthcare capacity, culturally tailored health education, and equitable resource allocation, may help support geographically targeted immunization strategies and accelerate progress toward the WHO goal of eliminating viral hepatitis as a public health threat by 2030.

Vaccines doi: 10.3390/vaccines14080682

Authors: Michael Y. Bian Reagan Stevens Ankit Mangla Devarati Mitra Nicholas G. Zaorsky Jeremy S. Bordeaux Luke D. Rothermel

Background/Objectives: Immune checkpoint inhibitors (ICIs) and other systemic therapies can extend the survival of many patients with advanced melanoma, renewing interest in complementary strategies for unresectable or metastatic disease. Therapeutic cancer vaccines represent a possible approach. Recent evidence suggests commercially available mRNA vaccines can sensitize tumors to ICIs, challenging prior assumptions about neoantigen presentation. Despite renewed public interest in personalized cancer vaccine development, the proliferation of narrative and scoping reviews has not been matched by systematic mechanistic synthesis—platforms investigated across the 2010s and 2020s have not been rigorously compared within a single article. Accordingly, this review focuses on major vaccine platforms and proposes a comparative framework for understanding therapeutic melanoma vaccine development and immunologic rationale. Methods: Melanoma vaccine clinical trials listed on ClinicalTrials.gov were identified from 2010 to 2025. Eligible studies were screened and included in a qualitative review evaluating trial characteristics, vaccine platforms, study design, and reported outcomes. Results: There is one active Phase III clinical trial for melanoma vaccines in the US. Key principles of melanoma vaccinology include adjuvant, antigen, and delivery platform selection. From 2010 to 2025, four vaccine candidates advanced to Phase III trials, two provided Phase III results for peer review, one trial is ongoing, and no vaccines have been FDA-approved. Inconsistent reporting of outcomes and a lack of published results limited comparability across studies, precluding formal meta-analysis. Conclusions: Therapeutic melanoma vaccine options remain limited by translational challenges in study design and reporting gaps. This review synthesizes contemporary clinical trial activity and immunologic principles to inform future research.

Vaccines doi: 10.3390/vaccines14080681

Authors: Lespek Kutumbetov Moldir Azanbekova Balzhan Myrzakhmetova Moldir Tuyskanova Aisulu Valieva Nuraiym Sarsenkulova Gulzhan Zhapparova Dias Muzarap Muratbay Mambetaliyev Sanat Kilibayev Kuandyk Zhugunissov

Background/Objectives: Mpox (formerly monkeypox) is a re-emerging global health threat. While current vaccines are injectable, oral vaccination offers a painless alternative, though the harsh gastrointestinal (GI) environment challenges live viral vaccines. This study evaluated the stability of orthopoxviruses under simulated GI conditions to assess the physicochemical feasibility of oral mpox immunization. Methods: Attenuated and virulent strains of vaccinia, cowpox, and camelpox viruses were exposed to simulated gastric (pH 1.0–2.0 and 3.0–4.0 with pepsin) and intestinal (pH 7.0–7.5) conditions at 37 °C for 180 min. Viral titers were determined via cell culture assays. The physicochemical protective efficacy of enteric-coated capsules was evaluated using standard dissolution testing parameters. Results: All orthopoxviruses were rapidly inactivated under highly acidic fasting conditions (pH 1.0–2.0). However, they exhibited high stability at pH 3.0–4.0 and 7.0–7.5, retaining approximately 20–30% of their initial infectivity after 180 min. Enteric-coated capsules successfully maintained shell integrity in simulated gastric fluids for over 3 h and dissolved completely under intestinal conditions within ~130 min, aligning with small intestine transit times. Conclusions: Orthopoxviruses possess sufficient intestinal stability to support the physicochemical feasibility of oral immunization, provided they are protected from gastric acidity. Enteric-coated capsules represent a highly suitable delivery system for the intestinal release of live orthopoxvirus-based candidates, warranting further in vivo preclinical evaluation.

Vaccines doi: 10.3390/vaccines14080680

Authors: Daniela Di Placido Antonio Ciaramella Antonella Riccomi Claudia Maria Trombetta Maria Dorrucci Francesca Farchi Roberto Giuseppetti Serena Marchi Nunzia Sanarico Patrizio Pezzotti Anna Rita Ciccaglione Emanuele Montomoli Catia Valdarchi Silvia Vendetti

Background: Seasonal influenza vaccination shows highly variable effectiveness across individuals, particularly in older adults, in whom age-related immune decline compromises protective responses. Methods: This study evaluated immune responses to the 2019/2020 quadrivalent influenza vaccine in 75 individuals aged 25–89 years. Influenza-specific antibody titers and virus-neutralizing activity were measured before and four weeks after vaccination, and participants were stratified as high or low responders. Results: We observed that older individuals exhibited increased frequencies of myeloid-derived suppressor cells (MDSCs) and activated regulatory T cells (Treg) expressing HLA-DR and CD38, consistent with enhanced immunosuppressive activity. Importantly, higher levels of these immunoregulatory populations correlated with poor vaccine responsiveness in both adult and older participants. Additionally, circulating T follicular regulatory (Tfr) cells were elevated in older participants and in low responders, whereas T follicular helper (Tfh) cells remained unchanged, resulting in an increased Tfr/Tfh ratio associated with impaired antibody production. However, when adjusting for possible confounders, most immunoregulatory subsets did not remain independently associated with responder status, except CD38+ Treg cells. Conclusions: These findings suggest that immunoregulatory networks, while essential for controlling chronic inflammation during aging, may limit vaccine-induced immunity. Identifying biomarkers such as MDSC frequency, activated Treg phenotype, and Tfr/Tfh balance may contribute to the identification of individuals with different levels of vaccine responsiveness and could help inform future personalized vaccination strategies.

Vaccines doi: 10.3390/vaccines14080679

Authors: Mark H. Rozenbaum Ahuva Averin Derek Weycker Rotem Lapidot Amanda Miles Maria J. Tort Jeffrey Vietri Alexander Lonshteyn Stephen I. Pelton

Background/Objectives: Pneumonia is a leading cause of hospitalization among children in the United States, with a disproportionate burden in certain racial, socioeconomic, and clinical subgroups. The 13-valent pneumococcal conjugate vaccine (PCV13), introduced in 2010, significantly reduced pneumococcal disease overall, but its effect on disparities in all-cause hospitalized pneumonia (AC-hPNA) remains unclear. This study evaluated changes in AC-hPNA rates by age, race, comorbidity profile, and household income (HHI) before and after PCV13 implementation. Methods: A retrospective cohort study using Optum’s de-identified Clinformatics® DataMart (2007–2019) included children < 18 years. Rates (per 100,000 person-years) and incidence rate ratios were calculated for four periods: pre-PCV13 (2008–2009), peri-PCV13 (2010–2012), post-PCV13#1 (2013–2016), and post-PCV13#2 (2017–2019). Analyses were stratified by age group and, within each, by race, comorbidity profile (low, at-risk), and HHI. Results: Among 10.1 million children, AC-hPNA rates declined by 51–57% from pre-PCV13 to post-PCV13#2 across all age groups, with the largest reductions in children aged <2 years. Declines occurred across all race, comorbidity, and HHI subgroups; however, rates remained several-fold higher among at-risk children. Persistent disparities were observed among Black children < 2 years, children aged 2–5 years with HHI < $50,000, and children aged 6–17 years with HHI of $50,000–$99,999. Conclusions: Substantial reductions in rates of pediatric AC-hPNA were observed in the period subsequent to the introduction of routine PCV13, yet residual disparities persist among children with comorbidities and select racial and income groups. Targeted strategies are needed to address these gaps.

Vaccines doi: 10.3390/vaccines14080678

Authors: Teodor Cristian Blidaru David Sinclair Petr Smejkal Yasmin Maor Ernest Kuchar Catherine Weil-Olivier Mariano Votta Luminița Vâlcea Valeriu Gheorghiță

Central and Eastern Europe (CEE) carries some of the widest immunisation gaps in Europe, and improving coverage there is often treated as a problem of access infrastructure. On 14 May 2026, a multi-stakeholder meeting hosted at the Romanian Parliament brought together around twenty-five speakers, among some fifty participants in all, from Romania, Poland, the Czech Republic, and Bulgaria, together with international contributors, to agree which barriers to vaccine confidence matter most in the region, which interventions are deliverable within 12 to 24 months, and how responsibility for them should be divided among stakeholders. This Perspective synthesises that discussion as a set of strategies for coverage. Meeting-derived priorities are set against published coverage and confidence data for the region and against the published intervention literature. We argue that the central problem across the region is eroded trust rather than missing information, because misinformation succeeds mainly where trust has already broken down, a process deepened by a historically conditioned, post-communist distrust of public institutions. The two recommendations carried most strongly, as both high in expected impact and achievable within 12 to 24 months, were continuing professional education for primary care on vaccine communication and the resourcing of locally trusted community figures, including health mediators working with marginalised populations. We then show how system-design reforms already demonstrated in the region, in particular pharmacy-based vaccination, direct reimbursement, and targeted outreach to under-vaccinated and marginalised groups, turn restored confidence into measurable coverage while narrowing inequities. We close with a 12-to-24-month agenda for CEE, organised around a clear multi-stakeholder division of labour. These are stakeholder-derived priorities that now require implementation and evaluation.

Vaccines doi: 10.3390/vaccines14080677

Authors: Yanely Pineiro Puebla Helen Nicholls David Fitz-Patrick Lucy E. Horton Matthew W. Gawel Reynold Duarte Martinez Xingbin Wang Georgina Keep Xia Xu Emily Gomme Ingrid Scully Pirada Suphaphiphat Allen Kena A. Swanson Nadine Salisch Federico J. Mensa Ruben Rizzi Özlem Türeci Uğur Şahin Annaliesa S. Anderson Alejandra Gurtman Kelly A. Lindert

Background/Objectives: Vaccination remains an important means of protection against influenza and COVID-19. Administering influenza and COVID-19 vaccines as a combined formulation may be advantageous. Methods: This phase 3, randomized study evaluated an investigational combination nucleoside-modified messenger RNA (modRNA) vaccine formulated with monovalent XBB.1.5-adapted BNT162b2 vaccine (BNT162b2) and an investigational influenza modRNA vaccine (hereafter investigational combination modRNA vaccine); we report safety, tolerability, and immunogenicity of the investigational combination modRNA vaccine in healthy 18- to 64-year-olds in two cohorts (2 and 3). Results: In Cohort 2, 3127 participants received the investigational combination modRNA vaccine and 1563 received the concomitant licensed quadrivalent influenza vaccine (QIV) with BNT162b2. In Cohort 3, 1189 participants received the investigational combination modRNA vaccine, 605 received QIV, 607 received the investigational influenza modRNA vaccine, and 1191 received BNT162b2. Prespecified noninferiority criteria of the geometric mean ratio of strain-specific hemagglutination inhibition (HAI) or SARS-CoV-2 Omicron XBB.1.5 neutralizing titers or differences in percentages of participants achieving HAI sero-conversion or Omicron XBB.1.5 seroresponse for investigational combination modRNA vaccine to concomitant QIV and BNT162b2 (or to QIV and BNT162b2 each administered alone in Cohort 3) were met for influenza A and SARS-CoV-2 Omicron XBB.1.5 strains but not for the influenza B strain. The investigational combination modRNA vaccine was well tolerated with an acceptable safety profile. Conclusions: The single-dose investigational combination influenza plus COVID-19 modRNA vaccine elicited robust immune responses against influenza A and SARS-CoV-2 with acceptable safety. Further work is required to optimize influenza B responses. The modRNA platform offers promise and potential advantages for vaccine development. ClinicalTrials.gov Identifier: NCT06178991 (approval date: 20 December 2023).

Vaccines doi: 10.3390/vaccines14080676

Authors: Mohamed Lounis Djihad Bencherit Mohamed Abed Zahia Ben Aissa Zahia Gaafazi

Background/Objectives: Cervical cancer (CC), mainly caused by human papillomavirus (HPV), is one of the major cancers threatening women’s health in Algeria. However, despite the existence of a cost-effective vaccine, it has not yet been introduced into the national vaccination program. Recent information indicated that its introduction will be imminent. Thus, the current study was conducted to evaluate the level of awareness and knowledge about CC and HPV among the Algerian population as well as its attitudes toward HPV vaccination. Methods: A cross-sectional survey was carried out between 4 November 2022 and 8 May 2023 using a self-administered questionnaire that was diffused through social media platforms. Results: A total of 414 participants were included in our sample, with the dominance of those aged 18 to 30 years old (74.6%), those with university education (75.8%), and those with a medium financial level (77.5%). A high level of awareness was reported (76.3%), especially among healthcare workers (98.4%, OR: 17.099, 95% CI: 2.294–127.476, sig. = 0.06), participants aged more than 30 years (87.6%, OR: 2.78, 95% CI: 1.313–5.883, sig. = 0.008), and females (85.1%, OR: 2.02, 95% CI: 1.15–3.548, sig. = 0.014). However, the level of knowledge did not follow, since less than a third (32.1%) of the participants only were aware of HPV, and multiple gaps were reported regarding its epidemiology and its prevention. Moreover, while 30.8% of the participants were willing to get the HPV vaccine, 40.5% were hesitant, and 27.7% were resistant. The causes of rejection/hesitancy included mainly complacency, vaccine refusal, and the lack of confidence in the vaccine. In addition, hesitant and reluctant participants have shown a low level of knowledge and a high score of conspiracy beliefs. Conclusions: These results provide new insights into knowledge and attitudes towards CC and HPV vaccination. It reported that despite the high level of awareness about CC, gaps of knowledge remain and vaccination hesitancy/reluctance is persistent. These results suggest the need for raising awareness particularly about HPV which will consequently help to increase HPV vaccine acceptance.

Vaccines doi: 10.3390/vaccines14080675

Authors: Zhen Lin Zegang Chen Lijiao Pei Yueyun Chen Zhenyu Ding

The authors would like to make the following corrections to this published paper [...]

Vaccines doi: 10.3390/vaccines14080674

Authors: Isabel Leroux-Roels Tracey A. Day Sofie Deleu Chelsea McLean Oscar Go Todd A. Davies Jeroen N. Stoop Monika Peeters Maria G. Pau Bart Spiessens Michal Sarnecki Keira A. Cohen

Acknowledgements [...]

Vaccines doi: 10.3390/vaccines14080673

Authors: Fani Ladomenou Ioanna-Andriana Psarra Despoina Gkentzi

Respiratory syncytial virus (RSV) remains a leading cause of severe lower respiratory tract infection in early infancy, with the highest burden concentrated in the first months of life. Two immunoprophylactic strategies—maternal RSVpreF vaccination and long-acting monoclonal antibodies—now offer effective early life protection, yet differ in biological mechanisms, operational requirements, and programmatic implications. Maternal vaccination induces high-quality neutralizing antibodies that are transferred transplacentally, providing immediate protection from birth and integrating efficiently into antenatal care platforms. However, its effectiveness is constrained by gestational timing, physiological antibody waning, and reduced protection when vaccination occurs shortly before delivery. Long-acting monoclonal antibodies, including nirsevimab and clesrovimab, bypass maternal immune variability and provide standardized, season-long protection across gestational ages, including preterm infants. Economic evaluations demonstrate that both strategies can be cost-effective, though their relative value depends on local epidemiology, pricing, and coverage patterns. Economic outcomes for monoclonal antibodies and maternal vaccination are highly context-dependent and influenced by regional RSV epidemiology, healthcare utilization, product pricing, and implementation capacity, rather than universally favoring one strategy over the other. Global equity considerations remain critical: disparities in antenatal care access, supply chain fragility, and pricing differentials may widen gaps between high- and low-income countries. Remaining evidence gaps—including long-term safety monitoring, durability of protection, viral evolution, and implementation challenges—underscore the need for continued research and careful integration of these tools into national immunization programs.

Vaccines doi: 10.3390/vaccines14080672

Authors: Seyyedehfatemeh Ghalibafan Mona Oraei Mohammadali Ashraf Ali R. Djalilian Pooja Bhat Hajirah N. Saeed

Vaccine-associated anterior uveitis (VAAU) is an uncommon ocular inflammatory phenotype reported after several vaccine platforms. It describes anterior segment inflammation occurring after vaccination when infectious, autoimmune, idiopathic, medication-related, and other possible causes have been reasonably excluded. The current literature indicates that post-vaccination uveitis is rare relative to the scale of immunization, although anterior uveitis is frequently reported among post-vaccination ocular inflammatory events. Evidence remains limited by reliance on case reports, case series, retrospective cohorts, and passive surveillance data, which restricts precise incidence estimation and causal interpretation. Accordingly, the available evidence primarily supports a temporal association rather than a confirmed causal relationship. Proposed mechanisms include innate immune activation, molecular mimicry, adjuvant- or formulation-related immune stimulation, bystander activation, delayed-type hypersensitivity, and host susceptibility related to prior uveitis, autoimmune disease, immune dysregulation, or genetic predisposition. Clinically, VAAU may present with redness, pain, photophobia, blurred vision, anterior chamber cells and flare, keratic precipitates, posterior synechiae, elevated intraocular pressure, vitritis, or cystoid macular edema. Most cases described in the literature are mild to moderate and improve with topical corticosteroids and cycloplegic therapy, whereas recurrent, severe, or treatment-intensive courses have been reported mainly in predisposed individuals. Future work should emphasize active surveillance, standardized phenotype-specific reporting, harmonized case definitions, and mechanistic studies to better define risk, recurrence patterns, and causality. Careful interpretation of suspected cases can support accurate diagnosis, patient counseling, and vaccine-safety monitoring without undermining clinically indicated immunization.

