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Keywords = multi-dose vaccines

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16 pages, 577 KB  
Article
The Role of Adjuvant Nonavalent HPV Vaccination After LLETZ in Patients with Isolated CIN2: A Controlled Cohort Study
by Vincenzo Pinto, Miriam Dellino, Marco Cerbone, Edoardo Di Naro, Achiropita Lepera, Silvio Tafuri, Gerardo Cazzato and Ettore Cicinelli
Pathogens 2026, 15(8), 814; https://doi.org/10.3390/pathogens15080814 - 1 Aug 2026
Viewed by 236
Abstract
Background: Women treated for cervical intraepithelial neoplasia grade 2 (CIN2) face an increased risk of disease recurrence due to persistent or newly acquired human papillomavirus (HPV) infections, suggesting a potential role for adjuvant HPV vaccination. While a growing body of literature evaluates the [...] Read more.
Background: Women treated for cervical intraepithelial neoplasia grade 2 (CIN2) face an increased risk of disease recurrence due to persistent or newly acquired human papillomavirus (HPV) infections, suggesting a potential role for adjuvant HPV vaccination. While a growing body of literature evaluates the outcomes of HPV vaccination following a large loop excision of the transformation zone (LLETZ) for high-grade squamous intraepithelial lesions (CIN2–3), data specifically focused on isolated CIN2 remain limited. This study aims to evaluate the clinical efficacy of the nonavalent HPV vaccine (9vHPV) as an adjuvant strategy to reduce CIN2+ recurrence in women undergoing LLETZ for histologically confirmed, isolated CIN2. Methods: Between November 2017 and November 2024, women undergoing LLETZ for histologically confirmed CIN2 received their first dose of adjuvant 9vHPV within one month of surgery. Patients who achieved double-negative co-testing (Pap test and high-risk HPV DNA test) at the 6-month post-LLETZ follow-up were included in the study group. Conversely, patients with at least one positive test result at 6 months were excluded to rule out residual disease. The study group underwent a subsequent Pap smear at 12 months and a full co-test at 18 months post-surgery; upon achieving negative results through the 18th month, patients returned to the organized screening program. The primary outcome was the recurrence rate, defined as histologically confirmed CIN2+ occurring more than 6 months post-treatment. It was compared against an unvaccinated historical control group treated with LLETZ prior to the study period. The secondary outcome evaluated the prevalence of HPV genotypes at baseline and at the time of recurrence. Results: In the vaccinated group, 3 women (2.03%) experienced CIN2+ recurrence compared to 6 women (5.71%) in the unvaccinated control group. This represents an absolute risk difference of 3.69% and a relative risk reduction of 64.6%, though the difference did not reach statistical significance via Fisher’s exact test (p = 0.165). In the study group, two recurrences were detected at 18 months (associated cytologies: ASC-H and LSIL; genotypes: HPV 51/53 and 16, respectively) and one at four years (cytology: HSIL; genotype: HPV 33/58). In the control group, recurrences occurred at 12 months (n = 3), 18 months (n = 2), and four years (n = 1). Associated cytology revealed HSIL in three cases, ASC-H in one case, LSIL in one case, and ASCUS in the final case. The corresponding HPV genotypes were 16 (two cases), 18, 51, 31 and 56 (co-infection), and one case of high-risk HPV, not further genotyped. Conclusions: Adjuvant 9vHPV administration after LLETZ for isolated CIN2 was associated with a clinically substantial lower absolute recurrence rate (2.03% vs. 5.71%, corresponding to a 64.6% relative risk reduction). Although this reduction did not achieve statistical significance (p=0.165) due to our small sample size and a low baseline recurrence rate in this isolated cohort, the effect size is highly comparable to broader CIN2+ studies. The study was likely underpowered to prove statistical significance, and larger multi-center studies are required to confirm the statistical value of adjuvant vaccination specifically in isolated CIN2 lesions. Full article
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14 pages, 2528 KB  
Article
Pilot-Scale Downstream Processing of Recombinant Influenza Virus Vectors Expressing Brucella spp. Antigens Using an Integrated Membrane-Chromatography Purification Platform
by 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 and Nurlan Akmyrzayev
Vaccines 2026, 14(7), 626; https://doi.org/10.3390/vaccines14070626 - 17 Jul 2026
Viewed by 825
Abstract
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 [...] Read more.
