Vaccines

18 pages, 2527 KiB

Open AccessArticle

Targeting Azole-Resistant Candida albicans: Tetrapeptide Tuftsin-Modified Liposomal Vaccine Induces Superior Immune Protection

by Masood A. Khan, Arif Khan, Abdullah M. Alnuqaydan, Aqel Albutti, Basmah F. Alharbi and Mohammad Owais

Vaccines 2025, 13(6), 630; https://doi.org/10.3390/vaccines13060630 - 11 Jun 2025

Abstract

Background/objectives: Candida albicans is a major fungal pathogen that poses a serious threat to immunocompromised individuals. The increasing prevalence of fluconazole-resistant strains presents a critical clinical challenge, emphasizing the urgent need for novel therapeutic strategies. This study aimed to evaluate the prophylactic potential [...] Read more.

Background/objectives: Candida albicans is a major fungal pathogen that poses a serious threat to immunocompromised individuals. The increasing prevalence of fluconazole-resistant strains presents a critical clinical challenge, emphasizing the urgent need for novel therapeutic strategies. This study aimed to evaluate the prophylactic potential of a new liposomal vaccine formulation, Tuft-lip-WCAgs, comprising Tuftsin and C. albicans whole cell antigens, in providing immune protection against systemic candidiasis. Methods: The vaccine formulation was tested in a murine model of systemic C. albicans infection. The efficacy of the Tuft-lip-WCAg vaccine was evaluated through a survival analysis, fungal burden assessments, and immunological profiling. Immune responses were assessed by measuring serum antibody titers and isotypes, T cell proliferation, and cytokine secretion (IFN-γ and IL-4) from splenocytes. Results: FLZ treatment showed weak antifungal activity, high MIC values, and limited biofilm disruption and failed to ensure long-term survival, resulting in 100% mortality by day 40. In contrast, Tuft-lip-WCAg vaccination was well tolerated and conferred complete protection, with no detectable fungal burden by day 40. Vaccinated mice exhibited significantly elevated total antibody titers (166,667 ± 14,434), increased IgG2a levels, and enhanced T cell proliferation (stimulation index: 3.9 ± 0.84). Splenocytes from immunized mice secreted markedly higher levels of IFN-γ (634 ± 128 pg/mL) and IL-4 (582 ± 82 pg/mL), indicating a balanced Th1/Th2 immune response. Tuft-lip-WCAg vaccination also achieved 100% survival and the lowest kidney fungal burden (556 ± 197 CFUs/g). Conclusions: Tuft-lip-WCAg formulation is a safe, immunogenic, and highly effective vaccine candidate that offers complete protection against drug-resistant C. albicans in a murine model. These findings support its promise as a novel immunoprophylactic strategy, particularly for immunocompromised populations at high risk of invasive candidiasis. Full article

(This article belongs to the Special Issue Peptide-Based Vaccines)

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19 pages, 1427 KiB

Open AccessArticle

Citrullinated ENO1 Vaccine Enhances PD-1 Blockade in Mice Implanted with Murine Triple-Negative Breast Cancer Cells

by Ricardo A. León-Letelier, Alejandro M. Sevillano-Mantas, Yihui Chen, Soyoung Park, Jody Vykoukal, Johannes F. Fahrmann, Edwin J. Ostrin, Candace Garrett, Rongzhang Dou, Yining Cai, Fu-Chung Hsiao, Jennifer B. Dennison, Eduardo Vilar, Banu K. Arun, Samir Hanash and Hiroyuki Katayama

Vaccines 2025, 13(6), 629; https://doi.org/10.3390/vaccines13060629 - 11 Jun 2025

Abstract

Background/Objectives:Cancer vaccine targets mostly include mutations and overexpressed proteins.vHowever, cancer-associated post-translational modifications (PTMs) may also induce immune responses. Previously, our group established the enzyme protein arginine deiminase type-2 (PADI2), which catalyzes citrullination modification, is highly expressed in triple-negative breast cancer (TNBC), promoting [...] Read more.