Vaccines doi: 10.3390/vaccines14080671

Authors: Hongzhe Lin Mingyue Chen Rong Xiang Yating Kang Yiwei Zhong Duan Ma Bin Wang

Background: DNA vaccines are widely used due to their low production cost, ease of large-scale manufacturing, and rapid responsiveness to emerging epidemics. However, their relatively modest immunogenicity in larger species often requires potent adjuvants to elicit robust protective responses. GM-CSF and Flt3L are two cytokine adjuvants targeting dendritic cells (DCs). Although their combination has been reported to augment immune responses, the mechanism underlying the complementary effects of a genetically fused GM-CSF-Flt3L adjuvant plasmid remains incompletely understood. Methods: We constructed a GM-CSF-Flt3L fusion adjuvant plasmid and compared it with single-adjuvant plasmids for their effects on innate, humoral, and cellular immunity, as well as protective efficacy against lethal homologous virus challenge. Results: Compared with single-adjuvant plasmids, GM-CSF-Flt3L synergistically promoted the maturation of bone marrow-derived dendritic cells (BMDCs) and activated draining lymph node DCs, differentially expanded DC subsets, and enhanced the recruitment of migratory DCs. This adjuvant significantly elevated hemagglutinin (HA)-specific serum IgG titers, hemagglutination inhibition (HI) titers, and the responses of T follicular helper (TFH) cells and germinal center B (GCB) cells, while also enhancing the capacity of HA-specific CD4+ and CD8+ T cells to secrete IFN-γ and TNF-α. Following lethal homologous virus challenge, the GM-CSF-Flt3L group exhibited markedly reduced lung viral loads and no significant pathological damage in lung tissues. Conclusions: These findings demonstrate that the GM-CSF-Flt3L fusion adjuvant complementarily enhances humoral and cellular immune responses induced by the influenza DNA vaccine and improves protective efficacy, highlighting its potential as an effective DNA vaccine adjuvant.

Vaccines doi: 10.3390/vaccines14080670

Authors: Asiye Burcu Kuş Adnan Barutçu Sena Kara Öncü

Background: Healthcare workers play a critical role in parental vaccine decision-making and the uptake of non-routine childhood vaccines. This study aimed to evaluate healthcare workers’ knowledge, attitudes and behaviors regarding non-routine childhood vaccines, including rotavirus, meningococcal, human papillomavirus (HPV) and influenza vaccines. Methods: This cross-sectional study was conducted between October 2025 and March 2026 among healthcare workers in Türkiye. Data were collected using a structured questionnaire and the Attitudes Towards Vaccine Scale (ATVS), distributed through convenience and snowball sampling methods. Results: A total of 345 healthcare workers participated in the study. Recommendation behaviors differed significantly according to vaccine type (p < 0.001). Rotavirus and meningococcal vaccines were more frequently recommended than HPV and influenza vaccines. Although influenza vaccine had the highest awareness rate, it demonstrated the lowest recommendation rate and the lowest support for inclusion in the national immunization schedule. Physicians had significantly higher knowledge levels and vaccination attitude scores than non-physician healthcare workers (p < 0.001). ATVS scores were positively correlated with recommendation behaviors (ρ = 0.35, p < 0.001) and self-vaccination tendency (ρ = 0.34, p < 0.001). In multivariable analyses, higher vaccination attitude scores independently predicted greater self-vaccination tendency (OR = 1.07, 95% CI: 1.04–1.11, p < 0.001). Cost was the most commonly reported barrier to vaccine implementation. Conclusions: Positive attitudes toward non-routine childhood vaccines among healthcare workers do not necessarily translate into consistent recommendation behaviors across all vaccine types. Strategies targeting healthcare worker education, equitable vaccine access and standardized vaccine counseling practices may improve uptake and recommendation of optional childhood vaccines in Türkiye.

Vaccines doi: 10.3390/vaccines14080669

Authors: Yeldos Myrzakhmetov Nurika Assanzhanova Sholpan Ryskeldinova Aigerim Mailybayeva Aigerim Sagymbayeva Yerken Kozhamkulov Ekaterina Yamanova Rassul Sidikhov Nurlan S. Kozhabergenov Bekbolat Usserbayev Kuanysh Zhekebekov Sergazy Nurabayev Kuandyk Zhugunissov Nurlan Akmyrzayev

Background: The simultaneous circulation of highly pathogenic avian influenza (HPAI) H5N8 (clade 2.3.4.4b) and virulent Newcastle disease virus (NDV) genotype VII creates a cumulative risk for the poultry industry, rendering monovalent vaccination insufficient. This study aimed to develop and evaluate a combined inactivated vaccine against AIV H5N8 and NDV genotype VII based on local endemic strains. Methods: The vaccine was formulated as a water-in-oil emulsion (30:70) using Montanide™ ISA 78 VG. Evaluation included physicochemical characterization, safety assessment in chickens, immunogenicity evaluation via the hemagglutination inhibition (HI) test, and protective efficacy following challenge with virulent isolates. Results: The formulation demonstrated high stability and complete safety without adverse reactions. By 28 days post-immunization, the vaccine induced a robust, balanced humoral response with antibody titers reaching 9.10 ± 0.23 log2 against NDV and 9.00 ± 0.26 log2 against AIV, indicating no antigenic interference. Upon challenge, the vaccinated group exhibited 100% clinical protection and survival, compared to 100% mortality in controls. Furthermore, vaccination significantly reduced viral shedding, limiting horizontal spread. Conclusions: The developed combined inactivated vaccine demonstrates high safety, stability, and protective efficacy. It represents a promising candidate for comprehensive specific prophylaxis in endemic regions, effectively limiting horizontal pathogen transmission and mitigating economic losses in poultry production.

Vaccines doi: 10.3390/vaccines14080668

Authors: Yerke Suleimenova Indira Karibayeva Shnara Svetlanova Nurzhamal Akhmadyar Dinagul Bayesheva Gulbanu Boranbayeva Ainur Ikhambayeva Saule Burkitbayeva Aida Bolatbek

Background/Objectives: Rotavirus remains a major cause of acute gastroenteritis among children under five years of age, particularly in regions with heterogeneous vaccine implementation. In Central Asia, differences in the timing and coverage of rotavirus vaccination may influence circulating genotype patterns, yet regional evidence remains fragmented. Methods: A systematic review and meta-analysis were conducted in accordance with PRISMA 2020 guidelines and registered in PROSPERO (CRD420251274198). Electronic databases (PubMed, Web of Science, ScienceDirect, and Google Scholar) were searched without date restrictions. Studies reporting laboratory-confirmed rotavirus infection and genotype distribution among children under five years in Central Asia were included. Random-effects meta-analysis of proportions was performed to estimate the pooled genotype proportions among rotavirus-positive children, with subgroup analyses comparing the before and after vaccine introduction periods. Results: Six studies (ten before vaccine introduction strata and four after vaccine introduction strata; N = 1713 rotavirus-positive children) were included. A significant decline in the G1P[8] genotype was observed following vaccine introduction, with pooled prevalence decreasing from 0.468 (95% CI: 0.363–0.577) to 0.068 (95% CI: 0.034–0.133) (p < 0.001). In contrast, G2P[4] increased from 0.134 to 0.485 (p < 0.001), while G9P[4] and G9P[8] also increased significantly. G3P[8] and mixed genotypes declined, whereas G4P[8], G12P[8], and untypable strains showed no statistically significant subgroup differences. Substantial heterogeneity was observed (I2 > 90%), and evidence certainty was very low for all genotype outcomes. Conclusions: The available evidence suggests that rotavirus genotype distribution among children under five in Central Asia may have changed after vaccine introduction, with lower pooled proportions of G1P[8] and higher proportions of selected heterotypic genotypes in after vaccine introduction strata. Strengthened molecular surveillance using standardized genotyping protocols is needed to determine whether these patterns represent sustained genotype replacement or temporal fluctuation. These estimates are based on a small, heterogeneous evidence base with very low certainty and should be considered hypothesis-generating rather than confirmatory of a causal vaccine effect.

Vaccines doi: 10.3390/vaccines14080667

Authors: Yukihiro Shibuya Miyu Sakai Hideyasu Kiyohara

Mycobacterium bovis Bacille Calmette–Guérin (BCG), the only licensed vaccine against tuberculosis, provides inconsistent protection against pulmonary tuberculosis, reflecting an incomplete understanding of how vaccine-induced immunity is organized within tissues. Emerging evidence indicates that the route of vaccination is not merely a technical variable but a critical determinant of immune programming. Whereas parenteral BCG primarily elicits systemic immune responses, mucosal delivery reprograms immunity at the respiratory interface by promoting localized trained innate immunity, tissue-resident memory T (TRM) cells, and early containment of infection. In this review, we propose an integrated framework of “immune layering,” in which protection emerges through the coordinated interactions of epithelial regulation, trained innate immunity, tissue-resident adaptive memory, regulatory homeostasis, and systemic immune support across spatial and temporal scales. Within this framework, trained innate immunity serves as an initial conditioning layer that shapes subsequent adaptive differentiation, whereas epithelial- and microbiota-associated regulatory networks establish the tissue context in which immune responses are initiated, organized, and maintained. Importantly, effective mucosal immunity depends on a dynamically regulated equilibrium rather than maximal immune activation. The dissociation between enhanced early pulmonary immune responses and limited long-term protection underscores the influence of tissue-specific regulatory constraints and environmental context on vaccine efficacy. This framework redefines correlates of protection by identifying the vaccination route and tissue-level immune organization as fundamental determinants of protective immunity, thereby providing a conceptual foundation for the rational development of next-generation mucosal tuberculosis vaccines.

Vaccines doi: 10.3390/vaccines14080666

Authors: Hanumantha Rao Paritala Luis Mier-y-Teran-Romero Ramya Natarajan Peter Adams Cassandra Spector Katherine Topf Ashwin Kadambi Julia A. Falvey Mark J. Lamias David P. Durham Kimberly Armstrong

Influenza remains a significant national health security threat, particularly for vulnerable populations, as existing control measures do not fully mitigate its impact. This gap in protection is especially pronounced early in a pandemic when a well-matched vaccine may not yet be available, as well as in populations unable to mount an optimal vaccine response. Clinical studies support pre-exposure prophylaxis (PrEP) therapeutics as a promising complementary strategy to reduce influenza transmission and disease severity, potentially easing the strain on healthcare systems during outbreaks. This manuscript outlines the Biomedical Advanced Research and Development Authority’s (BARDA’s) target product profile (TPP) for a long-acting influenza PrEP product, reviews the current development landscape, and models the potential impact of early PrEP product deployment using agent-based modeling in a synthetic population of 19.5 million people across pandemic scenarios resembling the 1918, 1968, and 2009 influenza pandemics. Simulations showed that early deployment of a 70%–effective PrEP reduced cumulative and peak infections, delayed the epidemic peak, and provided the greatest benefit in less transmissible pandemics; at 40–50% coverage, PrEP fully mitigated a 2009-like pandemic and substantially reduced transmission in 1918- and 1968-like scenarios. The TPP defines key characteristics of an effective PrEP option for seasonal and pandemic influenza that (1) demonstrates a strong safety and tolerability profile across all populations; (2) targets a direct-acting antiviral mechanism of action; (3) reduces the relative risk of symptomatic influenza infection by at least 70% in an unvaccinated population and (4) provides single-dose, season-long protection to optimize patient adherence. In this context, integrating PrEP into influenza prevention strategies could improve control of virus spread, strengthen protection for high-risk groups, and significantly reduce the overall public health impact of seasonal and pandemic influenza.

Vaccines doi: 10.3390/vaccines14080665

Authors: Marthe Bogne Penka Johanna C. Meyer Lubayna Khan Tshepiso Mbangiwa Benjamin M. Kagina Rudzani Muloiwa Ruth Stewart

Introduction: Storytelling is gaining interest as a potentially useful research and communication approach in health. However, there remains a huge gap in synthesized evidence in relation to its use in vaccination. We set out to map existing evidence on the use of storytelling in vaccination practice. Methods: This review was conducted in accordance with Joanna Briggs Institute methodology and PRISMA-ScR guidelines. Databases were searched for eligible studies using search strings in PubMed, Scopus, Academic Search Premier, Africa Wide Information, PsycINFO, ERIC, Cochrane Library, Web of Science Core Collection, and SciELO Citation Index via Web of Science. The gray literature was searched on Primo and Google Scholar. References from other sources were identified through a manual search using Google. Identified citations were uploaded into Covidence for screening and data extraction. Qualitative content analysis was used to summarize data in conceptual categories, including frequency counts. Results: Overall, 6236 studies were identified and imported into Covidence. Following removal of duplicates, 3804 studies were screened for title and abstract. 386 studies met eligibility criteria for full-text screening, which led to 110 included studies. Storytelling was used in immunization between 1997 and 2025 as a communication intervention (96/110 studies), research method (12/110 studies), and therapeutic approach (3/110 studies). Most studies originated from North America (67/110 studies), while six originated from Africa. Two-thirds of included studies (64/110 studies) were randomized controlled trials. Among the 62 studies reporting vaccine-related outcomes, 80.6% (50/62 studies) reported changes in one or more vaccine-related outcomes following exposure to storytelling interventions. The trustworthiness of these outcome findings is unknown. Reported changes were more frequently observed for cognitive, affective, and intentional outcomes than for behavioral outcomes such as vaccine uptake. Again, these findings have not been subject to critical appraisal. Conclusions: Storytelling is emerging as an adaptable approach with potential for addressing contextual vaccine challenges. Although several studies reported changes in cognitive, affective, and intentional outcomes, this scoping review cannot ascertain whether these changes were attributed to storytelling itself.

Vaccines doi: 10.3390/vaccines14080664

Authors: Sanit Thongsriratch Therdpong Thongseiratch Saratis Pairoh Puttichart Khantee

Background/Objectives: Vaccine-preventable disease may generate medico-legal disputes not only after an adverse event following immunization, but also when a clinician is alleged to have failed to mention, recommend, revisit, refer for, or document a clinically relevant vaccine. We examine this “unmentioned vaccine” problem while distinguishing existing law (lex lata) from proposed good practice (lex ferenda). Methods: We conducted a documented purposive narrative and comparative medico-legal review. PubMed/MEDLINE, PubMed Central, structured scholarly web searches, publicly accessible legal repositories, and official policy websites were searched from database inception through 21 July 2026 using combinations of vaccination, informed consent/refusal, failure to recommend or vaccinate, referral, documentation, negligence, causation, and LMIC terms. Authorities were selected for doctrinal relevance and jurisdictional contrast, with citation chaining. Results: In the selected jurisdictions, patient-centered disclosure of material risks and reasonable alternatives is recognized in differing forms. Vaccine-specific cases are sparse and fact-sensitive and do not establish a universal duty to recommend, refer, or revisit every vaccine. Provider recommendation influences uptake, but this behavioral evidence does not itself establish legal duty or causation, and direct empirical evidence linking counselling omissions to claims remains limited. We therefore present ADRR—assess, discuss and disclose, recommend or refer, and record and revisit—as proposed practice guidelines developed by the authors and presented in conceptual form, not as a validated legal or clinical standard. Conclusions: ADRR may support proportionate, system-level preparedness, especially in LMICs, but implementation must account for access, supply, workforce, financing, records, and legal context. Stakeholder co-design and empirical validation are required before routine adoption.

Vaccines doi: 10.3390/vaccines14080663

Authors: Madan Khatiwada Yu-Tan Chen Carine Dochez Peter Delputte

Background: Vaccine acceptance is a fundamental prerequisite for uptake, which may vary over time in response to contextual and vaccine-specific factors and major global disruption. This systematic review and meta-analysis evaluated global trends and determinants of vaccine acceptance between 2009 and 2024. Methods: A comprehensive literature search was conducted using pre-defined keywords and controlled vocabulary related to vaccination, vaccine acceptance or hesitancy, with a broad search strategy designed to capture global evidence across multiple vaccine categories and geographic settings. Studies restricted to high-risk groups or other specific sub-populations (e.g., healthcare workers) were excluded. Studies reporting vaccine acceptance outcomes were systematically identified and pooled estimates were calculated across vaccine categories, WHO regions, income groups, and pandemic periods. Temporal trends and interaction effects were assessed to evaluate changes in vaccine acceptance among different vaccines and before, during, and after the COVID-19 pandemic. Results: A total of 264 publications, including 650,772 participants from 97 countries, were included. Overall, pooled vaccine acceptance was 70.63% and remained relatively stable throughout the study period. Most studies originated from high-income countries, whereas low-income countries and the African region were underrepresented. Childhood vaccines demonstrated the highest pooled acceptance (80.26%), followed by HPV vaccines (66.48%), while influenza vaccines showed the lowest acceptance (52.00%). Childhood vaccine acceptance increased over time and during the COVID-19 period, whereas significant negative interaction trends were observed for HPV and influenza vaccines. Higher vaccine acceptance was observed in African and South-East Asian regions compared with Western Pacific and European regions. Acceptance also varied across income groups, with greater hesitancy generally observed in higher-income settings. Conclusions: Vaccine acceptance among the general population remained relatively stable globally between 2009 and 2024 but varied substantially by vaccine categories, geographic regions, and economic settings. These findings highlight the context-specific nature of vaccine acceptance and the need for harmonized measurement tools and stronger evidence from underrepresented regions to support equitable immunization strategies.

Vaccines doi: 10.3390/vaccines14080662

Authors: Emilia J. Fields Cynthia Davis Francisco Perez Suellen Hopfer

Background: Black adults are frequently portrayed as uniformly vaccine-hesitant, obscuring heterogeneity in the attitudes, beliefs, and decision-making processes that shape vaccine decisions. Methods: Guided by the socioecological and 5C frameworks, a latent profile analysis was conducted to identify distinct and meaningful profiles of vaccine decision-making among Black adults in South Central Los Angeles, a historically disinvested and medically underserved community (N = 203). Results: Three profiles emerged: Empowered and Engaged Trusters (52.0%), Unempowered and Unengaged Noncommitters (32.2%), and Empowered and Engaged Skeptics (15.8%). Subsequent analyses identified healthcare utilization, age, and voting affiliation as predictors of profile membership. Additionally, profile membership was associated with five vaccination outcomes in expected directions, with Trusters reporting higher vaccination intentions and past uptake than both Noncommitters and Skeptics. Conclusions: Study findings underscore the heterogeneity in vaccine decision-making among Black adults and offer insight into the within-group diversity in vaccine acceptance beyond hesitancy. Findings have implications for tailored interventions that maintain confidence, overcome apathy, and reduce skepticism to better promote vaccine acceptance and uptake in Black disinvested communities.