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. Full article
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14 pages, 428 KB  
Article
Influenza Vaccination Willingness, Uptake, and Behavioral Drivers Among Adults Aged ≥60 Years in Henan Province: A BeSD-Based Survey with Registry Follow-Up
by 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 and Shuaiyin Chen
Vaccines 2026, 14(7), 605; https://doi.org/10.3390/vaccines14070605 - 9 Jul 2026
Viewed by 489
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue The Changing Epidemiology of Vaccine-Preventable Diseases)
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16 pages, 1114 KB  
Article
Pakistan’s 2025 HPV Vaccine Phase I Rollout: Community Response, Implementation Challenges & Way Forward
by Wei Xia, Soofia Yunus, Atta Ur Rehman, Shah Nawaz Jiskani, Muhammad Imran Qureshi, Shawana Farooq, Inam Bhatti, Sunday Audu, Syed Natiq Abbas Kazmi and Rozina Khalid
Vaccines 2026, 14(6), 537; https://doi.org/10.3390/vaccines14060537 - 17 Jun 2026
Viewed by 964
Abstract
Background: The International Agency for Research on Cancer estimated around 3197 annual deaths along with 5008 newly diagnosed cases of cervical cancer in Pakistan. Worldwide, introduced in 164 WHO member states, the HPV vaccine provides over ninety percent (90%) protection from human papillomavirus [...] Read more.
Background: The International Agency for Research on Cancer estimated around 3197 annual deaths along with 5008 newly diagnosed cases of cervical cancer in Pakistan. Worldwide, introduced in 164 WHO member states, the HPV vaccine provides over ninety percent (90%) protection from human papillomavirus (16 & 18 types) infections. This article intended to document the vaccine (HPV) introduction in a low-middle-income country through the lens of EPI preparedness, vaccination coverage achieved, community acceptance, and implementation challenges during Phase I. Methodology: The research applied a qualitative and quantitative mix method to review the intricate procedure of new vaccine rollout within the national context. A qualitative participant observation approach assessed the planning, approval, and implementation phases of the HPV vaccine. Quantitative data statistics were evaluated for national & regional vaccination coverages, rapid convenience assessment findings, and adverse events reports. Results: The overall reported administrative HPV campaign coverage was 75%, with the maximum regional coverage of 81% by the Punjab, followed by 66% of the Sindh, 43% by the Azad Jammu & Kashmir, and 38% by the Islamabad. Rapid Convenience Assessment findings highlighted the main reasons for refusal (71%), with unavailable girls during the campaign (22%) for non-HPV vaccination. Community acceptance varied across the regions, with notable challenges in implementation being observed. Discussion & Way Forward: Initial phase campaign coverage (70.6%) was greater than the worldwide reported first dose mean coverage (61.6%) for the same multi-age cohort, indicative of an encouraging start in resource limited setting. Documented coverage was below the high-performing countries but comparable to multiple low and middle-income countries. Federal Directorate of Immunization, in collaboration with provincial EPI stakeholders, should prioritize including the newly introduced HPV vaccine in the routine immunization schedule of the Phase I regions and should also implement the lessons learned in the subsequent rollout phases in 2026 in Khyber Pakhtunkhwa and 2027 in Balochistan & Gilgit Baltistan. Expanding fixed EPI sites for HPV vaccination, promoting school-centered vaccination, rationalizing outreach in marginalized areas, sustaining the cold chain system, implementing a culturally acceptable communication plan, and resolving internet connectivity challenges are the key strategies to address implementation challenges. Full article
(This article belongs to the Special Issue HPV Vaccination and Primary HPV Screening)
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19 pages, 2430 KB  
Article
Three Competitive ELISAs to Quantify the D-Antigen Content of Aluminum-Salt Adjuvanted Recombinant Polio VLPs (Types 1, 2, 3) to Enable Preformulation Characterization Studies
by Yanli Liu, John M. Hickey, Geetha Satya Sainaga Jyothi Vaskuri, Brandy Dotson, Sangeeta B. Joshi and David B. Volkin
Vaccines 2026, 14(6), 479; https://doi.org/10.3390/vaccines14060479 - 28 May 2026
Viewed by 692
Abstract
Background/Objectives: Recombinant poliovirus (PV) virus-like particle (VLP) antigens mimic the conformation of the surface proteins in native PVs (i.e., serotype-specific D-antigen epitopes). Since they lack genomes and are non-infectious, PV-VLPs offer the promise of a safer, next-generation polio vaccine compared to traditional inactivated [...] Read more.