Background/Objectives:Cancer vaccine targets mostly include mutations and overexpressed proteins.vHowever, cancer-associated post-translational modifications (PTMs) may also induce immune responses. Previously, our group established the enzyme protein arginine deiminase type-2 (PADI2), which catalyzes citrullination modification, is highly expressed in triple-negative breast cancer (TNBC), promoting antigenicity. Methods: Here, we show the workflow of designing citrullinated enolase 1 (citENO1) vaccine peptides identified from breast cancer cells by mass spectrometry and demonstrate TNBC vaccine efficacy in the mouse model. Immunized mice with citENO1 peptides or the corresponding unmodified peptides, plus Poly I:C as an adjuvant, were orthotopically implanted with a TNBC murine cell line. Results: Vaccination with citENO1, but not unmodified ENO1 (umENO1), induced a greater percentage of activated CD8+ PD-1+ T cells and effector memory T cells in skin-draining lymph nodes (SDLNs). Remarkably, the citENO1 vaccine delayed tumor growth and prolonged overall survival, which was further enhanced by PD-1 blockade. Conclusions: Our data suggest that cancer-restricted post-translational modifications provide a source of vaccines that induce an anti-cancer immune response. Full article

(This article belongs to the Special Issue Personalised Cancer Vaccines)

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20 pages, 2626 KiB

Open AccessArticle

Development of an Influenza/COVID-19 Combination mRNA Vaccine Containing a Novel Multivalent Antigen Design That Enhances Immunogenicity of Influenza Virus B Hemagglutinins

by Elena Thornhill-Wadolowski, Dana L. Ruter, Feng Yan, Mayur Gajera, Evan Kurt, Labannya Samanta, Kimberlin Leigh, Jianbo Zhu, Zhijun Guo, Zihao Wang, Yuanqing Liu, Jaewoo Lee and Marcin Bugno

Vaccines 2025, 13(6), 628; https://doi.org/10.3390/vaccines13060628 - 11 Jun 2025

Abstract

Background/Objectives: Developing next-generation mRNA-based seasonal influenza vaccines remains challenging, primarily because of the relatively low immunogenicity of influenza B hemagglutinin (HA) antigens. We describe a systematic vaccine development strategy that combined vector and antigen design optimization. Methods: Novel untranslated region (UTR) sequences and [...] Read more.

Background/Objectives: Developing next-generation mRNA-based seasonal influenza vaccines remains challenging, primarily because of the relatively low immunogenicity of influenza B hemagglutinin (HA) antigens. We describe a systematic vaccine development strategy that combined vector and antigen design optimization. Methods: Novel untranslated region (UTR) sequences and a hybrid poly(A) tail were used to increase plasmid stability and mRNA expression. Fusion proteins containing HA antigens linked by T4 foldon domains were engineered to enhance the immune responses against influenza B HA antigens and to permit the expression of multiple HA ectodomains from a single mRNA species. The vaccine performance was verified in a traditional encapsulated lipid nanoparticle (LNP) formulation that requires long-term storage at temperatures below −15 °C as well as in a proprietary thermo-stable LNP formulation developed for the long-term storage of the mRNA vaccine at 2–8 °C. Results: In preclinical studies, our next-generation seasonal influenza vaccine tested alone or as a combination influenza/COVID-19 mRNA vaccine elicited hemagglutination inhibition (HAI) titers significantly higher than Fluzone HD, a commercial inactivated influenza vaccine, across all 2024/2025 seasonal influenza strains, including the B/Victoria lineage strain. At the same time, the combination mRNA vaccine demonstrated superior neutralizing antibody titers to 2023/2024 Spikevax, a commercial COVID-19 comparator mRNA vaccine. Conclusions: Our data demonstrate that the multimerization of antigens expressed as complex fusion proteins is a powerful antigen design approach that may be broadly applied toward mRNA vaccine development. Full article

(This article belongs to the Section DNA and mRNA Vaccines)

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19 pages, 1915 KiB

Open AccessReview

Predicting the Epidemiological Effects in the United Kingdom of Moving from PCV13 to PCV15 in the Routine Pediatric 1 + 1 Vaccination Schedule

by Rachel J. Oidtman, Natalie Banniettis, Jessica Weaver, Ian R. Matthews, Dionysios Ntais, Giulio Meleleo, Tufail M. Malik, John C. Lang and Oluwaseun Sharomi