Vaccines doi: 10.3390/vaccines14080661

Authors: Kimberly McKeirnan Ilse Truter Teri-Lynne Fogarty

Background: An estimated 25 million children globally miss routine vaccinations each year, with 14.3 million classified as zero-dose and the majority residing in low- and lower-middle-income countries (LMICs). Pharmacies are recognised as accessible healthcare delivery points, yet their role in paediatric immunisation in LMICs is not well defined. This literature review sought to evaluate pharmacist-provided vaccination services for paediatric patients in LMICs. Methods: A systematic review was conducted following Cochrane and PRISMA guidelines. Five databases and grey literature were searched for articles published between January 2005 and June 2026. Studies were reviewed by multiple authors to reduce the risk of individual bias and included if they reported original research involving pharmacists in LMICs delivering vaccination-related services to children aged 12 years and under. For each study, items intended for extraction included country, pharmacy setting, specific vaccines administered, patient age range, and specific roles for the pharmacist in the vaccination administration process. The protocol for this systematic review was registered with the Nelson Mandela University Faculty of Health Sciences Postgraduate Studies Committee and the Research Ethics Committee for Humans (H23-HEA-PHA-007). Results: Of 162 identified records, four studies from Bangladesh, Ethiopia, India, and Jordan met inclusion criteria. No study described pharmacists routinely administering paediatric vaccines. Instead, findings focused on indirect involvement, system readiness, and public perception. Significant barriers included limited infrastructure, inadequate training, and lack of regulatory authority. Study results were limited by a lack of information published and inclusion of only articles available in English. Conclusions: Evidence on pharmacist-administered paediatric vaccinations in LMICs is scarce. Expanding pharmacist roles could improve access and reduce zero-dose prevalence, but would require policy support, infrastructure investment, and further implementation research.

Vaccines doi: 10.3390/vaccines14080660

Authors: Prabda Praphasiri Darunee Ditsungneon Anusak Kerdsin Sutthichai Nakphook Jiraphut Kittiwatanachod Kanlaya Sornwong Suriya Naosri Sarunpattori Khunarsa Ponthip Wirachwong Isariya Techatanawat Piengthong Narakorn Somchaiya Surichan Jorge Flores Laina D. Mercer Christina S. Polyak Bruce L. Innis Rama Raghunandan Chakrarat Pittayawonganon Sopon Iamsirithaworn Supakit Sirilak Kriengkrai Prasert

Background/Objectives: Waning immunity after primary COVID-19 vaccination supports evaluation of additional doses. HXP-GPOVac is an egg-based, inactivated Newcastle disease virus (NDV)-vectored vaccine expressing a prefusion-stabilized SARS-CoV-2 HexaPro spike antigen. We evaluated the safety, tolerability, and immunogenicity of a single additional 10 µg dose of HXP-GPOVac administered to adults previously primed with two doses of either HXP-GPOVac or BNT162b2. Methods: Study GPO NDV-HXP-S 203 was an open-label phase II extension enrolling adults (18–75 years) who previously completed a two-dose primary series in Study 202 with either HXP-GPOVac or BNT162b2 (Pfizer–BioNTech; Comirnaty). All participants received a single additional 10 µg intramuscular dose of HXP-GPOVac ≥ 6 months after their second primary dose. Solicited local/systemic adverse events (AEs) were recorded for 7 days, unsolicited AEs through Day 28, and serious AEs (SAEs) and adverse events of special interest (AESIs) throughout follow-up. Neutralizing antibody titers (pseudovirus 50% neutralization titer, NT50) and anti-spike IgG (BAU/mL) were assessed pre-dose (Day 1) and post-vaccination through 12 months; a predefined subset underwent IFN-γ and IL-5 ELISpot. SARS-CoV-2 infection during follow-up was assessed using anti-nucleocapsid (anti-N) IgG. Symptomatic COVID-19 was identified through symptom-reported, symptom-triggered RT-PCR testing; sequencing was performed when feasible. Results: All 219 participants received HXP-GPOVac (167 primed with HXP-GPOVac and 52 with BNT162b2). Any solicited local reaction occurred in 22.2% (37/167) of HXP-GPOVac-primed and 26.9% (14/52) of BNT162b2-primed participants; any solicited systemic reaction occurred in 10.8% (18/167) and 13.5% (7/52), respectively. No vaccine-related unsolicited AEs or AESIs were reported. Three deaths occurred during the 12-month follow-up; one (a sudden cardiac death in an HXP-GPOVac-primed participant) was assessed by the safety medical team as possibly related to vaccination, and two were assessed as not related. Neutralizing antibody GMTs increased from 46.33 at baseline to 1569.04 at Day 15 in HXP-GPOVac-primed participants and from 77.25 to 841.34 in BNT162b2-primed participants; corresponding SCRs were 78.8% and 76.9%. Anti-spike IgG GMCs increased from 48.79 to 1480.14 BAU/mL and from 194.48 to 1547.88 BAU/mL, respectively. Responses declined over time but remained above baseline through 12 months. In the cellular immunity subset, post-vaccination IFN-γ responses increased, with comparatively modest IL-5 responses and no pattern suggestive of Th2 predominance. Conclusions: A single additional dose of HXP-GPOVac administered ≥6 months after primary vaccination with HXP-GPOVac or BNT162b2 was generally well tolerated and elicited robust recall humoral responses, with supportive findings of cellular immunity. Trial registration: Thai Clinical Trials Registry, TCTR20230213001.

Vaccines doi: 10.3390/vaccines14080659

Authors: Muhammad Farid Mohammad Nadir Sahak Isaac Baffoe-Nyarko Amany Ghoniem Sharifuzamman Eman Elmahdy Quamrul Hasan Mohammed Osama Mere Palwasha Anwari

Background: Measles and rubella remain key indicators of immunization system performance and are central to the Immunization Agenda 2030 (IA2030). Disruptions caused by the COVID-19 pandemic have widened immunity gaps and accelerated resurgence of vaccine-preventable diseases across multiple regions. This study assesses progress toward measles and rubella elimination in the WHO Eastern Mediterranean Region (EMR) during 2023–2024. Methods: We conducted a retrospective descriptive analysis of measles and rubella surveillance data, WHO/UNICEF Estimates of National Immunization Coverage (WUENIC), and Joint Reporting Form (eJRF) data for all 22 EMR countries and territories. Key indicators included disease incidence, MCV1 and MCV2 coverage, surveillance performance metrics, and verified elimination status. Results: Regional measles incidence increased from 110.8 to 116.3 per million population, while rubella incidence more than doubled from 1.9 to 4.3 per million. Large outbreaks in Yemen, Iraq, and Afghanistan disproportionally drove regional trends. MCV1 coverage remained stable at approximately 80%, while MCV2 coverage increased marginally from 73% to 75%. Only nine of 22 countries achieved ≥95% coverage for both doses in 2024. Persistent zero-dose populations, high dropout rates, and ongoing immunity gaps sustained transmission across multiple settings. Conclusions: The EMR remains off track to achieve measles and rubella elimination by 2030. Accelerated, equity-focused efforts are urgently needed to strengthen routine immunization systems, reduce zero-dose population, enhance surveillance capacity, and improve outbreak response—particularly in fragile and conflicted-affected settings.

Vaccines doi: 10.3390/vaccines14080658

Authors: Zhangzhou Shen Qinqin Feng Fen Wang Houqiang Luo

Therapeutic cancer vaccines are designed to initiate tumor-specific immunity, yet their clinical success depends not only on antigen selection but also on the capacity to overcome the profoundly suppressive tumor microenvironment. Within tumors, abnormal vasculature, hypoxia, nutrient competition, acidic pH, and suppressive myeloid and stromal cells collectively constrain antigen presentation, T-cell priming, trafficking, and effector function, often converting otherwise immunogenic vaccination into an ineffective immune stimulus. Recent advances in neoantigen discovery, dendritic cell engineering, and nucleic acid-based vaccine platforms have improved the precision of antigen delivery, but these gains remain insufficient unless vaccine-induced responses can be sustained and executed within the hostile metabolic and immunologic landscape of the tumor niche. In this context, the tumor microenvironment is not merely a barrier to be overcome, but an active determinant of vaccine outcome that shapes immune editing, promotes exhaustion, and limits intratumoral expansion of cytotoxic lymphocytes. Accordingly, the most promising therapeutic strategies now combine vaccination with checkpoint blockade, radiotherapy, stromal remodeling, or metabolic reprogramming to recondition the tumor ecosystem and permit productive antitumor immunity. Here, we discuss how tumor microenvironmental constraints govern vaccine performance, review emerging platform technologies, and outline combinatorial strategies aimed at converting immune priming into durable tumor control.

Vaccines doi: 10.3390/vaccines14080657

Authors: Ateş Kara İhsan Ateş Sebahat Tekcan Seçil Uysal Yüksel Hakan Aydoğmuş Mine Durusu Tanrıöver Aykut Özdarendeli Erdogan Oz Muhammed Emin Demirkol

Background/Objectives: COVID-19 vaccines may be given without requiring a negative test or absence of symptoms; however, this recommendation needs further safety evaluation. This study aimed to compare the adverse events following immunization (AEFI) between PCR-positive (asymptomatic/mildly symptomatic) and PCR-negative individuals at the time of vaccination, with a secondary objective of comparing the two vaccines (TURKOVAC and CoronaVac). Methods: This descriptive study was a secondary analysis of phase III clinical trials. Individuals who were positive for SARS-CoV-2 PCR at the time of vaccination constituted the PCR(+) group and those who tested negative or became positive after the 4th day following vaccination constituted the PCR(−) group. Whether participants had a history of COVID-19 was not considered. Results: Data from 5207 individuals were analyzed. AEFIs were more frequent in the PCR(+) group than PCR(−) group: site pain (24.5% vs. 16.7%, p < 0.001), arm pain (9.5% vs. 7.8%, p = 0.008), headache (14.8% vs. 10.0%, p < 0.001), fatigue (14.5% vs. 8.9%, p < 0.001), myalgia (12.3% vs. 7.5%, p < 0.001), sore throat (11.9% vs. 8.1%, p < 0.001), cough (7.9%; 11.1% vs. 6.9%, p < 0.001). These AEFIs were more frequent in the PCR(+) group with both vaccine groups separately. The distribution of AEFIs over time followed similar patterns in PCR(+) and PCR(−) individuals. Local AEFIs were slightly more common with the TURKOVAC, systemic AEFIs with the CoronaVac. Conclusions: While AEFIs were more common among PCR(+) group, they were mild, tolerable, and easily manageable. Our results support the suggestion that routine PCR testing prior to vaccination may not be warranted solely to mitigate concerns about anticipated adverse events.

Vaccines doi: 10.3390/vaccines14080656

Authors: Malabika Bhowmik Tooba Momin Neelu Thakur Neeraj Singh Mrigendra Rajput

The innate immune system provides the first line of defense against invading pathogens and relies on tightly regulated mechanisms to initiate and resolve inflammatory responses. In addition to transcriptional control, post-transcriptional regulation of messenger RNA (mRNA) plays a critical role in determining the magnitude and duration of immune responses. Among those key regulators, the ZFP36 family of CCCH-type zinc-finger RNA-binding proteins, including ZFP36, ZFP36L1, and ZFP36L2, plays a central role in controlling the stability and translation of inflammatory, immune-related, and viral RNAs. This review focuses on the ZFP36 family of RNA-binding proteins and highlights their emerging roles in inflammation, immune cell development and differentiation, and antiviral immunity, with a particular focus on ZFP36L1 and ZFP36L2. Recent evidence has identified ZFP36L1 as a broad-spectrum antiviral factor that restricts multiple RNA viruses through distinct molecular mechanisms. A detailed understanding of the molecular mechanisms underlying ZFP36L1- and ZFP36L2-mediated antiviral activity and immune regulation will facilitate rational development of host-directed antiviral therapeutics and their strategic integration with vaccination strategies to limit viral replication, shedding, and transmission, thereby improving the control of emerging and re-emerging viral diseases.

Vaccines doi: 10.3390/vaccines14080655

Authors: Maria Michailou Maria Bitsori Kostas Stylianou Diamantis Kofteridis Evangelos Blevrakis Rozalia Dimitriou Maria Zacharioudaki Emmanouil Galanakis

Background: Despite the increased infection-related morbidity of patients with chronic kidney disease (CKD), their vaccination coverage is low. Cocooning strategy has not been adequately researched in this group. Our aim was to evaluate vaccination coverage of CKD pediatric and adult patients and their families. Methods: In this prospective, single-center study, we recorded the vaccination coverage of CKD pediatric and adult patients and their families who attend a tertiary University Hospital. Vaccination rates were calculated according to the national vaccination program. Vaccination of pediatric CKD patients was compared to a control group of healthy children. Results: The vaccination rate of 63 hemodialysis patients was low for influenza (61.9%), COVID-19 (79.4% primary, 3.2% booster doses), RSV (50%), herpes zoster (42.4%), hepatitis B (41.3%), Streptococcus pneumoniae (25.4%), tetanus–pertussis (3.2%), and HPV (0%). Their 30 underaged relatives had low vaccination rates for influenza (13.3%), DTaP/Tdap (80%), and Men B (50%), with adequate vaccination for other pathogens. The 53 children with CKD were poorly vaccinated for influenza (20.8%), COVID-19 (0%), Streptococcus pneumoniae (15.4%), Men B (30.2%), DTaP/Tdap (67.9%), MMR (78.8%) and VZV (86.5%), but their vaccination rates for influenza were significantly higher compared to controls. Their 108 adult relatives were inadequately vaccinated for influenza (27.8%), COVID-19 (1.9%), and Tdap (1.9%). Their 35 underaged relatives were poorly vaccinated for influenza (22.9%) and DTaP (80%). Conclusions: Vaccination coverage of CKD patients is suboptimal for vaccines particularly important for their condition and their family members are insufficiently informed about potential contribution to their protection by cocooning strategy.

Vaccines doi: 10.3390/vaccines14080654

Authors: Ashleigh Flowers Shaylen Foley Swati Saxena Sutapa Biswas Priya Ganeshkumar Purna Kurkure Upendra Kinjawadekar Sara Comstock Nina DaSilva Batista Meenu Anand

Background: India accounts for one-fifth of global cervical cancer deaths, yet Human Papillomavirus (HPV) vaccination coverage remains low despite the World Health Organization (WHO) recommendations to initiate vaccination at age 9. With the national HPV vaccination campaign in 2026 and its approval for integration into India’s Universal Immunization Programme (UIP), strengthening physician knowledge, beliefs, and confidence in recommending the vaccine is critical. Methods: In 2023, the American Cancer Society and Cancer Foundation of India catalyzed two national medical societies, the Federation of Obstetric and Gynaecological Societies of India and the Indian Academy of Pediatrics, to educate physicians on HPV vaccination using a train-the-trainer (ToT) model. A mixed-methods evaluation, using the RE-AIM Framework, included pre- and post-training surveys assessing changes in knowledge, beliefs, confidence, and intent, as well as monthly engagement surveys and project reports analyzed using descriptive and inferential statistics. A fidelity assessment evaluated consistency of training delivery. Twenty in-depth interviews explored physician reactions and implementation of learnings, analyzed using a rapid approach. Results: A total of 18,206 physicians were trained. The post-training respondent group demonstrated higher HPV vaccination knowledge scores and more favorable responses in confidence, beliefs, and intent than the pre-training respondent group. The fidelity assessment demonstrated consistent delivery overall, with some variability in role play facilitation. Interviews highlighted increased physician confidence, peer knowledge sharing, and community engagement following the training. Medical societies reported strong program adoption and plans for continued efforts. Conclusions: A ToT physician training cascaded through medical societies is a feasible strategy to prepare physicians to recommend the HPV vaccine and address parental concerns at scale.

Vaccines doi: 10.3390/vaccines14080653

Authors: Kate S. Rawlings Olga Kim Anne Huvos

Equity is fundamental to an effective pandemic vaccination response, yet the COVID-19 pandemic demonstrated how inequitable access, driven by purchasing power and delayed supply for low- and middle-income countries (LMICs), prolonged transmission and enabled viral evolution. The Pandemic Influenza Preparedness (PIP) Framework offers a model for providing timely and equitable access to pandemic influenza vaccines. Through legally binding advance supply agreements, the PIP Framework secures real-time access by the WHO to a proportion of global vaccine production and mandates allocation based on public health risk and need. In doing so, it addresses the two axes of inequity observed in previous pandemics—distribution and timeliness—by ensuring that affected populations that do not have access, irrespective of income status, are not at the back of the queue.

Vaccines doi: 10.3390/vaccines14080652

Authors: Godfrey Musuka Patrick Gad Iradukunda Malizgani Mhango Oscar Mano Roda Madziva Helena Herrera Noah Mataruse Tafadzwa Dzinamarira

Background: Missed and zero-dose children remain major barriers to polio eradication in settings affected by insecurity, poverty, weak health systems, and social exclusion. This narrative review synthesized evidence on how gender norms and related social determinants influence childhood polio vaccination in Afghanistan, Nigeria, Pakistan, and Sudan. Afghanistan and Pakistan remain the only countries with endemic wild poliovirus transmission, while northern Nigeria, especially areas affected by insurgency, and war-affected Sudan continue to report substantial numbers of polio zero-dose and under-immunized children, together with occasional reports of circulating vaccine-derived poliovirus. Methods: A comprehensive search of peer-reviewed and institutional literature was conducted in major databases and relevant grey literature sources. Eligible studies examined childhood immunization or polio vaccination among children under five and reported gender-related determinants of vaccination uptake. Findings were synthesized thematically. Results: Forty-one studies were included. Five interconnected domains emerged: women’s empowerment, autonomy, and household decision-making; male involvement, household gender norms, and family power relations; socioeconomic and structural gender-related barriers; education, information access, community perceptions, and health system responsiveness; and war, insurgency and their gendered impact on childhood polio immunization. Across countries, limited maternal autonomy, restricted mobility, dependence on male decision-makers, poverty, conflict, displacement, misinformation, and weak health services reduced access to vaccination. Supportive male engagement, female health workers, trusted community leadership, and culturally responsive outreach facilitated vaccine acceptance. Conclusions: Gender influences childhood polio vaccination through intersecting household, community, structural, and health-system pathways. Family power extends beyond male decision-making, with women’s education and influence within households shaping vaccination decisions. Strengthening women’s agency, constructively engaging men (e.g., through husband schools), and delivering culturally responsive services are essential for reaching missed and zero-dose children and accelerating polio eradication.