Background/Objectives: Recombinant poliovirus (PV) virus-like particle (VLP) antigens mimic the conformation of the surface proteins in native PVs (i.e., serotype-specific D-antigen epitopes). Since they lack genomes and are non-infectious, PV-VLPs offer the promise of a safer, next-generation polio vaccine compared to traditional inactivated (IPV) or attenuated live (OPV) vaccines. Sandwich D-antigen ELISA formats are commonly used to measure the in vitro potency values (relative D-antigen content, DU/mL) of unadjuvanted trivalent IPV antigens. If IPV is formulated with aluminum-salt adjuvants, however, a pretreatment step (i.e., adjuvant dissolution or antigen desorption) is required, which may compromise antigen integrity during sample handling. Methods: This work describes the development of three competitive ELISAs to measure the relative D-antigen content of aluminum-salt adjuvanted PV-VLPs (Types 1, 2, 3) without the need for pretreatment. Results: First, key assay parameters were established, including specificity, accuracy, precision, linearity, limit of quantification, and stability-indication. Next, preformulation characterization studies were performed with these methods including (1) rank-ordering the inherent thermal stability profiles of the PV-VLPs (Types 1 > 3 > 2) in-solution and adsorbed to an aluminum phosphate adjuvant (AdjuPhos™, AP) and (2) determining the effect of formulation variables on the thermal stability profiles of AP-adsorbed PV-VLPs including antimicrobial preservatives (thimerosal, 2-PE) and five different antigens present in pediatric combination vaccines (D, T, wP, Hib, Hep B). Conclusions: The development and application of three competitive D-antigen ELISAs were demonstrated, and future use in formulation and storage stability studies with the AP-adjuvanted, trivalent PV-VLPs (Types 1, 2, 3) is discussed with the long-term goal to develop a stable, efficacious, multi-dose, hexavalent combination vaccine presentation. Full article
(This article belongs to the Special Issue Recent Advances in Virus-Like Particle-Based Vaccines)
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18 pages, 275 KB  
Article
Humoral and Cellular Immune Response in Patients with Hematological Disorders After Three Doses of mRNA COVID-19 Vaccine: A Single-Center Observational Study
by Rosa Daffini, Francesco Zecchini, Giulia Venneri, Michele Malagola, Chiara Cattaneo, Stefano Calza, Arnaldo Caruso, Alessandra Tucci and Cinzia Giagulli
Vaccines 2026, 14(5), 369; https://doi.org/10.3390/vaccines14050369 - 22 Apr 2026
Viewed by 874
Abstract
Background: Hematological patients have a high risk of developing severe COVID-19 (37%). Most mRNA vaccine trials in hematological patients showed a low immunogenicity after two doses, while long-term data are scarce. Methods: In this monocentric retrospective observational study, we evaluated humoral and T [...] Read more.
Background: Hematological patients have a high risk of developing severe COVID-19 (37%). Most mRNA vaccine trials in hematological patients showed a low immunogenicity after two doses, while long-term data are scarce. Methods: In this monocentric retrospective observational study, we evaluated humoral and T cell-mediated immune responses in 230 hematological patients after three doses of the Pfizer-BioNTech mRNA COVID-19 vaccine. Patients were stratified by age, disease type/state, prior COVID-19 infection, and treatment status and regimens (anti-CD20 monoclonal antibodies, BTK and BCL-2 inhibitors, and treatment line). Antibody titer to SARS-CoV-2 was assessed by electrochemiluminescence immunoassay and T cell response by QuantiFERON interferon-γ release assay (IGRA). Data were analyzed using univariate (Fisher’s exact test) and Firth’s bias-reduced penalized-likelihood logistic regression. Results: A robust humoral response was observed with 91.55% of patients developing anti-spike antibodies (GMT 988.83 U/mL). Anti-CD20-bendamustine treatment was associated with a significantly lower antibody positivity compared to untreated subjects. Prior COVID-19 infection significantly boosted both antibody positivity (95.9% vs. 85.2%) and GMT (847.02 U/mL vs. 258.79 U/mL). Conversely, T cell response was suboptimal (36.1% positive), particularly in anti-CD20-bendamustine-treated and multi-treated patients (27.1%), but highest in those treated with BTK inhibitors (50%). Multivariable logistic regression analysis linked multiple treatments to lower T cell response. Following vaccination, 29.1% of patients contracted SARS-CoV-2, but only 0.89% developed severe COVID-19. Conclusions: Three doses of mRNA vaccine elicit a strong humoral but a low T cell response, as detected by IGRA, in hematological patients. These findings underscore the importance of completing vaccination before initiating immunosuppressive therapies. Full article
(This article belongs to the Special Issue Immunization of Immunosuppressed Patients)
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24 pages, 20163 KB  
Article
Isolation, Identification, Virulence and Pathogenic Features of Lactococcus garvieae from Cage-Cultured Tilapia (Oreochromis niloticus) in Thailand
by Yosapon Adisornprasert, Benchawan Kumwan, Pakapon Meachasompop, Chonlatat Rajitdumrong, Pimrawee Chaemlek, Prapansak Srisapoome, Wararut Buncharoen, Natthapong Paankhao, Niyada Umputhorn, Chonthicha Choppradit, Pichasit Sangmek, Sittichai Hatachote, Putita Chokmangmeepisarn, Kednapat Sriphairoj and Anurak Uchuwittayakul
Int. J. Mol. Sci. 2026, 27(8), 3469; https://doi.org/10.3390/ijms27083469 - 13 Apr 2026
Viewed by 1312
Abstract
Lactococcosis caused by Lactococcus garvieae is an emerging threat to warmwater aquaculture, yet evidence integrating field outbreaks with robust molecular confirmation and controlled virulence testing remains limited for Thailand’s cage-cultured tilapia. From May to October 2025, acute mortality events were investigated in cage-cultured [...] Read more.
Lactococcosis caused by Lactococcus garvieae is an emerging threat to warmwater aquaculture, yet evidence integrating field outbreaks with robust molecular confirmation and controlled virulence testing remains limited for Thailand’s cage-cultured tilapia. From May to October 2025, acute mortality events were investigated in cage-cultured Nile tilapia (Oreochromis niloticus) in a reservoir in Ubon Ratchathani Province, Thailand. Suspected outbreaks were defined by abrupt daily mortality exceeding 5% accompanied by septicemia-like clinical signs. Water quality during sampling covered the following ranges: temperature 28.6–31.9 °C, pH 6.5–7.0, salinity 0.02–0.03 ppt, electrical conductivity 0.036–0.046 mS/cm, TDS 22.20–26.50 mg/L, total alkalinity 17.0–34.0 mg/L as CaCO3, total hardness 12.0–60.0 mg/L as CaCO3, dissolved oxygen 6.5–7.0 mg/L, and NH3 were below the limit of detection. Full-length 16S rRNA tissue profiling revealed strong tissue partitioning: blood microbiomes were consistently dominated by Lactococcus and L. garvieae at the species level, whereas gills showed higher richness and mixed communities with multiple opportunistic taxa. Culture isolation was more reliable from blood than gills, yielding 16 Gram-positive, catalase-negative isolates (AAHM-LG2501–AAHM-LG2516) that clustered within the L. garvieae clade in near full-length 16S rRNA phylogenetic analysis and were separated from closely related Lactococcus lineages. A representative blood isolate (AAHM-LG2501) showed dose-dependent virulence in controlled challenges, with an LD50 of ~1.05 × 105 CFU/fish by intraperitoneal injection and an LC50 of ~1.20 × 106 CFU/mL by immersion. Histopathology supported systemic dissemination, with injection producing more consistent multi-organ lesions than immersion, particularly in head kidney, liver, and spleen, while gills exhibited route-associated epithelial and vascular alterations. Together, these findings confirm L. garvieae as a major etiological agent of septicemic outbreaks in cage-cultured tilapia in Thailand and support a practical surveillance framework prioritizing blood sampling, molecular confirmation, and risk-based monitoring to guide biosecurity and vaccine-oriented prevention. Full article
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21 pages, 704 KB  
Review
Tetanus Control in the United States and Global Disaster Settings: Public Health Disparities and Prevention Strategies
by Olivia Stala, Suhana Patel, Christian Donlon, Syed Shehroz Hussain, Rahim Hirani and Mill Etienne
Medicina 2026, 62(2), 338; https://doi.org/10.3390/medicina62020338 - 7 Feb 2026
Cited by 1 | Viewed by 3321
Abstract
Tetanus, a disease caused by the neurotoxin-producing bacteria Clostridium tetani (C. tetani), remains a serious threat, particularly among individuals who are unvaccinated or under-vaccinated. Although public health guidelines in the United States continue to recommend a well-established, multi-dose vaccination schedule to [...] Read more.