Vaccines doi: 10.3390/vaccines14080651

Authors: Piotr Rzymski Małgorzata Wajdowicz Szymon Piaszczyński Piotr Czupryna Karolina Turzańska Monika Pazgan-Simon Paweł Skwara Justyna Hlebowicz Maciej Piaseck Dorota Zarębska-Michaluk Katarzyna Sikorska Robert Flisiak

Background/Objectives: SARS-CoV-2, influenza viruses, and respiratory syncytial virus (RSV) remain major causes of adult hospitalizations, but contemporary comparative data are limited. This study compared the epidemiological characteristics, clinical presentation, and outcomes of adults hospitalized with these infections during the 2025/2026 epidemic season in Poland. Methods: We conducted a retrospective multicenter study of consecutive adults hospitalized with laboratory-confirmed COVID-19, influenza, or RSV infection between September 2025 and April 2026. Demographic characteristics, comorbidities, vaccination status, clinical features, laboratory findings, and outcomes were analyzed. Independent predictors of in-hospital mortality were identified using multivariable logistic regression. Results: The study included 604 patients: 255 with COVID-19, 314 with influenza, and 35 with RSV infection. Distinct seasonal patterns were observed, with COVID-19 peaking in autumn, influenza in winter, and RSV in early spring. Most hospitalized patients were elderly and unvaccinated. RSV patients were older, more frequently affected by multimorbidity, ischemic heart disease, and cancer, and showed the greatest respiratory impairment, including the highest rates of hypoxemia and pneumonia. Influenza was characterized by more frequent fever, headache, and myalgia. Despite lower pneumonia rates, COVID-19 was associated with the highest in-hospital mortality (13.7%) and remained an independent predictor of death (aOR = 3.23, 95%CI: 1.68–6.22). Antibiotic use was common across all cohorts (62–77%). Conclusions: COVID-19 remained associated with the highest mortality among hospitalized adults, whereas RSV contributed substantially to respiratory morbidity in older individuals. These findings support improved vaccination uptake, continued surveillance, hospital preparedness, and antimicrobial stewardship.

Vaccines doi: 10.3390/vaccines14080650

Authors: Uğur Ergün Selma Tosun Ayşegül Seremet Keskin Ebru Demiray Gürbüz İrem Çiftci Sinem Ayaz İrem Aşkın Yılmaz Şenol Çomoğlu Işıl Deniz Alıravcı Funda Şahin Ahmet Şahin Vahibe Aydın Sarıkaya Özlem Türkmen Recen Derya Seyman Zeynep Türe Yüce Beyza Arpacı Saylar Emre Bayhan Alev Çetin Duran Ayşın Zeytinoğlu Müge Toygar Deniz Fatma Mutlu Sarıgüzel Sevil Öztaş Emine Çelik Tellioğlu Ömür Mustafa Parkan Zafer Adıgüzel Rasih Felek Ayşe İnci Hasan Bozdağ Şebnem Çalık Ayşe Deniz Yüksel Nagehan Didem Sarı Rasih İmran Tan İlyas Dökmetaş Fatma Yılmaz Karadağ Derya Öztürk Engin Selçuk Kaya

Objective: Varicella zoster virus (VZV), a member of the Herpesviridae family, is known as the causative agent of chickenpox (varicella). Following primary infection, VZV can remain latent for life and may reactivate over time to cause herpes zoster (shingles). Advanced age, immunodeficiency, and certain chronic illnesses are major risk factors for the development of herpes zoster. To prevent herpes zoster, a live zoster vaccine was licensed in 2006, followed by a recombinant zoster vaccine with higher efficacy in 2018. In Türkiye, the recombinant zoster vaccine was licensed in 2024. Raising awareness among healthcare workers is important both for their own health and the safety of vulnerable patients. This study aimed to evaluate healthcare workers’ knowledge and awareness of herpes zoster infection and zoster vaccines across the country, as well as to determine the prevalence of prior herpes zoster infection among them. Methods: After obtaining ethical approval, a nationwide multicenter survey was conducted. A questionnaire was distributed to healthcare workers via an online link. Participation was entirely voluntary. The survey collected demographic information (age, sex, profession, years of experience) and included questions on knowledge of herpes zoster, history of zoster infection, symptoms and severity (if applicable), awareness of the zoster vaccine, and vaccination attitudes. Results: A total of 5180 healthcare workers participated, of whom 3505 were female. The participants ranged in age from 18 to 79 years (mean age: 34.24 ± 11.52). Regarding professions: 47.9% were physicians, 21.3% were nurses or midwives, 0.8% were dentists or dental technicians, and 30% were from other healthcare professions. Among participants, 54.4% had ≤10 years of professional experience, 20% had comorbidities, and 10.5% were using immunosuppressive medications. It was found that 9.6% had previously had herpes zoster, 8.8% had no knowledge of the disease, 39.6% were aware of the vaccine, and 20.1% were unwilling to pay for vaccination. Multivariate binary logistic regression analysis revealed that being a physician significantly increased the likelihood of having correct knowledge by 1.961 times compared to other professions (p < 0.001, CI: 1.608–2.392). Similarly, those who had heard of herpes zoster were 3.191 times more likely to answer correctly than those who had not (p = 0.011, CI: 1.650–6.172). Male gender was significantly associated with a lower likelihood of having accurate knowledge compared to females (p = 0.001, OR = 0.720, CI: 0.594–0.874). Conclusions: This study revealed that healthcare workers’ knowledge and awareness regarding herpes zoster and its vaccines are generally insufficient. The recent licensing of the vaccine in Türkiye may explain this, but it is critical for healthcare professionals to be more informed about risk groups and vaccination indications in order to enhance the effectiveness of preventive healthcare services. Given the potential for serious complications of herpes zoster in elderly and immunocompromised individuals, the importance of vaccination should be emphasized more strongly to healthcare workers. Furthermore, the finding that 20.1% of those aware of the vaccine were deterred by its cost highlights the need to improve vaccine accessibility. Economic barriers preventing healthcare workers from being vaccinated emphasize the importance of making the vaccine widely available through public support to protect both healthcare workers and patient safety.

Vaccines doi: 10.3390/vaccines14080649

Authors: Udara Rathnayake Ruvindu Perera Palmy R. R. Jesudhasan Adnan Alrubaye

Bacterial chondronecrosis with osteomyelitis (BCO) is a major cause of lameness in modern broiler chickens. It remains a persistent challenge in the broiler industry, resulting in substantial economic losses and serious animal health concerns. The pathogenesis of BCO involves rapid muscle growth, resulting in disproportionate body weight relative to skeletal maturity, thereby increasing mechanical stress and leading to microfractures and osteochondrotic clefts in the proximal growth plates of the femora and tibiae. Infection progresses via hematogenous dissemination and colonization of the leg bones by opportunistic pathogens, primarily Staphylococcus spp., Enterococcus spp., and Escherichia coli, originating from the gastrointestinal or respiratory tract, leading to chronic inflammation, ischemia, biofilm formation, and progressive bone necrosis. Control strategies, including selective breeding, enhanced management and production practices, nutritional interventions, and the administration of antimicrobial agents, offer partial mitigation but have failed to provide a permanent solution to BCO incidence. Vaccination is one of the most promising and targeted immunological approaches to enhance the host immune responses against bacterial pathogens. Electron beam (eBeam) inactivated vaccines represent a significant advancement among available vaccination strategies. This review leverages current knowledge of the etiology, pathophysiology, control measures, and the use of eBeam technology (EBT) in vaccine development to provide a scientifically grounded and innovative approach to controlling BCO-associated lameness in broiler chickens. This article also provides insights into future directions for integrated, antibiotic-free strategies to mitigate BCO and revenue losses, enhance broiler welfare, ensure consumer safety, and support the long-term sustainability of the global poultry industry.

Vaccines doi: 10.3390/vaccines14080648

Authors: Maya Alkhidir Kannan Sridharan

Background: People living with human immunodeficiency virus (HIV) (PLWH) remain at increased risk of severe COVID-19 outcomes; however, conflicting evidence exists regarding the seroconversion rates of COVID-19 vaccines in this population. Methods: A systematic review and meta-analysis were conducted on studies reporting seroconversion outcomes following COVID-19 vaccination in PLWH. Results: Forty-four studies (5391 PLWH) were included in the meta-analysis. The overall pooled seroconversion proportion was 93.5%. Bootstrap analysis confirmed robustness (92.8%). Subgroup analyses revealed significantly higher seroconversion rates for mRNA vaccines (98.2%) compared to non-mRNA vaccines (80.5%). CD4 count demonstrated a graded association: <200 cells/mm3 (53.8%), 200–500 cells/mm3 (86.2%), and >500 cells/mm3 (93.5%). Prior COVID-19 infection (99.1% vs. 89.5%) and antiretroviral therapy (ART) status (93.5% vs. 49.6%) were significant determinants. Safety data demonstrated a favorable profile, with predominantly mild-to-moderate local (injection-site pain: 23.8%) and systemic (headache: 12.95%, fatigue: 6.4%) adverse events; serious adverse events were rare and no consistent association with HIV disease progression was observed. Conclusions: COVID-19 vaccination induces high seroconversion rates in PLWH, particularly among those receiving mRNA vaccines, with preserved CD4 counts, on ART, or with prior infection.

Vaccines doi: 10.3390/vaccines14080647

Authors: Denis Omara Christian Ndekezi Susan Mugaba Angella Nakyanzi Fortunate Natwijuka Anne Kapaata Frank Kato Drake Byamukama David E. Ggwaabya Orla Mugulusi Freddie Bwanga David P. Katete Enock Matovu Joseph Olobo Ekii Andrew Obuku Obondo James Sande Jennifer Serwanga Stephen Cose Pontiano Kaleebu Sheila N. Balinda

Background: Adenoviral vectors are widely used in vaccine development; however, pre-existing immunity to common human adenovirus serotypes can limit their effectiveness. Canine adenovirus type 2 (CAV-2) is a non-human adenovirus with low seroprevalence in humans, making it a suitable alternative vector. Despite its promise, comprehensive preclinical safety data for CAV-2 vector-based vaccine platforms remain limited. In this study, we evaluated the safety profile of a replication-defective CAV-2 vector expressing the Omicron BA.4 SARS-CoV-2 spike immunogen in BALB/c mouse models. Methods: The SARS-CoV-2 CAV-2 vector-based vaccine was expressed and propagated in AD293 cells. The mice received intramuscular prime-boost immunisations with low (1 × 106 PFU), moderate (0.5 × 1010 PFU), or high (1 × 1010 PFU) vaccine doses, alongside empty CAV-2 vector and physiological buffer control groups, and were monitored longitudinally up to Day 72. The mice were clinically assessed at days 0, 7, 21, 42, and 72 for any deviations from normal conditions in comparison to the control groups. Biochemical analyses were performed to evaluate liver and kidney function, as well as any tissue injury due to the vaccine candidate. Hematological parameters were assessed by conducting complete blood counts. Body temperature and weight changes were also monitored as an indicator of systemic toxicity. Results: The biochemical and haematological parameters remained within physiological reference ranges across all dose groups and timepoints, with no dose-related deviations, indicating that the vaccine candidate did not show evidence of hepatotoxicity, nephrotoxicity, tissue or haematological toxicity. Body temperatures remained within normal physiological ranges following both prime and booster immunisations, and body weights increased normally across all groups as the animals grew throughout the study period without any abnormal weight gain or loss. Conclusions: These results suggest that the replication-defective CAV-2-vectored SARS-CoV-2 vaccine candidate was well tolerated and did not demonstrate evidence of systemic toxicity under the conditions tested. These findings demonstrate that the CAV-2 vector exhibits a favourable safety profile in murine models when used as a vaccine delivery platform, supporting its translational potential as an alternative adenoviral vector-based vaccine platform. Further studies incorporating additional safety endpoints, including histopathological, vector persistence and shedding evaluation, are warranted to support continued development of the platform.

Vaccines doi: 10.3390/vaccines14070646

Authors: Tianchi Yang Xingqiu Ying Xiaoqing Wu Junzhe Shao Lixia Ye Yumin Tao

Background/Objectives: 23-valent pneumococcal polysaccharide vaccine (PPV23) effectiveness against community-acquired pneumonia (CAP) remains controversial, with critical gaps in low-coverage settings and beyond 5 years post-vaccination. We estimated real-world PPV23 effectiveness against CAP hospitalization and characterized its duration among elderly adults in a low-coverage region. Methods: A multicenter matched case–control study was conducted across 14 hospitals in Eastern China (2018–2022). Cases were patients aged ≥60 years hospitalized with clinically diagnosed CAP. Up to three controls per case were matched on sex, age (±3 years), admission date (±5 days), hospital, and residential community. Conditional logistic regression estimated vaccine effectiveness (VE), adjusting for chronic comorbidities and healthcare utilization. Results: Among 6645 cases and 15,806 controls, 5-year PPV23 coverage was 2.14% (cases) and 2.76% (controls). PPV23 was associated with a 22.5% reduction in CAP hospitalization (adjusted VE = 22.5%, 95% CI: 4.1% to 37.3%). Protection was concentrated in non-severe CAP (adjusted VE = 25.7%, 95% CI: 7.0% to 40.7%), with no significant effect in severe CAP (adjusted VE = −11.7%, 95% CI: −115.1% to 42.0%). Extending the exposure window to 6 years yielded no significant VE (adjusted VE = 17.3%, 95% CI: −1.8% to 32.8%). Conclusions: PPV23 provides meaningful protection against CAP hospitalization in elderly adults in low-coverage settings, only for non-severe disease. Waning efficacy beyond 5 years supports revaccination at that interval.

Vaccines doi: 10.3390/vaccines14070645

Authors: Ningning Du Shuai Shao Yuanyuan Zhang Cheng Liu Yuanyuan Pang Hui Hang Liling Chen

Background: Influenza poses a serious threat to the health of older adults, and vaccination is a key strategy for prevention. As an economically developed city, Suzhou has a rapidly aging population, yet the influenza vaccination rate among older adults remains substantially lower than that in developed countries. There is an urgent need to understand the current vaccination status and its associated factors to inform future strategies for improving vaccination coverage. Objectives: To compare influenza- and vaccine-related knowledge, attitudes, practices, and information access channels between vaccinated and unvaccinated older adults (≥60 years) in Suzhou, and to identify factors associated with vaccination behavior in economically developed areas. Methods: A comparative cross-sectional survey was conducted from April to August 2024 across six districts or county-level cities randomly selected from Suzhou’s ten county-level administrative divisions. Participants were divided into vaccinated and unvaccinated groups based on their influenza vaccination status during the 2023–2024 influenza season. A two-stage sampling method was employed: the six districts were selected as primary sampling units; within each district, eligible older adults (aged ≥60 years) were randomly selected from two independent sampling frames—the vaccination information system for the vaccinated group and the basic public health service system for the unvaccinated group. Face-to-face structured interviews were conducted using a questionnaire consisting of four sections; data were entered using EpiData 13.1 and analyzed using SPSS 27.0. The χ2 test, t-test, and multivariable logistic regression were used for statistical analysis. Results: Among 4622 valid older adults (vaccinated: n = 2007; unvaccinated: n = 2615), the vaccinated group scored significantly higher on influenza-related knowledge (4.06 ± 2.21 vs. 3.16 ± 2.33, p < 0.001), vaccine-related knowledge (2.10 ± 1.18 vs. 0.67 ± 1.07, p < 0.001), and perceived influenza risk scores (2.72 ± 1.42 vs. 2.26 ± 1.64, p < 0.001). Vaccine safety and efficacy endorsement were also markedly higher among the vaccinated group (70.3% vs. 22.0%; 49.7% vs. 9.3%). Regarding information sources, the vaccinated group relied more on healthcare institutions (54.56% vs. 46.92%), whereas the unvaccinated group relied more on television (60.34% vs. 51.17%). Multivariable logistic regression revealed that awareness of the influenza vaccine (aOR = 9.151, 95%CI: 6.32–13.25), having a planned vaccination site (aOR = 2.66, 95%CI: 2.01–3.54), and perceiving the vaccine as safe (aOR = 1.81, 95%CI: 1.31–2.49) were positively associated with vaccination, while rural household registration (aOR = 0.76, 95%CI: 0.63–0.93), full-time employment (aOR = 0.41, 95%CI: 0.28–0.60), and hypertension (aOR = 0.79, 95%CI: 0.65–0.94) were inversely associated. Conclusions: Compared with the unvaccinated group, the vaccinated group demonstrated significantly better influenza- and vaccine-related knowledge, risk perception, and recognition of vaccine safety and efficacy, and relied more on healthcare institutions for information. Multivariable regression analysis identified awareness of the influenza vaccine as the strongest associated factor. These findings suggest that vaccination coverage could be improved by strengthening vaccine knowledge promotion through healthcare professionals and increasing awareness of vaccination policies that integrate medical insurance reimbursement.

Vaccines doi: 10.3390/vaccines14070644

Authors: Zachary C. Goecker Meghan C. Burke Yi Liu Yuri A. Mirokhin Sergey L. Sheetlin Guanghui Wang Dmitrii V. Tchekhovskoi Xiaoyu Yang Stephen E. Stein

Background/Objectives: Glycosylation can affect vaccine antigen structure and function, making site-specific glycan characterization relevant to antigen quality and comparability. However, quantitative approaches for comparing glycan microheterogeneity remain limited. This study evaluated the utility of the glycopeptide abundance distribution spectra framework for measuring similarity among site-specific glycosylation profiles in vaccines and antigen reference reagents across manufacturing conditions. Methods: Intact N-linked glycopeptides were characterized by nanoflow liquid chromatography–tandem mass spectrometry with stepped-energy fragmentation. Products included monovalent and quadrivalent influenza antigens produced in embryonated eggs, Madin–Darby canine kidney cells, or Spodoptera frugiperda cells, together with a SARS-CoV-2 spike vaccine produced in Spodoptera frugiperda cells and a Chinese hamster ovary cell-produced varicella-zoster virus glycoprotein E vaccine. Site-specific glycan distributions were represented as distribution spectra and compared using NIST MS Search software. Dot-product scores ranging from 0 to 999 quantified similarity. Results: Across measured glycosylation sites, distributions clustered into six recurrent classes. Similarity was high for replicate analyses, conserved influenza components across annual formulations, and matched components from different suppliers within the same production platform (similarity scores = 978, 961, and 960, respectively). Similarity was lower between sites within the same protein, between influenza strains, and between production sources (similarity scores = 554, 540, and 209, respectively). Among production-source comparisons, egg- and Madin–Darby canine kidney-derived profiles were most similar, and the overall ordering of glycosylation similarity was consistent with broad phylogenetic relatedness among production hosts. Conclusions: Distribution spectra-based similarity scoring of vaccine glycoproteins provides a quantitative, reusable approach for documenting site-specific glycosylation microheterogeneity. Using this method, we can conclude that production source is the dominant contributor to variation, whereas replicates, annual formulations, and suppliers within the same production platform are highly consistent.