Tetanus, a disease caused by the neurotoxin-producing bacteria Clostridium tetani (C. tetani), remains a serious threat, particularly among individuals who are unvaccinated or under-vaccinated. Although public health guidelines in the United States continue to recommend a well-established, multi-dose vaccination schedule to prevent tetanus, recent revisions to the Centers for Disease Control and Prevention webpage language on vaccine safety prompted renewed public discussion. Despite this, extensive evidence continues to demonstrate the effectiveness and safety of tetanus immunization, and certain demographic groups remain disproportionately at risk. Globally and within the United States, natural disaster zones remain especially high-risk environments for tetanus infection. This review examines the pathophysiology of tetanus, current vaccination recommendations, and the social and geographic inequities that influence vaccine uptake. It also evaluates strategies of protection and prevention. Particular emphasis is placed on tetanus risk in disaster settings, where disrupted infrastructure, greater likelihood of contaminated wounds, and preexisting disparities in vaccination coverage compound vulnerability. A clearer understanding of these factors is essential for strengthening public health preparedness and ensuring equitable protection against tetanus, especially for populations disproportionately affected by disasters. Full article
(This article belongs to the Section Epidemiology & Public Health)
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23 pages, 1767 KB  
Systematic Review
Efficacy and Safety of mRNA-Based COVID-19 Vaccines in Solid Organ Transplant Recipients: A Systematic Review and Meta-Analysis
by Maya Alkhidir and Kannan Sridharan
Vaccines 2026, 14(1), 72; https://doi.org/10.3390/vaccines14010072 - 8 Jan 2026
Cited by 1 | Viewed by 1948
Abstract
Background: Solid organ transplant recipients (SOTRs) are highly vulnerable to severe COVID-19 infection, yet initial vaccine trials provided limited data on efficacy and safety in this immunocompromised population. Heterogeneous seroconversion rates and conflicting safety reports complicate the formulation of clear clinical guidelines. This [...] Read more.
Background: Solid organ transplant recipients (SOTRs) are highly vulnerable to severe COVID-19 infection, yet initial vaccine trials provided limited data on efficacy and safety in this immunocompromised population. Heterogeneous seroconversion rates and conflicting safety reports complicate the formulation of clear clinical guidelines. This systematic review and meta-analysis aim to aggregate existing evidence to determine the precise seroconversion and safety profiles of COVID-19 vaccines and identify key factors influencing immune response in SOTRs. Methods: A comprehensive literature search was conducted identifying 125 studies evaluating WHO/FDA-authorized vaccines in SOTRs. Outcomes were the pooled seroconversion proportion and safety profile. Subgroup analyses were performed based on vaccine type, transplanted organ, number of doses, and prior SARS-CoV-2 infection status, confirmed by leave-one-out sensitivity analysis and bootstrap methods. Results: Most studies assessed mRNA-based vaccines (123/125, 98.4%). The overall pooled seroconversion proportion across all SOTRs was significantly blunted at 0.49 (95% CI, 0.43 to 0.55), demonstrating high heterogeneity (I2 = 94.2%). Seroconversion showed a clear positive dose–response relationship, increasing from 27% after one dose to 84% after four doses. Prior COVID-19 infection was the strongest predictor of a response, resulting in a pooled seroconversion of 0.90 (95% CI, 0.82 to 0.94; I2 = 0%). Organ-specific analyses revealed the highest response in Liver recipients (0.80) and the lowest in Lung recipients (0.29). Vaccine platform analysis showed that the highest response was with mRNA-1273 (0.55) and the lowest with CoronaVac (0.29). The safety profile was limited. Conclusions: SOTRs exhibit profound hypo responsiveness to COVID-19 vaccines; however, the extreme heterogeneity observed across studies necessitates a cautious interpretation of pooled seroconversion estimates. While the data indicates a significant dose–response relationship favoring an aggressive, multi-dose strategy, the apparent safety profile may reflect under-reporting and limited follow-up rather than confirmed safety equivalence. Rare but clinically critical outcomes, such as acute allograft rejection, remain inadequately characterized in the current literature. Consequently, while the prioritization of multi-dose regimens and hybrid immunity is supported to maximize protection, clinicians must recognize that individual responses remain highly variable, and the long-term immunological impact of repeated stimulation requires further standardized investigation. Full article
(This article belongs to the Special Issue Immunization of Immunosuppressed Patients)
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18 pages, 1970 KB  
Article
Systematic Development and Validation of a Bradford-Based Protein Quantification Method for Novel Multi-Dose R21 Malaria Vaccine Formulated with 2-Phenoxy Ethanol (2-PE)
by Rajender Jena, Dnyanesh Ranade, Prajwal Chaudhari, Ajay Salunke, Aniket Mahamuni and Sunil Gairola
Vaccines 2026, 14(1), 25; https://doi.org/10.3390/vaccines14010025 - 24 Dec 2025
Cited by 2 | Viewed by 2437
Abstract
Background: The R21 malaria vaccine is a next-generation, WHO-prequalified vaccine that was introduced to reduce the burden of clinical malaria. In alignment with WHO recommendations, multi-dose vaccine presentations are preferred for large-scale immunization and inclusion in the Expanded Programme on Immunization (EPI). Accurate [...] Read more.
Background: The R21 malaria vaccine is a next-generation, WHO-prequalified vaccine that was introduced to reduce the burden of clinical malaria. In alignment with WHO recommendations, multi-dose vaccine presentations are preferred for large-scale immunization and inclusion in the Expanded Programme on Immunization (EPI). Accurate protein quantification is a critical quality control parameter for lot release, but it remains challenging when the antigen is present at low protein concentrations or formulated with complex matrices, including adjuvants, stabilizers, and preservatives. Methods: In this study, multiple protein estimation methods including Micro-BCA, BCA, and Bradford assays were evaluated to determine their suitability for quantifying the R21 antigen formulated with Matrix-M1 adjuvant and 2-PE preservative. The Bradford assay was selected as the most appropriate method, based on a comparative assessment of precision, accuracy, and linearity. Further optimization was undertaken to identify suitable buffer systems, and the method was validated in accordance with ICH Q2(R2) guidelines. Results: Validation results demonstrated that the assay is specific, accurate, precise, and repeatable, with a limit of quantitation (LOQ) of 2 µg/mL. The method demonstrated comparable performance to ELISA and was found to be sensitive enough to detect changes in antigen concentration resulting from unintended adsorption of R21 to vial surfaces. The assay offers a rapid, high-throughput, and cost-effective solution for protein quantitation in commercial manufacturing, lot release, and stability studies. The protein content of the drug product, quantified using the Bradford method, demonstrated robust in vivo immunogenicity in both release and stability studies. Conclusions: The robustness and reproducibility of the assay establish a new benchmark in quality control for virus-like particle (VLP)-based vaccines with complex formulations, thereby supporting the precision and reliability required for global malaria prevention efforts. Full article
(This article belongs to the Special Issue Recent Advances in Malaria Vaccine Development—2nd Edition)
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23 pages, 564 KB  
Perspective
Advances in Drug and Vaccine Delivery for Low- and Middle-Income Healthcare Programs—The Case for Replacing Multi-Dose Vials with Prefilled Single-Dose Delivery Systems
by Darin Zehrung and Michael J. Free
Pharmacy 2025, 13(6), 180; https://doi.org/10.3390/pharmacy13060180 - 10 Dec 2025
Viewed by 2620
Abstract
The transition toward wide-scale use of single-dose administration systems such as prefilled syringes has primarily occurred in high-income countries due to economic considerations. This has resulted in a disparity of access to such technologies in low- and middle-income countries, which continue to utilize [...] Read more.
The transition toward wide-scale use of single-dose administration systems such as prefilled syringes has primarily occurred in high-income countries due to economic considerations. This has resulted in a disparity of access to such technologies in low- and middle-income countries, which continue to utilize multi-dose vial-based presentations and syringes for parenteral delivery. Single-dose innovations currently available or in the product development pipeline represent the promise of enhanced access globally and the potential for public health impact. This perspective article discusses the reported benefits of pre-filled single-dose delivery systems compared to multi-dose vials, as well as the higher standards of infection control regulations and practices that resulted in the increasing use of and benefit from single-dose administration systems in high-income countries. We evaluated how these benefits and standards could enhance health initiatives in low- and middle-income countries. Finally, we explored the potential for making pre-filled single-dose delivery methods both accessible and affordable in low- and middle-income countries. Full article
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19 pages, 308 KB  
Article
HPV Vaccination in the U.S. Midwest: Barriers and Facilitators of Initiation and Completion in Adolescents and Young Adults
by Kristyne D. Mansilla Dubon, Edward S. Peters, Shinobu Watanabe-Galloway and Abraham Degarege
Vaccines 2025, 13(11), 1175; https://doi.org/10.3390/vaccines13111175 - 20 Nov 2025
Cited by 2 | Viewed by 2046
Abstract
Background/Objectives: HPV vaccination uptake among adolescents and young adults in the US remains low, and coverage in the Midwest falls short of the Healthy People 2030 goal of 80%. Methods: A cross-sectional survey of adolescents and young adults was conducted to [...] Read more.