Vaccines doi: 10.3390/vaccines14070643

Authors: Luciana T. Pasquel-Muñoz Ana Lucía Ramírez-Béjar Joaquín Eduardo Chávez Cano Kiara Camacho-Caballero José F. Parodi Fernando M. Runzer-Colmenares

Background/Objectives: Respiratory infections are a major cause of morbidity and mortality among older adults. However, vaccination coverage against respiratory pathogens remains suboptimal, particularly in rural and vulnerable populations. This study aimed to identify factors associated with respiratory vaccination uptake among older adults living in rural Amazonian communities in Peru. Methods: We conducted an observational, analytical, cross-sectional study using secondary data from the Amazon Frail Project. A total of 429 adults aged ≥60 years from rural and suburban communities in San Martín, Loreto, and Ucayali were included. Vaccination coverage for influenza, pneumococcal disease, pertussis, and COVID-19, as well as vaccine combinations, was assessed. Multiple linear and Poisson regression models with robust variance were used to identify associated factors. Results: Complete vaccination coverage was 42.89% for influenza, 23.08% for pneumococcal disease, 4.43% for pertussis, and 70.16% for COVID-19. Only 3.50% of participants had received all four respiratory vaccines. Higher educational attainment, multimorbidity, social frailty, greater muscle mass, better physical performance, and healthcare center attendance were associated with higher vaccination uptake. Depressive symptoms, cognitive impairment, functional dependency, physical frailty, dynapenia, and higher body mass index were associated with lower vaccination uptake. Conclusions: Respiratory vaccination coverage was suboptimal among older adults living in rural Amazonian communities. Educational, functional, physical, social, and healthcare access factors significantly influenced vaccine uptake, highlighting the need for targeted immunization strategies in vulnerable rural populations.

Vaccines doi: 10.3390/vaccines14070642

Authors: Anastasia Kovpak Sergey Pashkov Mariia Kostrova Kirill Nebesnyi Nikita Yakovlev Olga Polyakova Vladislav Vasilenko Lycheva Natalia Yury Ivin Anastasia Piniaeva Alexandra Siniugina Aydar Ishmukhametov

Objectives: Antiviral vaccines are usually created by inactivating viruses using physical or chemical methods. Inactivation of poliovirus with β-propiolactone (BPL) has advantages, including the absence of a requirement for long-term incubation with the inactivating agent, which minimizes the risk of negative effects of the potentially dangerous substance on the virus and reduces the duration of the inactivation process. Methods: BPL was applied at 0.2% (w/v) concentration under two conditions: 4 °C for 24 h and 37 °C for 3 h. Inactivation completeness was confirmed on Vero cell culture, while immunogenicity was assessed in guinea pigs via neutralizing antibody test. Conclusions: Two variants of virus inactivation made it possible to obtain inactivated samples that retained their immunogenic properties. BPL-inactivated samples retained sufficient D-antigen levels and elicited neutralizing antibodies comparable to or exceeding those from formaldehyde-inactivated controls. The inactivation method at 37 °C provided faster inactivation, while at 4 °C it provided a smooth decrease in virus titer. These results confirm that β-propiolactone is a viable alternative to formaldehyde for the production of inactivated polio vaccine (IPV), providing rapid inactivation of the virus compared to inactivation with formaldehyde while maintaining immunogenicity, as confirmed by guinea pig control.

Vaccines doi: 10.3390/vaccines14070641

Authors: Jisang Kim Mariusz Skwarczynski Rachel J. Stephenson

Boar taint is a persistent challenge in pork production, caused primarily by the accumulation of androstenone and skatole in adipose tissue. It affects 5–40% of uncastrated male pigs and is perceived negatively by a substantial proportion of consumers, with skatole detectable by almost all individuals. Traditional surgical castration effectively prevents boar taint but is increasingly criticized on animal welfare grounds. Immunocastration using gonadotropin-releasing hormone (GnRH) vaccines has emerged as a promising alternative, providing reversible suppression of reproductive function while maintaining growth efficiency. This review integrates current knowledge on the biochemical basis of boar taint, evaluates the performance of commercial vaccines such as Improvac® and GonaCon®, and examines economic, regulatory, and consumer factors influencing adoption. Immunocastration presents limitations due to variability in immune responses, the need for multiple doses, and challenges related to public perception. To address these challenges, intensive research is underway on single-dose formulations, precision adjuvants, and advanced delivery technologies, all of which are expected to drive the next generation of immunocastration vaccines.

Vaccines doi: 10.3390/vaccines14070640

Authors: Olga V. Masalova Ekaterina I. Lesnova Vyacheslav V. Kozlov Vladimir T. Valuev-Elliston Kristina Yu. Permyakova Natalya E. Fedorova Tatyana N. Nikolaeva Alexander V. Pronin Alexander V. Ivanov Alla A. Kushch

Global elimination of hepatitis C virus (HCV) infection requires not only direct-acting antivirals (DAAs) but also the development of a highly effective prophylactic and/or therapeutic vaccine. Background/Objectives: Our aim was to optimize the composition of the candidate vaccine against HCV by combining recombinant non-structural proteins and a DNA construct with a complex adjuvant. Methods: C57BL/6 and DBA/2J mice were immunized three times at 2-week intervals using different schemes. The viral antigens consisted of a mixture of NS3, NS5A, and NS5B proteins and/or recombinant DNA expressing NS3-NS5B polyprotein. As adjuvants, a complex adjuvant, a mixture of Polymuramil® and Pyrogenalum® (NOD1/NOD2 and TLR-4 agonists), or a CpG ODN adjuvant (TLR-9 agonist) were used. Results: The most efficient regimen was three subcutaneous administrations of the combined DNA, recombinant protein components, and a new complex adjuvant. This scheme elicited a robust immune response, characterized by high antibody titers, enhanced antigen-specific lymphocyte proliferation, and significant interferon-gamma (IFN-γ) secretion in both mouse lines. Furthermore, the complex adjuvant outperformed CpG ODN in stimulating both humoral and cellular immunity against the HCV antigens. The vaccine composition stimulated the formation of CD4+ memory T cells and decreased the relative frequences of suppressive Treg and MDSCs. Conclusions: The presented candidate vaccine induces a strong immune response to HCV proteins. The next step would be to validate the protective effect in cell culture and animal models. This would one the path to preclinical studies of this vaccine composition.

Vaccines doi: 10.3390/vaccines14070639

Authors: Devin B. Lowe Neda Feizi Walter J. Storkus

Immunotherapies integrating immune checkpoint inhibitors (ICI) represent the current standard of care for many solid cancers, yet they effectively treat only a minority of patients due to intrinsic or acquired resistance mechanisms [...]

Vaccines doi: 10.3390/vaccines14070638

Authors: Balzhan N. Tatibekova Daniel Yakubovich Ademi K. Sagatbayeva Aigul A. Ismailova

Background: Advances in neonatal intensive care in Kazakhstan have improved the survival of preterm infants, including those with very low birth weight (VLBW) and extremely low birth weight (ELBW). However, after hospital discharge, these medically vulnerable children may remain insufficiently protected against vaccine-preventable infections because of prolonged temporary medical exemptions, clinical caution, parental concerns, and fragmented coordination between specialized follow-up services and primary health care. Objective: This study aimed to assess vaccination coverage in a 10-year cohort of high-risk preterm infants and to identify clinical, parental, and organizational factors associated with delayed immunization. Methods: We conducted a retrospective cohort study of 331 high-risk preterm infants followed at a specialized pediatric center in Astana, Kazakhstan, between 2015 and 2024. Vaccination status at hospital discharge and at 24 months of chronological age, documented temporary medical exemptions, reasons for delayed or missed vaccination, and confirmed cases of pertussis and measles were analyzed. A supplementary cross-sectional survey of parents, physicians, and health care managers was conducted to further explore barriers to catch-up immunization. Results: At hospital discharge, 259 infants (78.2%) had not received the BCG or hepatitis B vaccine. By 24 months of age, 34.1% (n = 113) were fully vaccinated according to age, whereas 49.8% (n = 165) remained completely unvaccinated. During the observation period, 30 cases of measles and 17 cases of pertussis were recorded within the cohort, primarily during nationwide outbreaks. Among the 10 children with a history of measles before 12 months of age, 2 developed subacute sclerosing panencephalitis (SSPE), 1 developed profound hearing loss, and 1 required prolonged oxygen therapy following pneumonia. In addition, 2 children with periventricular leukomalacia (PVL) experienced clinical deterioration, while 1 infant with pertussis required hospitalization during the acute phase of illness. Conclusion: High-risk preterm infants in this cohort experienced substantial and persistent gaps in immunization after hospital discharge. These findings underscore the importance of regular reassessment of temporary medical exemptions, improved coordination between specialized follow-up services and primary health care, and strengthened catch-up immunization strategies for medically vulnerable children.

Vaccines doi: 10.3390/vaccines14070637

Authors: Angeliki Irakleous Eleni Vergadi Despoina Gkentzi Eleftheria Hatzidaki

Background: Neonates and young infants are susceptible to vaccine-preventable diseases because of immature immune responses and delayed acquisition of vaccine-induced protection. As household members and caregivers are a major source of exposure, international organizations recommend cocooning, i.e., vaccination of susceptible individuals who are in regular contact with infants, to provide complementary indirect neonatal protection. To evaluate cocooning implementation, we assessed influenza and pertussis vaccination uptake among mothers and close contacts of hospitalized neonates and identified factors associated with vaccine uptake. Methods: Mothers of neonates hospitalized in a Neonatal Intensive Care Unit (NICU) between 1 January 2022 and 31 December 2024 were invited to complete a structured questionnaire. Mothers reported their own vaccination status and that of the neonate’s close contacts. Associations between maternal characteristics and vaccine uptake were examined using logistic regression. Results: In total, 405 mothers participated. Influenza vaccination uptake was 47.6% among mothers, and at least one adult close contact was vaccinated in 53.6% of families. Pertussis vaccination uptake was 40.5% among mothers, and at least one adult close contact was vaccinated in 32.3% of families. The most frequently reported reason for non-vaccination was low perceived need among unvaccinated mothers (74.1% for influenza and 83.4% for pertussis) and among families with incompletely vaccinated adult close contacts (81.8% for influenza and 89.7% for pertussis). In multivariable analyses, higher maternal education was associated with increased uptake of both influenza (OR 2.36, 95% CI: 1.47–3.80, p < 0.001) and pertussis vaccination (OR 4.25, 95% CI 2.02–8.94, p < 0.001), whereas younger maternal age (≤25 years) was associated with lower influenza vaccine acceptance (OR 0.24, 95% Cl: 0.1–0.60, p = 0.002). Conclusions: Vaccination uptake among mothers and adult close contacts of NICU-admitted neonates was suboptimal for both influenza and pertussis vaccines. Targeted counseling before delivery, reinforced during maternity or NICU hospitalization as a catch-up opportunity, and system-level implementation measures aligned with the dominant barrier of low perceived need are needed to strengthen cocooning in this high-risk population.

Vaccines doi: 10.3390/vaccines14070636

Authors: Shah Nawaz Jiskani Musa Khan Mohammed Osama Mere Wei Xia Atta Ur Rehman

Background: Despite noteworthy progress in the Expanded Program on Immunization (EPI) for improving vaccination coverage worldwide, inequalities in vaccine uptake and accessibility persist in several middle- and low-income states. Pakistan’s routine vaccination uptake varies greatly between federal geographical regions and continues to fall below the standard threshold needed to attain optimal herd immunity. The Federal Directorate of Immunization (FDI) in collaboration with the provincial Expanded Program on Immunizations implemented Enhanced Outreach Activities (EOAs) to boost immunization delivery in selected districts in order to address immunization coverage gaps in marginalized and difficult-to-reach communities. The purpose of this secondary data research was to evaluate whether EOAs improved immunization coverage in the country. Methods: The Federal Directorate of Immunization’s longitudinal panel analysis of district–month administrative data for the years 2011–2021 have been analyzed. The research investigation reviewed 158 districts’ monthly vaccination records for multiple antigens, covering regions where EOAs were successfully carried out in particular months. National and subnational analyses were carried out to measure geographical variations in the impact of Enhanced Outreach Activities (EOAs). The average vaccination coverage during EOAs and non-EOAs months was compared using the paired t-test. Results: An aggregate of 2430 months with EOAs were included in the analysis of 19,068 monthly district observations. National level analysis revealed higher average vaccinations during the EOA months for all antigens, but a statistically significant increase was observed for IPV and measles second dose (p < 0.05) only. Provincial-level results indicate that the impact was more evident in underserved regions. Khyber Pakhtunkhwa, Balochistan, Punjab, and Sindh demonstrated statistically significant increases in vaccination counts for most antigens. Due to variations in baseline population coverage, as well as health care sector capability, the extent of improvements differed throughout regions. Conclusions: In Pakistan, routine immunization counts has been improved via enhanced outreach initiatives, especially in provinces with lower initial vaccination rates and restricted accessibility to services. Strengthening outreach strategies, together with consistent fixed-site immunization services, is likely to accelerate progress toward equitable immunization coverage and contribute to achieving the Immunization Agenda 2030 goals.

Vaccines doi: 10.3390/vaccines14070635

Authors: Ravish Haradanahalli Shankaraiah Navyashree N. S. Divya Bharathi G. Trayambak Dutta Manish Mahajan

Background/Objectives: Rabies remains a lethal vaccine-preventable disease in India, and physicians managing animal-bite cases are central to effective post-exposure prophylaxis (PEP). With the increasing use of rabies monoclonal antibodies (RmAbs) as alternatives to conventional rabies immunoglobulins, this study assessed physicians’ knowledge, attitude, and practice (KAP) regarding rabies PEP, including RmAb awareness and acceptance. Methods: This multi-state, cross-sectional retrospective KAP survey was conducted among 208 physicians across ten Indian states using a structured, self-administered Google Form. The 33-item questionnaire assessed Knowledge, Attitude, and Practice domains, with 11 items each, scored binarily according to NCDC guidelines. Descriptive statistics, Shapiro–Wilk normality testing, Kruskal–Wallis tests with post hoc corrections, and Spearman rank-order correlations were performed. Results: Mean domain scores were 8.00/11 for Knowledge (72.7%), 7.22/11 for Attitude (65.6%), and 8.64/11 for Practice (78.5%). Key gaps were identified in the intramuscular pre-exposure prophylaxis schedule, management of excess RIG/RmAb after wound infiltration, exposure categorization of animal contact, and vaccine administration site in young children. The Knowledge–Practice correlation was moderately strong and statistically significant (r = 0.520, p < 0.001). Acceptance of RmAbs was high, with 88.5% recognizing them as effective replacements for RIGs and 84.6% considering them safer than RIGs. Practice scores showed the most consistent improvement, Knowledge scores improved on most items but declined sharply for the pre-exposure prophylaxis schedule, and Attitude scores showed a mixed pattern of gains and losses compared with the 2013 benchmark survey. Conclusions: Overall KAP scores were adequate, with Practice scoring highest. Targeted continuing medical education focused on NCDC guidelines and practical PEP scenarios is needed among physicians managing rabies exposures.

Vaccines doi: 10.3390/vaccines14070634

Authors: Bidhan Chandra Bera Manju Bernela Aashwina Madhwal Stephanie S. Pradhan Venkataramireddy Balena Taruna Anand Supriya Kandasamy Selvaraj Pavulraj Wandit Ahlawat Diksha Kandpal Priya Mor Gurmesh Bishnoi Nishant Vasdev Bhupendra Nath Tripathi Tarun Kumar Bhattacharya Nitin Virmani

Background: Equine herpesvirus type 1 (EHV-1) and equine influenza virus (EIV) are major respiratory pathogens in horses, causing significant economic losses in domesticated horses. Bacterial Artificial Chromosome (BAC) technology can be used to precisely manipulate the EHV-1 genome for the development of live-attenuated vector vaccines. Earlier, our group developed a live-attenuated EHV-1 vaccine by deleting virulence-associated genes using this technology and the mutant EHV-1 has been exploited for expressing foreign gene in the current study. Specifically, in this study, a mutant EHV-1 virus expressing the hemagglutinin (HA) gene of H3N8 EIV (sub-lineage: Florida clade 2) was generated and characterized in vitro. Methods: The HA gene of EIV (Florida clade 2) was used for antigen gene cloning. The expression cassette for the HA gene was commercially synthesized and inserted into the backbone of EHV1∆IR6 BAC using an En passant mutagenesis strategy. Recombinant clones were selected using antibiotic selection, PCR, and RFLP. Further, the recombinant virus was regenerated in RK-13 cells via transfection and characterized in vitro for plaque size, growth kinetics and immunofluorescence antibody test (IFAT). Results: PCR and RFLP confirmed the successful insertion of the HA gene into pEHV1∆IR6/gE BAC. The recombinant virus, vEHV1∆IR6/gE-HA(FC2), was successfully rescued in RK13 cells and demonstrated expression of the EIV haemagglutinin proteins by immunofluorescence assay. Although plaque size was reduced in the generated mutant virus in comparison to parental virus, the growth kinetics of the recombinant viruses were comparable to those of vEHV1∆IR6/gE. Conclusions: These findings demonstrate the successful expression of immunodominant hemagglutinin protein of EIV by recombinant EHV-1 and indicate the potential suitability of EHV-1 BAC as a vector platform for foreign gene expression.

Vaccines doi: 10.3390/vaccines14070633

Authors: Luca Giannella Andrea Ciavattini

The greatest challenge in human papillomavirus (HPV) vaccination is no longer scientific [...]

Vaccines doi: 10.3390/vaccines14070632

Authors: Jiayu Cai Zhuohang Liu You Zuo Yiu Wing KAM

Background: Men who have sex with men (MSM) experience a disproportionate burden of human papillomavirus (HPV)-related disease, yet vaccination uptake remains uneven. With MSM as the key population of interest, this review synthesized evidence on uptake, willingness, multilevel barriers and opportunities, and vaccine-oriented outcomes among MSM and related sexual and gender minority populations when MSM-relevant findings could be extracted. Methods: Six databases were searched for original English- or Chinese-language studies published from 1 January 2010 to 31 December 2025. Findings were synthesized narratively. Barriers and opportunities were mapped using a five-level socio-ecological model; study-level willingness–uptake patterns were explored using K-means clustering as an exploratory analysis among the nine studies reporting both outcomes; and genotype-specific and immunogenicity findings were summarized separately. Results: Fifty-three studies involving 169,241 participants were included; 87.2% of participants were MSM, and 79% of studies were cross-sectional. Barriers and opportunities occurred across individual, provider-related interpersonal, organizational/institutional, community, and policy/societal levels. Recurrent paired mechanisms involved knowledge and trust, provider recommendation and communication, service accessibility, community support, and eligibility and affordability. Nine studies contributed data to the exploratory clustering analysis; seven fell into low-uptake clusters, including three with high willingness but low uptake, which may indicate a possible study-level implementation gap. Two studies reporting genotype prevalence and antibody responses provided limited biological context supporting vaccination before exposure and suggesting potential benefit from catch-up vaccination. Discussion: Among MSM and related sexual and gender minority populations, HPV vaccination is shaped by interacting individual and structural conditions, with MSM remaining the principal focus of the evidence base. Improving uptake is likely to require complementary strategies: universal, gender-neutral routine vaccination in adolescence before their sexual debut, and targeted catch-up for MSM who missed routine vaccination, supported by trusted provider endorsement, convenient service delivery, community engagement, and inclusive, affordable policy. The thematic counts were study-level and unweighted, and the nine-study clustering analysis was exploratory rather than definitive.

Vaccines doi: 10.3390/vaccines14070631

Authors: Rui Liu Pengfei Deng Tian Yang Yun Pan Zhuoming Xu Laibao Yang Caoyi Xue Qizhang Wang

Background: Children with congenital heart disease (CHD) are highly vulnerable to influenza, yet real-world vaccine effectiveness (VE) data in this post-operative population are lacking, especially in China. This study estimated influenza VE against medically attended influenza-like illness (ILI) in post-operative children with CHD using inverse probability of treatment weighting (IPTW) to address confounding. Methods: We retrospectively enrolled 194 children who underwent CHD surgery in Shanghai (January–July 2023). Vaccination records were obtained from the Shanghai Immunization Information System, and ILI episodes were captured via structured interviews. The primary analysis used doubly robust quasi-Poisson regression on an IPTW pseudo-population. VE = (1 − RR) × 100%. Sensitivity analyses included multivariable Poisson regression, marginal structural models, and stabilized IPTW. Results: Vaccination coverage was 21.6% (42/194). After IPTW, all covariates were well-balanced (SMD < 0.10). The primary VE was 50.9% (95% CI: 11.0–72.9%). Sensitivity estimates ranged from 49.6% to 56.6%. Subgroup analyses showed consistently protective point estimates. Conclusions: Influenza vaccination provided moderate, robust protection (≈51% VE) against ILI in post-operative CHD children, comparable to healthy pediatric populations. Our results reinforce the urgent need to prioritize influenza immunization in this vulnerable group and offer critical baseline data for China.

Vaccines doi: 10.3390/vaccines14070630

Authors: Carolin Michael Matthias Bros Markus P. Radsak Hansjörg Schild Stephan Grabbe

Anthralin has a long history as a topical treatment for psoriasis, where it reduces keratinocyte hyper-proliferation and effectively clears plaques. While it lowers inflammatory markers in psoriatic skin, it paradoxically induces inflammation in healthy skin through reactive oxygen species (ROS) and related pathways. However, its precise mechanism of action remains incompletely understood. Interestingly, the once undesirable pro-inflammatory effect in healthy skin may now represent a valuable adjuvant property for transcutaneous immunization (TCI). In particular, combining anthralin with the TLR7 agonist imiquimod (IMQ) elicits strong cytotoxic T-cell responses in pre-clinical studies. When paired with antigenic peptides that can penetrate the skin, this immunization approach is especially promising in the context of cancer therapy, given the central role of cytotoxic T-cells in tumor rejection. However, current evidence is largely derived from mouse models, but its efficacy and safety in humans remain to be established. This review therefore examines whether anthralin can be repurposed as a cutaneous adjuvant for transcutaneous immunization, and which mechanistic and translational constraints must be overcome before human application.

Vaccines doi: 10.3390/vaccines14070629

Authors: Swetha Parvathaneni Jiro Sakai Lunhua Liu Mustafa Akkoyunlu

Neonates and infants exhibit fundamentally distinct immune responses compared to adults, resulting in increased susceptibility to infectious diseases and reduced vaccine efficacy. These age-specific responses are characterized by developmental constraints affecting both adaptive and innate immunity. T cell-independent (TI) responses to polysaccharide vaccines are severely impaired due to reduced transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI) expression on neonatal B cells, while T cell-dependent (TD) responses are compromised by Th2 bias in the CD4+ T cell compartment, and by restricted T follicular helper (Tfh) cell development. Emerging data suggest that cytokines such as IL-6 have completely opposite effects on Tfh cell development between adults and neonates. Germinal center (GC) B cell responses are further constrained by delayed follicular dendritic cell (FDC) maturation, impaired B cell receptor (BCR) signaling, and elevated frequencies of IL-10-producing regulatory B cells. The overall immunosuppressive phenotype associated with early age extends to the neonatal innate immune system as exhibited by altered dendritic cell (DC) subset distribution, decreased IL-12p70 production, lower expression of MHC class II and co-stimulatory molecules, and increased IL-10 secretion. To overcome these immune constraints, various adjuvants that are shown to enhance immune response to vaccines in adults are considered for early age vaccines. Although some of these adjuvants show promising results in animal experiments, mechanistic studies need to be conducted in detail since adult and neonatal in vivo environments may dictate different outcomes between the two age groups, especially because early-life adjuvant exposure may have long-lasting effects on immune system programming. Elucidation of age-specific immune responses to vaccines and adjuvants will help develop age-tailored strategies to develop safe and effective pediatric vaccines.

Vaccines doi: 10.3390/vaccines14070628

Authors: Andria Hadjikou Irene Heraclidou Alexandros Heraclides

Background: Vaccine hesitancy (VH) is a complex global public health threat requiring validated tools for its assessment globally. This study aimed to evaluate an extended adult Vaccine Hesitancy Scale (aVHS) among Greek-speaking adults. Methods: This study evaluated a newly developed extended version of a widely used aVHS, incorporating five additional items on long-term safety, risk–benefit evaluation, vaccine-related harm, scientific credibility, and perceived alternatives, on a cross-sectional sample of 491 adults in Greece and Cyprus. Cross-cultural adaptation of the extended aVHS involved translation, back-translation, and pilot testing. Structural validity was assessed using parallel analysis, exploratory factor analysis (EFA), and reliability using Cronbach’s α and McDonald’s ω. Criterion validity was assessed against focus-group classification using ROC analysis in 68 participants. Results: A one-factor EFA solution appeared the most parsimonious, showing strong loadings for the original and extended aVHS (0.67–0.86 and 0.65–0.87), with similar explained variance (60.31% and 60.06%). The one-factor solution was confirmed by parallel analysis for both scales. Internal consistency was excellent, and slightly higher for the extended than the original aVHS (α = 0.95; ω = 0.95 vs. α = 0.92; ω = 0.93). The five newly added items performed strongly, with item–rest correlations of 0.69–0.85 and loadings of 0.72–0.87. Criterion validity was excellent, with a slightly higher AUC (0.991 vs. 0.981) and numerically higher classification performance for the extended than the original aVHS. Conclusions: The extended aVHS is a psychometrically coherent tool that improves the performance of the original scale among Greek-speaking individuals. This scale may enhance VH surveillance, aiding targeted vaccination communication strategies.

Vaccines doi: 10.3390/vaccines14070627

Authors: Nicaise Ndembi Morenike O. Folayan Anthony Pilorget Nyanda E. Ntinginya Betty Mwesigwa Trevor A. Crowell Nyaradzo M. Mgodi Jerome H. Kim

The era of highly effective pre-exposure prophylaxis (PrEP) has transformed HIV prevention, yet global HIV incidence remains unacceptably high, particularly in sub-Saharan Africa. While antiretroviral-based prevention is critical, persistent structural barriers to access and adherence highlight the urgent need for a complementary preventive HIV vaccine. In this narrative review and perspective, we argue that scientific progress toward an HIV vaccine must be matched by equally ambitious preparedness investments across three domains: manufacturing and supply chains, clinical trial and regulatory infrastructure, and delivery systems and community engagement. Drawing on lessons from the global rollout of PrEP, post-exposure prophylaxis (PEP), and the COVID-19 pandemic response, we outline a five-pillar strategic roadmap. This roadmap focuses on ensuring that a future HIV vaccine reaches the people who need it most from the moment of regulatory authorization, calling for co-investment in diverse platforms, binding advance market commitments, logistical simulation, and proactive planning for post-licensure effectiveness trials. Preparedness is not secondary to science; it is its essential partner.

Vaccines doi: 10.3390/vaccines14070626

Authors: Nurika Assanzhanova Aigerim Sagymbayeva Gaukhar Shynybekova Kamshat Shorayeva Sholpan Ryskeldinova Aigerim Mailybayeva Yeldos Myrzakhmetov Ekaterina Yamanova Rassul Sidikhov Meiyrim Almezhanova Samat Zhaksylyk Zharkynai Absatova Kuandyk Zhugunissov Olga Chervyakova Nurlan Akmyrzayev

Background: Brucellosis remains a significant zoonotic infection affecting approximately 500,000 people worldwide annually, with no licensed human vaccine available. Recombinant influenza virus vectors expressing Brucella spp. antigens represent a promising vaccine platform. However, transitioning from laboratory constructs to clinical candidates requires validation of scalable purification methods compliant with Good Manufacturing Practice (GMP) standards. This study aimed to develop and optimize a pilot-scale purification protocol for these vectors. Methods: Recombinant influenza A viruses (H5N1) expressing Brucella spp. antigens (Omp16, Omp19, L7/L12, Cu-Zn SOD) were propagated in MDCK cell culture. The optimized purification process included: (1) clarification; (2) ultrafiltration/diafiltration (100 kDa MWCO); (3) two-step chromatography (anion-exchange Q-Sepharose® Fast Flow and multimodal Capto™ Core 700); and (4) sterile filtration. Process validation was performed across three independent pilot-scale batches (20 L each). Results: The purification process demonstrated high reproducibility for all constructs. Final preparations met established quality criteria: infectious titer ≥ 5.2 log10 TCID50/mL, hemagglutination activity 7.33 ± 0.58–8.33 ± 0.58 log2, total protein content 157–305 μg/mL, residual host cell DNA < 10 ng/dose, and bacterial endotoxin levels ≤ 0.15 IU/mL. The overall recovery of infectious virus was 20–24%, an optimal value for multi-stage bioprocessing. Preservation of the target genetic insert was confirmed in all final preparations by PCR and sequencing. Conclusions: The developed integrated purification protocol yields vectors with high purification efficiency, preserving biological activity and meeting regulatory quality requirements for residual host cell DNA and endotoxins. The technological platform demonstrated versatility, robustness (inter-batch coefficient of variation for yield did not exceed 10–12%), and scalability, establishing a foundation for preclinical and clinical studies of candidate brucellosis vaccines.

Vaccines doi: 10.3390/vaccines14070625

Authors: Willem Huisman Aart Mommen Stephanie Basten Kim Driessen Peter Pepels Qi Cao Hans Holtslag Melissa Ann Bourgeois Jacqueline Pearce

Background/Objectives: We describe the rationale, design and evaluation of a novel feline combination vaccine (Nobivac® NXT HCPChFeLV) incorporating RNA particle technology against feline leukemia virus (FeLV) alongside live attenuated components for feline herpesvirus-1 (FHV), feline calicivirus (FCV), feline panleukopenia (FPL) and Chlamydia felis. Efficacy and safety outcomes from laboratory and field studies are presented. Methods: Nobivac NXT HCPChFeLV is a 0.5 mL, non-adjuvanted, lyophilized vaccine containing live attenuated FHV, FCV, FPL, and C. felis strains, and an alphavirus replicon-derived RNA particle expressing FeLV envelope glycoprotein (gp85). The primary vaccination schedule involved subcutaneous vaccination at 8–9 weeks of age with a booster 4 weeks later. Onset-of-immunity studies were performed 1 week post primary vaccination. Duration-of-immunity studies evaluated challenge both at 1 year and 3 years after primary vaccination with a booster at 1 year (FHV, FCV, FeLV); FPL duration was assessed at 3 years after primary vaccination; C. felis duration was assessed at 1 year. Clinical signs of disease, survival, leukopenia (FPL) and pathogen excretion were assessed. Safety was assessed in laboratory overdose/repeat-dose studies and in a field study comparing concurrent (non-mixed) use with rabies vaccination vs a positive control regimen. Results: Vaccination significantly reduced clinical disease following FHV, FCV and C. felis challenge and reduced FHV-associated mortality. Vaccinated cats were protected from FPL clinical disease, mortality, leukopenia, and FPL excretion. Persistent FeLV antigenemia was significantly prevented after primary vaccination and in 1-year-duration-of-immunity studies and was reduced 3 years after revaccination. The excretion of FHV, FCV and C. felis was significantly reduced in vaccinates vs controls. No serious adverse events were observed in laboratory studies; field vaccination was well tolerated with no injection-site reactions reported. Conclusions: Nobivac NXT HCPChFeLV provides robust, long-lasting protection against multiple feline pathogens, reduced pathogen shedding and demonstrated a favorable safety profile, supporting its use in feline preventive healthcare.

Vaccines doi: 10.3390/vaccines14070624

Authors: Isadora Rodrigues Almeida Marcela Fermoselle de Vita Silva Taline de Brito Cavalcante Giovanna Alves de Britto Manuela Cândido Amaral dos Reis Luis Fernando Lima Bueno Luana dos Santos Ribeiro Gustavo Yano Callado Susana Cristina Aidé Viviani Fialho Antonio Braga Glória Calagna Edward Araujo Júnior

Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract infection in young infants and accounts for substantial morbidity, hospitalization, and mortality worldwide, with the highest burden concentrated in the first months of life, when immunological and anatomical immaturity favors severe disease. Maternal vaccination has emerged as a strategy to bridge this window of vulnerability through the transplacental transfer of neutralizing antibodies. This integrative review synthesizes scientific articles published between 2022 and 2026, including systematic reviews, meta-analyses, narrative reviews, and position statements from national and international scientific societies, addressing the epidemiology, clinical manifestations, diagnosis, mechanism of action, efficacy, safety, and public health impact of maternal RSV immunization. The bivalent prefusion F protein vaccine (RSVpreF; Abrysvo®), administered as a single intramuscular dose between 32 and 36 weeks of gestation, induces maternal IgG that is transferred to the fetus and confers passive protection during the first six months of life. In the phase 3 MATISSE trial, vaccination demonstrated 81.8% efficacy against severe RSV lower respiratory tract infection within 90 days of birth and 69.4% within 180 days, alongside reductions in hospitalization. The safety profile was favorable, with predominantly mild and transient adverse events; a numerical imbalance in preterm birth remains under surveillance and underlies the precautionary gestational window. Maternal vaccination and long-acting monoclonal antibodies (nirsevimab) are best regarded as complementary rather than competing strategies. Current evidence supports maternal immunization as one of the most effective measures to reduce the burden of RSV disease in early infancy.

Vaccines doi: 10.3390/vaccines14070623

Authors: Christelle Radi Jana Abu Faraj Jad Idriss Daniel J. Gromer Diane Saint-Victor Christiane S. Eberhardt Nadine Rouphael Suha Kalash

Hepatitis B virus (HBV) infection remains a major driver of liver-related morbidity and mortality among people living with HIV (PLWH), yet vaccine-induced protection is frequently suboptimal. HIV-associated immune dysfunction, including CD4+ T-cell depletion, altered antigen presentation, impaired T follicular helper cell support, and B-cell dysregulation, reduces seroprotection after standard recombinant HBV vaccines and may limit durability of antibody responses. Vaccine response is further influenced by HIV viral suppression, age, comorbidities, prior vaccine history, and baseline HBV serologic status, including isolated hepatitis B core antibody (anti-HBc) and occult HBV infection (OBI) considerations. Although antiretroviral therapy (ART) improves vaccine responsiveness, many PLWH fail to achieve protective hepatitis B surface antibody (anti-HBs) titers (≥10 mIU/mL) after conventional schedules, or experience antibody waning over time. Current guidelines recommend HBV vaccination for all susceptible PLWH with post-vaccination serologic testing and revaccination for nonresponders. Persistent implementation barriers, including incomplete series, vaccine hesitancy, stigma, and logistical constraints, continue to limit real-world impact. Emerging clinical trial data support CpG-adjuvanted HBV vaccines (HepB-CpG/Heplisav-B) and intensified dosing and schedules (double-dose or four-dose regimens) to improve seroprotection and generate higher peak anti-HBs titers, which may enhance durability. This review synthesizes guideline recommendations, immunologic mechanisms of hyporesponsiveness, predictors of vaccine response, and practical strategies to optimize HBV vaccination in PLWH.