Background/Objectives: HPV vaccination uptake among adolescents and young adults in the US remains low, and coverage in the Midwest falls short of the Healthy People 2030 goal of 80%. Methods: A cross-sectional survey of adolescents and young adults was conducted to identify facilitators and barriers to HPV vaccination uptake among adolescents and young adults in the Midwest. Results: Out of 1306 individuals aged 13–26 years, 397 (30.4%) were fully vaccinated (2–3 doses), 124 (9.5%) had received one dose, 324 (24.8%) were unvaccinated, and 461 (35.3%) were unsure of their vaccination status. Awareness of HPV vaccines (OR: 2.4, 95% CI: 1.6, 3.6), beliefs about vaccine effectiveness (OR: 1.8, 95% CI: 1.1, 2.9), family support (OR: 2.3 95% CI: 1.4, 3.8) and knowing someone with cervical cancer (OR: 1.8, 95% CI: 1.2, 2.7) were associated with increased odds of full vaccination. Beliefs in vaccine safety (OR: 2.0, 95%CI: 1.0, 3.9) and having health insurance coverage (OR: 1.9, 95% CI: 1.0, 3.5) were associated with increased odds of initiated vaccination (i.e., receiving at least one dose). Concerns about vaccine side effects (OR: 0.5, 95% CI: 0.3, 0.8) and not receiving recommendations from doctors were significantly associated with decreased odds of full vaccination (OR: 0.5, 95% CI: 0.3, 0.8) or initiated vaccination (OR: 0.5% CI: 0.2, 0.9). Clinician recommendations and awareness also reduced the likelihood of unknown vaccination status. Race-stratified analyses suggested heterogeneity in predictors across racial/ethnic groups. Conclusions: Our findings support the need for multi-level interventions aimed at increasing HPV vaccination initiation and completion in the Midwest. Full article
(This article belongs to the Special Issue Acceptance and Hesitancy in Vaccine Uptake: 2nd Edition)
11 pages, 875 KB  
Article
Waning Protection Against Severe COVID-19 Following Vaccination: A Longitudinal IPTW Analysis of Emergency Department Encounters
by Yuying Xing and Amit Bahl
Infect. Dis. Rep. 2025, 17(6), 142; https://doi.org/10.3390/idr17060142 - 13 Nov 2025
Viewed by 1421
Abstract
Background: The duration of protection that COVID-19 vaccination provides against severe outcomes remains uncertain. Accurately defining this timeframe is critical for informing effective vaccination policies and booster strategies. This investigation aimed to quantify the length and durability of vaccine-conferred protection against severe disease, [...] Read more.
Background: The duration of protection that COVID-19 vaccination provides against severe outcomes remains uncertain. Accurately defining this timeframe is critical for informing effective vaccination policies and booster strategies. This investigation aimed to quantify the length and durability of vaccine-conferred protection against severe disease, delivering evidence to guide public health decision-making. Methods: We conducted a multi-site cohort study to evaluate the relationship between time since last COVID-19 vaccination and the risk of severe infection among emergency department (ED) patients with a principal diagnosis of COVID-19. Vaccination status was categorized by time since the last documented dose: unvaccinated, 0–6 months, 7–12 months, 13–18 months, and 19–24 months. The primary outcome was severe COVID-19, defined as ICU admission, mechanical ventilation, or in-hospital death. Inverse Probability of Treatment Weighting (IPTW) was used to adjust for baseline confounding based on age group, sex, race, comorbidity burden, immunocompromised status, and calendar time period (pre-2023 vs. post-2023). Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for each vaccination interval compared to unvaccinated patients. Results: Between 1 December 2021, and 20 July 2024, 42,124 ED encounters were included in the analysis. In IPTW-weighted models, vaccination within 0–6 months (aHR 0.73, 95% CI 0.64–0.83), 7–12 months (aHR 0.72, 95% CI 0.64–0.82), and 13–18 months (aHR 0.67, 95% CI 0.57–0.79) was associated with a significantly reduced risk of severe outcomes. However, no significant protection was observed at 19–24 months (aHR 0.95, 95% CI 0.80–1.14). In age-stratified analyses, protection persisted longer in individuals aged ≥65 years than in those aged 50–64. Older age, male sex, comorbidities, and immunocompromised status were also associated with increased risk. Conclusions: COVID-19 vaccination provides sustained protection against severe outcomes for up to 18 months, after which effectiveness declines substantially. These findings support booster dose strategies based on time since last vaccination and targeted prioritization for high-risk populations. Full article
(This article belongs to the Section Immunology and Vaccines)
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27 pages, 2600 KB  
Review
Redefining the Diagnostic and Therapeutic Landscape of Non-Small Cell Lung Cancer in the Era of Precision Medicine
by Shumayila Khan, Saurabh Upadhyay, Sana Kauser, Gulam Mustafa Hasan, Wenying Lu, Maddison Waters, Md Imtaiyaz Hassan and Sukhwinder Singh Sohal
J. Clin. Med. 2025, 14(22), 8021; https://doi.org/10.3390/jcm14228021 - 12 Nov 2025
Cited by 13 | Viewed by 3814
Abstract
Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality globally, driven by marked molecular and cellular heterogeneity that complicates diagnosis and treatment. Despite advances in targeted therapies and immunotherapies, treatment resistance frequently emerges, and clinical benefits remain limited to specific [...] Read more.
Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality globally, driven by marked molecular and cellular heterogeneity that complicates diagnosis and treatment. Despite advances in targeted therapies and immunotherapies, treatment resistance frequently emerges, and clinical benefits remain limited to specific molecular subtypes. To improve early detection and dynamic monitoring, novel diagnostic strategies—including liquid biopsy, low-dose computed tomography scans (CT) with radiomic analysis, and AI-integrated multi-modal platforms—are under active investigation. Non-invasive sampling of exhaled breath, saliva, and sputum, and high-throughput profiling of peripheral T-cell receptors and immune signatures offer promising, patient-friendly biomarker sources. In parallel, multi-omic technologies such as single-cell sequencing, spatial transcriptomics, and proteomics are providing granular insights into tumor evolution and immune interactions. The integration of these data with real-world clinical evidence and machine learning is refining predictive models and enabling more adaptive treatment strategies. Emerging therapeutic modalities—including antibody–drug conjugates, bispecific antibodies, and cancer vaccines—further expand the therapeutic landscape. This review synthesizes recent advances in NSCLC diagnostics and treatment, outlines key challenges, and highlights future directions to improve long-term outcomes. These advancements collectively improve personalized and effective management of NSCLC, offering hope for better-quality survival. Continued research and integration of cutting-edge technologies will be crucial to overcoming current challenges and achieving long-term clinical success. Full article
(This article belongs to the Section Oncology)
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14 pages, 288 KB  
Article
Factors Associated with Missed Opportunities for Vaccination in Children During the First Year of Life: A Cross-Sectional Study
by Wágnar Silva Morais Nascimento, Eugênio Barbosa de Melo Júnior, Ana Raisla de Araújo Rodrigues, Beatriz Mourão Pereira, Joaquim Guerra de Oliveira Neto, Paulo de Tarso Moura Borges, Antonio Rosa de Sousa Neto and Telma Maria Evangelista de Araújo
Vaccines 2025, 13(11), 1129; https://doi.org/10.3390/vaccines13111129 - 1 Nov 2025
Cited by 1 | Viewed by 2368
Abstract
Background: Addressing Missed Opportunities for Vaccination (MOV) contributes to increased vaccination rates in children, reinforcing the need to investigate and intervene in the related factors. Objective: To analyze factors associated with missed opportunities for vaccination in children under one year of age in [...] Read more.
Background: Addressing Missed Opportunities for Vaccination (MOV) contributes to increased vaccination rates in children, reinforcing the need to investigate and intervene in the related factors. Objective: To analyze factors associated with missed opportunities for vaccination in children under one year of age in a Brazilian capital. Methods: This was a cross-sectional, analytical study conducted in seven Basic Health Units in Teresina, Piauí, Brazil. A previously validated questionnaire was applied to parents or guardians of a sample of 316 children. Data were collected from March to June 2025. Multivariable Logistic Regression was performed, and results were expressed as Odds Ratios. Results: Among the children, 53.5% had at least one MOV. The associated factors were: parents with two or more children (95% CI: 1.06–2.96), false contraindications (95% CI: 1.29–8.73), inadequate assessment of vaccination cards by health professionals (95% CI: 1.78–29.00), vaccine shortages in health units (95% CI: 1.57–18.28), and refusal to open multidose vaccine vials (95% CI: 1.81–19.31). Receiving information about vaccination in the previous month was a protective factor against MOV (95% CI: 0.25–0.77). The vaccines most frequently contributing to MOV were BCG (15.8%) and the COVID-19 vaccine, with 15.5% for the first dose and 14.9% for the second. Conclusions: The high prevalence of MOV found in this study indicates weaknesses in the immunization process and suggests the need for implementing measures to interrupt the chain of causes leading to MOV, thereby contributing to the achievement of the objectives of the Brazilian National Immunization Program. Full article
(This article belongs to the Special Issue The Role of Vaccination on Public Health and Epidemiology)
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