Vaccines doi: 10.3390/vaccines14070622

Authors: Francesco De Maria Francesco Branda Giancarlo Ceccarelli Fabio Scarpa Massimo Ciccozzi Alessandro Russo

Background: Vaccine hesitancy has traditionally been understood as a multifactorial phenomenon shaped by individual beliefs, risk perceptions, and access barriers. However, the COVID-19 pandemic has fundamentally transformed the relationship between citizens, science, and public institutions, raising the question of whether vaccine hesitancy has evolved into a broader form of institutional distrust. Objective: This narrative review synthesizes evidence on vaccine confidence, trust dynamics, misinformation, and post-pandemic attitudes to propose a new conceptual framework, i.e., institutional hesitancy, that reframes vaccine acceptance within the wider context of institutional credibility, transparency, and legitimacy. Methods: We conducted a narrative synthesis of peer-reviewed literature, surveillance reports, and cross-national surveys published between 2015 and 2026, focusing on trust in science, governments, public health agencies, healthcare systems, and regulatory authorities as determinants of vaccination behavior. Results: The evidence consistently demonstrates that institutional trust is among the strongest predictors of vaccine acceptance, often surpassing traditional demographic and knowledge-based variables. The pandemic exposed and amplified pre-existing fractures in the relationship between citizens and institutions, creating a legacy of institutional skepticism that extends beyond COVID-19 vaccines to routine immunization programs, seasonal vaccination campaigns, and future pandemic preparedness. Traditional information-based approaches, which assume that knowledge deficits drive hesitancy, have proven insufficient when trust is compromised. Instead, rebuilding vaccine confidence requires sustained investment in institutional transparency, community engagement, and accountable governance. Conclusions: The post-pandemic era calls for a fundamental reconceptualization of vaccine hesitancy. We propose the institutional hesitancy framework as a complementary lens that shifts the analytical focus from individual knowledge deficits to relational dynamics between citizens and institutions. Addressing this challenge requires moving beyond communication campaigns toward long-term strategies that restore institutional trust and strengthen the resilience of public health systems.

Vaccines doi: 10.3390/vaccines14070621

Authors: Hongcen Yao Hongmei Lu Qi Zhu Jinhua Shen Xiaoya Fu Yihan Lu

Background: Human papillomavirus (HPV) vaccine has been proven a safe, necessary, and effective measure against HPV infection. However, HPV vaccine uptake remains limited among university students in China. This study investigated HPV vaccine intent among university freshmen in the largest university town in China. Methods: A cross-sectional online survey was conducted among unvaccinated female and male freshmen attending seven universities in Songjiang University Town, Shanghai, during 2024–2025. The questionnaire collected sociodemographic characteristics, HPV and HPV-vaccine-related knowledge, awareness, and vaccine intent. Factors associated with HPV vaccine intent were determined. Results: A total of 3397 valid questionnaires were collected, including female (60.02%) and male (39.98%) university freshmen. Overall, 76.12% were aware of HPV, 80.98% were aware of the HPV vaccine, and 84.31% expressed vaccine intent, with significantly higher rates among females than males (each p < 0.001). Socioeconomics, knowledge, awareness, sexual behavior, and HPV testing history were significantly associated with vaccine intent (each p < 0.05). The most common reason for no intent was perceived low risk of HPV-related diseases (40.53%). The most expected improvement measures were regulatory confirmation of vaccine safety and effectiveness (37.71%) and healthcare professionals’ recommendations (37.71%), with no gender difference (each p > 0.05). Notably, 4.00% refused HPV vaccination, regardless of improvement measures. Additionally, most respondents preferred financial supporting policies, regardless of gender or vaccine intent (each p > 0.05). Conclusions: University freshmen showed the disparity between high awareness/intent and low knowledge. Financial considerations may influence HPV vaccination decisions. Thus, improving knowledge, particularly among males, and providing financial support may enhance HPV vaccine intent.

Vaccines doi: 10.3390/vaccines14070620

Authors: MD Faizul Hussain Khan Tahsina Islam Abhishek Mishra Amine A. Kamen

Messenger RNA-lipid nanoparticle (mRNA-LNP)-based drug products represent a promising platform for prophylactic and therapeutic applications. However, their limited stability poses significant challenges for storage and global distribution. The instability of mRNA-LNP products makes them dependent on ultra-cold chain systems. This instability is driven by various physicochemical factors, including temperature, pH, light exposure, oxidation, aggregation, shear stress, and humidity. These factors destabilize the physical and chemical integrity of both mRNA and lipid nanoparticle (LNP) components, leading to reduced vaccine potency and potentially increasing the risk of adverse safety outcomes. Understanding these factors and their mechanisms is crucial for retaining mRNA-LNP efficacy. This review discusses the key physicochemical instability factors and molecular degradation mechanisms responsible for the structural and functional deterioration of mRNA-LNP formulations. Further, we summarize the stabilization strategies and analytical methods used to detect and quantify the degradation of mRNA-LNP products. Addressing these challenges is critical for advancing next-generation nucleic acid-based drug products and LNP-based delivery systems.

Vaccines doi: 10.3390/vaccines14070619

Authors: Michael Har-Noy

Background: Generating personalized anti-tumor immune responses remains a primary objective of precision oncology, yet conventional autologous platforms face critical biological and logistical constraints. While current research modifies allogeneic lines to evade host clearance, this perspective outlines a translational framework designed to leverage host-donor incompatibility as an active immunomodulatory asset to remodel the solid tumor microenvironment (TME). The framework proposes expanding a systemic pool of circulating, allo-specific host type 1 helper (Th1) memory cells via iterative intradermal injections of completely mismatched, activated donor Th1 cells, followed by a systemic intravenous rechallenge to provoke a controlled host-versus-graft (HvG) rejection response. Rapid intravascular clearance of donor cells is hypothesized to drive a transient, Type 1 cytokine wave that activates host effector populations via bystander pathways, promoting their extravasation into the tumor stroma to induce immunogenic cell death (ICD). This paradigm is contextualized by Phase 2B data in refractory microsatellite stable (MSS) metastatic colorectal cancer, where a dual-route allogeneic Th1 regimen demonstrated a median overall survival (OS) signal of 16.4 months despite an 89.5% conventional radiological progression rate. Ultimately, this framework provides a predictable, non-engineered conceptual mechanism to elicit a patient-specific adaptive immune response without ex vivo customization.

Vaccines doi: 10.3390/vaccines14070618

Authors: Christopher Michael Dyer Judith Welker Kholoud Assaad Nina Knab Sanjida Rahman Mim Maria Karathana Anne Kühn Sandra Kronmüller Peter Tinnemann Rebecca Zöllner

Background: Vaccinations are highly effective in preventing infectious diseases, which otherwise present a serious challenge to the health of individuals and public health. To identify potential gaps in vaccination coverage, we examined childhood vaccination levels in Frankfurt am Main (FFM) and the Rhein Neckar district (including Heidelberg city, RNHD) prior to, during and following the COVID-19 pandemic. Moreover, we explored various factors that appear to contribute to lower vaccination levels in specific communities in either or both locations. The results are intended to guide strategies for designing and improving vaccination services for specific groups in local health settings. Methods: A retrospective analysis was conducted to examine the vaccination rates of children in Frankfurt am Main and the Rhein Neckar district (including Heidelberg city) by using anonymized data from school entry examinations spanning the years 2017 to 2024. Data pre-processing, analysis, and visualization were performed using R (5.4.2). Frequencies and percentages were calculated for sociodemographic and vaccination rates (the completeness of the vaccination schedule recommended by STIKO for children). Multivariate logistic regression was performed to determine factors with a significant impact on vaccination uptake. Results: Multinomial logistic regression with ‘measles-only’ (Measles) as the reference category revealed distinct predictor patterns across vaccination levels. In both regions, children who completed preventive medical check-ups had higher odds of completing the schedule of vaccination plus at least one additional vaccine (ScheduledPlus) versus, measles-only vaccination. In RNHD, children from Eastern European language families and low- and medium-social-status backgrounds showed higher odds of completing the scheduled vaccinations without the recently introduced rotavirus vaccination (ScheduledNotRota), versus measles-only vaccination. In FFM, strong interaction effects were observed between medical examination completion and migration background, with children from non-German birthplaces showing dramatically reduced odds of complete vaccination when preventive care was incomplete. Discussion: The proportion of children with a complete vaccination status remained stable over the study period in both locations, with no evidence of post-pandemic decline. Nevertheless, this stability masks important heterogeneity in vaccine coverage patterns across sociodemographic groups. Systematic identification and modeling of interactions between nationality, parental employment, and healthcare utilization tell a compelling “double jeopardy” story that the effects of these risk factors are not additive but synergistic. Regular medical check-ups remain an important factor in ensuring high vaccination coverage among children until they start school and underscore the justification for such established preventive care programs. A nuanced understanding, however, is crucial for moving beyond simplistic, one-size-fits-all public health messaging.

Vaccines doi: 10.3390/vaccines14070617

Authors: Yang Cao Hao Wang Ziwei Zhao Zhen Li Hai Fang

Objectives: To investigate associations between varicella vaccination and self-reported contact history with varicella or herpes zoster among clinically diagnosed varicella cases in Chaoyang District, Beijing, China. Methods: A retrospective observational study was conducted among 4441 clinically diagnosed varicella cases reported from 2017 to 2025. Multivariable logistic regression examined associations between vaccination status, number of doses, time since vaccination, and reported contact history with varicella and/or herpes zoster, adjusting for age, sex, and year of diagnosis. Results: Vaccinated cases had significantly higher odds of reporting contact with varicella or zoster compared with unvaccinated cases (OR = 1.34, 95% CI: 1.14–1.58). Both 1-dose and 2-dose recipients showed similar associations. A gradient of increasing odds was observed with longer time since vaccination, reaching OR = 3.17 (95% CI: 1.39–7.22) for 10 or more years since last dose. Associations were primarily driven by reported varicella contact rather than herpes zoster contact. Sensitivity analysis confirmed robustness of findings. Conclusions: Varicella vaccination was positively associated with reporting an identifiable exposure source. Vaccination status may influence completeness of exposure ascertainment in varicella surveillance and should be considered when interpreting contact tracing data.

Vaccines doi: 10.3390/vaccines14070616

Authors: Özge Kilinç Ufuk Ünlü

Background: In Turkey, meningococcal, rotavirus, and HPV vaccines are not included in the national schedule. We aimed to assess whether a face-to-face educational intervention could improve physicians’ knowledge about these vaccines and influence their subsequent counseling and recommendation practices. Methods: We used a two-phase intervention with pre/post assessment and a 4–6-week follow-up among family physicians. In Phase 1, participants received an in-person structured educational intervention on meningococcal, rotavirus, and HPV vaccines, and their knowledge was evaluated using identical true/false tests administered before and after the session. Phase 2, conducted 4–6 weeks later, measured changes in physicians’ self-reported frequency of providing recommendations about these vaccines, and whether they or their first-degree relatives had received any of the vaccines after the structured educational intervention. Differences in paired proportions were analyzed using McNemar’s test (p < 0.05). Results: Ninety-one physicians completed Phase-1; 70 from the same cohort completed Phase-2. Following the educational intervention, correct responses increased across multiple items: e.g., “Rotavirus vaccine is live” 89.0%→100% (p = 0.002); “Only humans are reservoir for meningococcal infection” 50.6%→96.7% (p < 0.001); “Meningococcal vaccine cannot be co-administered” (false) 70.3%→96.7% (p < 0.001). Phase-2 showed more proactive practice: for HPV, 52.9% reported recommending it “upon family request” and 27.1% “at every visit”; for rotavirus, these were 37.1% and 35.7%, respectively. Overall, 52.9% reported having administered one of the three vaccines to themselves or first-degree relatives after structured educational intervention; 62.2% rated the educational intervention’s influence on that decision as 10/10. Conclusions: A structured educational intervention improved family physicians’ knowledge and was associated with more proactive vaccine counseling and recommendation practices.

Vaccines doi: 10.3390/vaccines14070615

Authors: Yanping Qiu Yan Zhang Shuangshuang He Yutian Wang Ruixin Wang Yanxiao Han Wen He Eiketus Sho Shaohua Han Haojie Wu

Background/Objectives: Pandemic influenza remains a persistent global threat, and while vaccination is the primary preventive measure, conventional vaccines often induce narrow, strain-specific immunity. This study evaluated the immunogenicity, protective efficacy, and cross-protective potential of a CpG-adjuvanted trivalent inactivated influenza vaccine (CpG-TIV) administered intramuscularly at high and low doses in ferrets. Methods: Groups of influenza-seronegative ferrets received two intramuscular injections, 3 weeks apart, of high- or low-dose CpG-TIV or a commercial non-adjuvanted trivalent vaccine. Three weeks after the second immunization (Day 42), serum was obtained, and the ferrets were subsequently challenged intranasally with homologous H1N1 and influenza B viruses, as well as a heterologous drifted H3N2 strain. Clinical signs, body weight, nasal viral load, and lung histopathology were monitored following the viral challenge. Results: CpG-TIV induced significantly higher dose-dependent HI and IgG antibodies than the commercial unadjuvanted vaccine. High-dose CpG-TIV markedly reduced weight loss, clinical symptoms, nasal viral load (by up to 99%), and lung pathological damage. Notably, high-dose CpG-TIV provided significant cross-protection against heterologous H3N2, whereas the commercial vaccine showed no protective effect. At Day 42, HI GMTs in the high-dose group reached 500, 254, and 594 against H1N1, H3N2, and B strains, respectively, with a maximal 2.58 log10 reduction in H1N1 viral load. Conclusions: High-dose CpG-TIV demonstrates strong immunogenicity and robust dose-dependent homologous and heterologous cross-protection in ferrets. The combination of a CpG adjuvant and high-dose antigen broadens protection against drifted influenza viruses, overcoming the narrow coverage of conventional vaccines. These data support further clinical development of this broad-spectrum influenza vaccine candidate.

Vaccines doi: 10.3390/vaccines14070614

Authors: Na Zuo Xin Zheng Rameez Ishaq Deshan Ren Ao Hu

Human viral entry receptor mouse models exist to overcome a fundamental experimental barrier: many clinically important viruses bind their human entry factors far more efficiently than the corresponding murine orthologs, leaving conventional mice unable to support authentic infection, physiological tissue tropism, or meaningful countermeasure evaluation. This review is organized around the receptor-humanization concept rather than around a single coronavirus model. Engineering strategies compared here include random transgenesis, endogenous-locus knock-in, minimal receptor-interface humanization, conditional and inducible expression, and transient vector-mediated delivery. Receptor systems covered span human angiotensin-converting enzyme 2 (hACE2)-dependent sarbecoviruses, human dipeptidyl peptidase 4 (hDPP4)-dependent Middle East respiratory syndrome coronavirus (MERS-CoV), human cluster of differentiation 4/human C-C chemokine receptor type 5 (hCD4/hCCR5)-dependentt human immunodeficiency virus type 1 (HIV-1), adenovirus receptor models, human intercellular adhesion molecule 1 (hICAM-1) rhinovirus systems, hepatitis C virus (HCV), hepatitis B virus (HBV), and hepatitis D virus (HDV) entry-factor models, measles receptor models, poliovirus receptor/CD155 (PVR/CD155) models, human scavenger receptor class B member 2 (hSCARB2) enterovirus systems, and human transferrin receptor 1 (hTfR1) arenavirus models. We then discuss how these platforms support antibody evaluation, Fc-effector analysis, vaccine protection, variant benchmarking, and safety assessment. These models yield the most reliable data when the experimental question is explicitly entry-dependent and when receptor expression level, anatomical distribution, pathology window, and immune context have all been independently validated. They are least informative when receptor expression is non-physiological, when disease readouts are driven by promoter artifacts, or when post-entry species barriers remain the dominant bottleneck. A validation-centered framework is therefore proposed to guide the selection of each model for the specific antiviral antibody or vaccine question it can legitimately answer.

Vaccines doi: 10.3390/vaccines14070613

Authors: Fakry F. Mohamed Hassanein H. Abozeid Matt Murray Adel M. Talaat

Background: Nucleic acid vaccines adjuvanted with lipid nanoparticles (LNPs) are a simple and effective means of protection against infectious diseases through the delivery of antigen(s) that elicit(s) specific immunity. DNA vaccines are not commercially available for poultry mainly due to low protective efficacy and the associated production cost. Methods: We introduced here a novel nanoadjuvant system (namely, QTAP) comprising DOTAP and Quil-A for efficient delivery of plasmid DNA (pDNA) constructs into cells and boosting immune responses of chickens. Variable QTAP-pDNA-LNPs formulas were investigated for their physicochemical characteristics, cellular transfection, and in vivo efficacy in a vaccine/challenge model using pDNA encoding both S and N proteins of avian Infectious Bronchitis Virus (IBV). Results: Under electron microscopy, all LNP formulas were spherical in shape and had an overall size range of 45.4–376.3 nm. The formula with the smallest size had the lowest pDNA encapsulation and the highest polydispersity index (PDI). On the contrary, formulas with larger sizes and lower PDI values encapsulated a higher concentration of plasmid payload. Interestingly, the high-payload vaccine formula was stable at both 25 °C and 4 °C for up to 6 weeks of storage, but its gene expression dropped beyond this point at both temperatures. Following immunization of chickens, all groups were challenged with a virulent IBV. Surprisingly, both formulas were able to reduce the IBV viral shedding, indicating their effectiveness even when low concentrations of pDNA were incorporated in LNPs. However, pre-challenge sera from immunized chicks did not elicit IBV-specific antibodies, compared to birds immunized with a commercial live-attenuated IBV vaccine. Conclusions: This study suggests that the QTAP nanoadjuvant system is a safe and effective adjuvant for DNA immunization in poultry that could also be further developed for commercialization.

Vaccines doi: 10.3390/vaccines14070612

Authors: David Valentin Mangaloiu Dag S. Halvorsen Alexandra Denisa Raris Aramă Sorin Ștefan Victoria Aramă Florentina Ligia Furtunescu

Background/Objectives: Measles remains a significant public health concern in Romania, with recurrent ongoing nationwide outbreaks despite the availability of the measles–mumps–rubella (MMR) vaccine. This study investigates the epidemiological, clinical, and sociocultural dimensions of measles among Romanian adults, with a particular focus on a vulnerable group, the Roma population. Methods: We conducted a retrospective cohort study using clinical data from a tertiary hospital in Bucharest, Romania. The study included adult patients hospitalized with measles between July 2023 and April 2024. In a subsequent phase, we carried out a cross-sectional survey among hospitalized measles patients to assess their perception and understanding of measles and the MMR vaccine, with particular attention to responses from Roma participants. Results: A retrospective investigation of 100 hospitalized adult patients with laboratory-confirmed diagnoses of measles demonstrated frequent complications such as hepatic involvement (85/100), pneumonia (68/100), and respiratory failure (21/100). Only 6/100 of patients were fully vaccinated. Rhabdomyolysis was significantly more common in unvaccinated individuals and women. No deaths were recorded, and no ICU admissions occurred. Among the hospitalized patients, 49 adults responded to a vaccine centered questionnaire. We report a notable vaccine hesitancy, particularly among the Roma respondents. Socioeconomic factors such as low income, limited education, and lack of health insurance were significantly associated with negative perceptions of the MMR vaccine. A statistically significant association was observed between Roma ethnicity and the belief that the MMR vaccine causes autism. Conclusions: These findings highlight the urgent need for targeted public health interventions with culturally adapted education campaigns to improve vaccination coverage and thereby protect vulnerable adult populations in Romania.

Vaccines doi: 10.3390/vaccines14070611

Authors: Carmine Siniscalchi Egidio Imbalzano Manuela Basaglia Nicoletta Cerundolo Tiziana Meschi Beatrice Prati Alberto Parise Antonio Nouvenne Pierpaolo Di Micco

Six years after the emergence of SARS-CoV-2, COVID-19 remains a dynamic public health challenge shaped by viral evolution, heterogeneous population immunity, changing vaccine strategies, and the long-term consequences of acute infection. Although the transition from pandemic emergency to endemic circulation has reduced the global burden of severe disease, COVID-19 continues to affect vulnerable populations, particularly older adults, frail patients, immunocompromised individuals, and subjects with multiple comorbidities. Vaccination has substantially modified the clinical course of infection, reducing hospitalization, intensive care admission, and mortality, while also reshaping surveillance priorities toward variant monitoring, vaccine effectiveness, waning immunity, breakthrough infections, and long COVID. At the same time, the pandemic has highlighted the need for integrated clinical risk stratification, including age, sex, frailty, inflammatory biomarkers, respiratory support requirements, and thromboembolic risk. Venous and arterial thrombotic complications have represented a key feature of severe COVID-19 and remain relevant for both acute management and post-discharge follow-up. This narrative review summarizes the main lessons learned from six years of COVID-19, focusing on epidemiology, vaccination campaigns, clinical risk assessment, thromboembolic complications, and surveillance strategies. Particular attention is given to the need for multidisciplinary and data-driven approaches capable of integrating virological, epidemiological, clinical, geriatric, and vascular medicine perspectives. Future COVID-19 surveillance should move beyond case counting and incorporate vaccine impact, population vulnerability, thrombotic and bleeding complications, long-term outcomes, and preparedness for emerging variants.

Vaccines doi: 10.3390/vaccines14070610

Authors: Min Xie Shan Lai Jing Lei Qin Feng Qiong Liang Miao Zhao

Background and Objectives: HPV vaccination is critical for cervical cancer prevention, but HPV vaccination coverage stays low among young women in China. While various factors shaping vaccination willingness have been explored, the role of personality traits remains insufficiently understood. This study investigated the relationships between Big Five personality traits and three facets of HPV vaccination willingness (consideration, determination, recommendation) among female healthcare undergraduates. We also specifically examined whether academic major moderated the association between extraversion and vaccination willingness. Methods: A cross-sectional survey was conducted among 703 female undergraduates enrolled in healthcare majors at a medical college in Chengdu using a stratified cluster sampling method. Data were collected via online questionnaires, including the 10-item Big Five Inventory (BFI-10) and a scale measuring three motivational facets of HPV vaccination willingness: consideration, determination and recommendation. Descriptive statistics, correlation analysis and hierarchical regression analysis were performed to examine the research questions. Results: A total of 672 valid questionnaires were analyzed. Distinct associations were found between personality dimensions and each facet of vaccination willingness. Agreeableness (β = 0.193, p < 0.01) and openness (β = 0.079, p < 0.05) correlated with vaccination consideration (ΔR2 = 0.061). Extraversion (β = 0.103, p < 0.05), agreeableness (β = 0.113, p < 0.01) and conscientiousness (β = 0.096, p < 0.05) correlated with determination (ΔR2 = 0.049). Extraversion (β = 0.125, p < 0.01), agreeableness (β = 0.129, p < 0.01), conscientiousness (β = 0.102, p < 0.01) and neuroticism (β = 0.081, p < 0.05) were positively related to recommendation willingness (ΔR2 = 0.061). Academic major did not exert a significant moderating effect. Conclusions: The findings highlight the complexity of the relationships between personality traits and vaccination attitudes and behaviors. While the observed associations were modest in magnitude, this study provides preliminary empirical evidence that may inform personality-sensitive HPV vaccination promotion strategies. Tailored, multi-dimensional interventions that consider diverse population characteristics could be considered to optimize HPV vaccination outreach, though their effectiveness awaits further validation.

Vaccines doi: 10.3390/vaccines14070609

Authors: Yeonji Kim Sun A. Choi Wonjun Kim Yongwoo Shin Sua Choi Ji-yun Sung So-Jeong Kim Seong Cheol Moon Su Jin Lee Xinghua Zheng Se Young Lee Keun Seung Ahn Dongseob Tark Jung Hyang Sur Weonhwa Jheong

Background/Objective: African swine fever (ASF), caused by African swine fever virus (ASFV), is a highly contagious viral disease affecting domestic pigs and wild boars, causing severe economic losses. Although commercial ASF vaccines have recently been approved in Vietnam, controlling ASF transmission remains challenging. Since injection-based vaccination is impractical for wild boars, oral vaccination is considered essential. This study aimed to evaluate the safety, immunogenicity, protective efficacy, and dose-related outcomes of ASFV-G-ΔI177L/ΔLVR, a live attenuated ASFV vaccine candidate with deletion in the I177L gene and left variable region (LVR), administered orally to convention pigs. Methods: The ASFV-G-ΔI177L/ΔLVR vaccine candidate was orally administered to conventional pigs at three dose levels (102.25, 105.0, and 106.0 TCID50/dose). At 28 days post-vaccination, pigs were challenged intramuscularly with a virulent ASFV field strain at 102.0 HAD50/mL and monitored clinically. Protection was assessed by ASFV-specific antibody responses (p32) and survival following challenge. Results: Oral immunization was well tolerated, with no vaccine-associated clinical signs observed before challenge. Following challenge, vaccinated pigs showed different protective outcomes among the tested dose groups, with survival rates of 1/4 (102.25 TCID50/dose), 4/4 (105.0 TCID50/dose), and 3/4 (106.0 TCID50/dose), respectively. Pigs that succumbed to infection showed neither detectable viremia nor ASFV-specific antibodies before challenge, suggesting incomplete vaccine uptake may have resulted in insufficient immune induction rather than an adverse effect associated with vaccination. In contrast, pigs that seroconverted prior to challenge were fully protected and exhibited lower viral loads than the control animals. Conclusions: ASFV-G-ΔI177L/ΔLVR was well tolerated as an oral live attenuated vaccine candidate and induced protective immunity against virulent ASFV challenge under the present experimental conditions. Notably, complete protection was observed in the 105.0 TCID50/dose group, supporting the potential of this vaccine candidate for oral immunization strategies against ASF. However, the present data do not allow a definitive conclusion regarding the dose–response relationship, and further studies with larger group sizes and field-relevant models are needed to refine dose selection and practical applicability, particularly for wild boar vaccination.

Vaccines doi: 10.3390/vaccines14070608

Authors: Jeanine P. D. Guidry Linnea I. Laestadius Yil Engbersen-Severijns Carrie A. Miller Michael P. Stevens Candace W. Burton Kellie E. Carlyle Janina-Marie Huss Kathryn Moffett Paul B. Perrin

Background: West Virginia is of particular concern regarding HPV vaccine hesitancy, currently ranking 45th among U.S. states in HPV vaccine uptake. General vaccine hesitancy and HPV- and HPV vaccine-specific misinformation, both associated with lower vaccination, have increased in recent years, complicating efforts to identify key drivers of HPV vaccine acceptance and effective intervention targets. Methods: This study used a Qualtrics survey of n = 330 parents of children aged 0–14 in West Virginia. Measures included parental HPV vaccine acceptance for their youngest child (reflecting either completed vaccination or intention to vaccinate), general vaccine hesitancy measured using the Vaccine Hesitancy Scale (VHS), and endorsement of nine common HPV- and HPV vaccine-specific misinformation statements. Misinformation items were summed and demonstrated good internal reliability (Cronbach’s α = 0.868). Results: Hierarchical logistic regression analyses indicated significant racial/ethnic differences across all model steps, with non-White parents less likely to report HPV vaccine acceptance for their child (p < 0.001). In Step 2, lower levels of general vaccine hesitancy predicted higher HPV vaccine acceptance (p < 0.001). In the final model, higher endorsement of HPV- and HPV vaccine-specific misinformation was associated with lower HPV vaccine acceptance (p = 0.035). Conclusions: These findings underscore the independent and additive influence of general vaccine hesitancy and HPV- and HPV vaccine-specific misinformation on parental HPV vaccine acceptance in West Virginia. Community-engaged public health strategies should prioritize strengthening vaccine confidence and directly addressing HPV- and HPV vaccine-specific misinformation, particularly among underserved populations.

Vaccines doi: 10.3390/vaccines14070607

Authors: Siqi Guo

Nanosecond electric pulses (nsEPs) are an emerging pulsed-power technology with unique bioelectric characteristics distinct from conventional long-pulse electroporation. As a tunable physical modality, nsEPs can modulate intracellular structures, membrane dynamics, and signaling pathways. Increasing evidence supports nsEPs as a promising non-thermal tumor ablation approach due to their high spatial precision, preservation of critical tissue structures, and minimal adverse effects. One of the most significant discoveries associated with nsEP tumor ablation is the induction of potent systemic antitumor immunity, particularly in situ vaccination (ISV) effects and, in some cases, abscopal effects against distant untreated tumors. Substantial evidence demonstrates that nsEPs can function as authentic immunogenic cell death (ICD) inducers by promoting the release of damage-associated molecular patterns (DAMPs), including calreticulin (CRT), ATP, and HMGB1. These events facilitate dendritic cell activation, antigen presentation, and the generation of long-term antitumor T-cell immunity. In addition to enhancing tumor immunogenicity, nsEPs profoundly remodel the tumor microenvironment (TME), including disruption of tumor vasculature, reduction in immunosuppressive cell populations, and alteration of stromal components. Emerging studies further suggest that nsEPs act as electric metabolic modulators capable of influencing mitochondrial function, calcium signaling, and metabolism-associated signaling pathways. Current evidence indicates that the immunological outcomes induced by nsEPs are highly dependent on pulse parameters, waveform characteristics, and tumor type. Despite its considerable therapeutic promise, the development of nsEP-induced ISV immunotherapy faces several important challenges, including standardization and optimization of pulse protocols, identification of critical molecular and cellular targets, and clarification of tumor- and cell-type-specific responses. Addressing these challenges through multidisciplinary collaboration and advanced technologies, including multi-omics, spatial analysis, and computational modeling, may accelerate the development of next-generation bioelectric immunotherapies for cancer treatment.

Vaccines doi: 10.3390/vaccines14070606

Authors: Nelly Otte Amir Maleki Kahaki Gerda Wurpts Thomas Kraus Julia Krabbe

Background: Yellow fever vaccination is recommended for travelers visiting endemic regions in South America and Africa. The live-attenuated vaccine (Stamaril®, Sanofi Pasteur) is produced in embryonated chicken eggs and contains residual ovalbumin, posing a challenge for individuals with egg protein allergy. Case Presentation: We report the case of a 35-year-old male disaster relief worker with confirmed egg protein allergy and moderate sensitization but no history of anaphylaxis. Under normal circumstances, a statement confirming that vaccination is not possible would be sufficient for entry. However, due to his work-related duties and the relevant guidelines from his employer, there was an urgent need for vaccination despite his egg protein allergy. A comprehensive allergy work-up including skin prick testing, serum-specific IgE, and oral provocation testing revealed a moderate allergy without systemic reactions. Intervention: Following informed consent and risk assessment, a fractional dose (0.1 mL) of the reconstituted yellow fever vaccine was administered under close monitoring. The patient developed a localized dermal reaction without systemic symptoms. Post-vaccination neutralization testing confirmed seroconversion indicating protective immunity. Discussion: Although yellow fever vaccination is considered contraindicated in individuals with severe egg protein allergy, the literature supports its cautious use in selected cases. Fractional dosing has emerged as an effective dose-sparing strategy. Studies show that even in egg protein-allergic individuals, adverse events are rare. Conclusions: In this case, a fractional yellow fever vaccination was safe and an effective option for an egg-allergic individual in a high-risk occupational setting, supporting a personalized approach based on clinical risk assessment and current evidence.

Vaccines doi: 10.3390/vaccines14070605

Authors: Jun Li Xinyang Li Kaichao Yang Yuxia Yun Yanyan Yang Lijun Deng Zunshui Li Xiaoyang Wang Xiaoxiao Zhang Lubin Shi Binghui Du Yanfang Ji Yonghao Guo Yanyang Zhang Shuaiyin Chen

Objectives: To identify factors influencing influenza vaccination willingness and uptake among adults aged ≥60 years in Henan Province and to evaluate the effect of a brief educational intervention on vaccination willingness and behavior. Methods: In September 2024, a cross-sectional survey based on the Behavioral and Social Drivers (BeSD) framework was conducted among adults aged ≥60 years across five counties in Henan. For participants without baseline willingness, a 3 min one-on-one educational intervention was delivered. In May 2025, following the end of the 2024–2025 influenza vaccination season (which runs from 1 October to 31 March in Henan Province), we retrieved vaccination records for all participants from the Henan Provincial Immunization Information System. This system captures all influenza vaccinations administered at designated vaccination clinics across the province. To ensure completeness for doses administered outside the provincial system (e.g., in other provinces or at private healthcare facilities), we conducted telephone follow-up interviews with all participants whose baseline vaccination intention was inconsistent with their actual vaccination behavior (i.e., willing but unvaccinated or unwilling but vaccinated). During these interviews, for those who reported receiving the vaccine outside Henan Province or at private facilities, we inquired about the specific date and location of vaccination to supplement the registry data. We also explored the reasons behind the intention–behavior discrepancy. For these participants, we requested vaccination certificates or other supporting documentation to confirm their vaccination status. Results: Baseline vaccination willingness was 68.20% (1630/2390), whereas the actual vaccination rate was only 6.95% (166/2390), yielding a willingness-to-behavior conversion rate of 9.51% (155/1630) among those with baseline willingness. Of the 760 participants without baseline willingness, 543 (71.45%) completed the 3 min one-on-one instant educational intervention and the follow-up assessment; the remaining 217 were excluded due to refusal or loss to follow-up. Among these 543 completers, 46 (8.47%) became willing to vaccinate, and eight (1.47%) were subsequently vaccinated. Multivariate analysis identified the social processes dimension as the strongest correlate of both willingness (OR = 1.38 per 1-point increase, 95% CI: 1.33–1.44) and uptake (OR = 1.12, 95% CI: 1.03–1.22). Urban residence was associated with higher willingness (OR = 1.41, 95% CI: 1.12–1.78) and higher uptake (OR = 1.64, 95% CI: 1.11–2.42). Current smokers had a significantly lower uptake than never smokers (OR = 0.43, 95% CI: 0.22–0.85). Among the 11 participants without baseline willingness who were eventually vaccinated (eight from the intervention group and three from the non-intervention group), family/friend influence (63.64%, 7/11) and physician recommendation (36.36%, 4/11) were the primary drivers. For those with willingness but no action (n = 1475), the main barriers were perceived good health (33.29%), high vaccine cost (27.12%), and lack of time (26.31%). Conclusions: Influenza vaccination among older adults in Henan exhibits a “high willingness, low conversion” pattern, with social processes as the strongest driver bridging the intention–behavior gap. A brief educational intervention improved willingness but failed to translate into meaningful uptake, underscoring that knowledge transfer alone is insufficient. We recommend a multi-component strategy that (1) mobilizes family members and community doctors as trusted vaccine advocates; (2) leverages family and village doctor networks to reduce urban–rural disparities; (3) counters the “perceived good health” barrier with age-specific risk communication; and (4) integrates vaccine recommendations into routine care for high-risk groups, particularly frequent outpatient attendees and smokers.

Vaccines doi: 10.3390/vaccines14070604

Authors: Lingling Yao Zoltán Megyesi Paul V. Lehmann Greg A. Kirchenbaum

Background: Despite the circulation of evolutionarily related cold-causing coronaviruses (CCCs) in the pre-COVID era, most individuals lacked pre-existing serum IgG and/or class-switched memory B cell (Bmem) reactivity for the SARS-CoV-2 Spike (S) glycoprotein expressed by the ancestral Wuhan-Hu-1 (WH1) strain. Subsequent priming of the immune system through natural infection or prophylactic COVID-19 mRNA vaccination successfully generated robust Bmem responses against the WH1-S antigen, along with eliciting cross-reactivity for the future Omicron (BA.1) variant responsible for breakthrough infections (BTIs). However, to what extent immunological imprinting of Bmem towards the WH1-S antigen detrimentally constrains the elicitation of variant-specific antibody responses following subsequent booster vaccinations or BTIs—a phenomena referred to as “original antigenic sin”—remains an unresolved and open question. Methods: Using ImmunoSpot®, we evaluated peripheral blood mononuclear cells (PBMCs) from defined human cohorts for IgG+ ASC reactivity against Spike proteins representing CCCs and SARS-CoV-2. Additionally, we developed a novel dual-label inverted FluoroSpot assay to distinguish between strain-specific and cross-reactive IgG+ ASCs recognizing epitopes in the receptor binding domain (RBD) of SARS-CoV-2 Omicron variants. Results: Our data demonstrate a lack of appreciable back-boosting of IgG+ Bmem recognizing structurally conserved epitopes shared between CCCs and SARS-CoV-2. Moreover, we found evidence for immunological imprinting and the preferential expansion of Bmem recognizing cross-reactive epitopes in the RBD following BTI. Nevertheless, Omicron strain-specific Bmem were detected in PBMC donors collected in 2025. Conclusions: Our novel inverted dual-label FluoroSpot methodology evidenced preferential expansion of cross-reactive Bmem following breakthrough SARS-CoV-2 infection and supports the influence of original antigenic sin shaping the recall response. Moreover, the inverted dual-label assay provides a highly flexible and easily implementable technique for distinguishing between strain-specific and cross-reactive B cell responses and has broad applications in translational vaccine research against pathogens that undergo antigenic drift.