Vaccines 2025, 13(6), 627; https://doi.org/10.3390/vaccines13060627 - 10 Jun 2025

Abstract

Background/Objectives: Pneumococcal conjugate vaccines (PCVs) were first introduced in the pediatric UK National Immunization Programme (NIP) in 2006 and subsequently led to a significant decline in invasive pneumococcal disease (IPD). In 2020, the UK NIP reduced the pediatric PCV dosing schedule from two [...] Read more.

Background/Objectives: Pneumococcal conjugate vaccines (PCVs) were first introduced in the pediatric UK National Immunization Programme (NIP) in 2006 and subsequently led to a significant decline in invasive pneumococcal disease (IPD). In 2020, the UK NIP reduced the pediatric PCV dosing schedule from two infant doses and one toddler dose (2 + 1) to one infant dose and one toddler dose (1 + 1). This analysis evaluated the public health impact of pediatric vaccination with PCV15 versus PCV13 under a 1 + 1 schedule. Methods: A population-level compartmental model was previously adapted to the UK setting. The impact on the IPD incidence of vaccination with PCV15 versus PCV13 under a 1 + 1 schedule was evaluated over a 20-year time horizon. The uncertainty regarding the vaccine efficacy (VE) of PCV13 and PCV15 under a 1 + 1 schedule was investigated through a probabilistic sensitivity analysis, i.e., the PCV VE under a 1 + 1 schedule was assumed to be 0–24% lower than the PCV VE under a 2 + 1 schedule. Results: Relative to the initial IPD incidence, vaccination with PCV13 and PCV15 under a 1 + 1 schedule resulted in the IPD incidence in children <2 years old increasing by 11.1% (95% region: 8.4–14.5%) and 3.5% (0.2–7.7%), respectively, over the time horizon. At the end of the time horizon, in the overall population, PCV15 would lead to a 6.0% lower IPD incidence than PCV13 (10.70 IPD cases per 100,000 versus 11.38 per 100,000, respectively). Conclusions: Switching from PCV13 to PCV15 for routine pediatric vaccinations under the 1 + 1 dosing schedule in the UK led to a lower IPD incidence in both the pediatric and overall populations. Full article

(This article belongs to the Special Issue Pneumococcal Vaccines: Current Status and Future Prospects)

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22 pages, 3342 KiB

Open AccessArticle

A High-Throughput and Robust Relative Potency Assay Measuring Human Cytomegalovirus Infection in Epithelial Cells for Vaccine Development

by Nicole M. Smiddy, Nisarg Patel, Matthew C. Troutman, Kristine M. Kearns, Zachary P. Davis, Christopher S. Adams, Carl Hofmann, Donald J. Warakomski, Harrison Davis, Daniel Spatafore, Adam Kristopeit, Pete DePhillips and John W. Loughney

Vaccines 2025, 13(6), 626; https://doi.org/10.3390/vaccines13060626 - 10 Jun 2025

Abstract

Background/Objectives: A preventative vaccine against human cytomegalovirus (HCMV) infection and disease remains an unmet medical need. Several attenuated virus and antigen-based HCMV vaccine candidates have been proposed; however, development challenges have limited their progression through the clinical pipeline. Method: A high-throughput and robust [...] Read more.

Background/Objectives: A preventative vaccine against human cytomegalovirus (HCMV) infection and disease remains an unmet medical need. Several attenuated virus and antigen-based HCMV vaccine candidates have been proposed; however, development challenges have limited their progression through the clinical pipeline. Method: A high-throughput and robust relative potency assay, Imaging of Relative Viral Expression (IRVE), was developed and applied to measure the infection of a live-attenuated HCMV vaccine candidate in ARPE-19 epithelial cells. The IRVE assay measures HCMV infection by immunostaining Immediate Early 1 (IE1) protein and enumeration of IE1-positive, infected cells against total cells. Increased throughput was accomplished using 384-well plate automation on a custom-designed integrated robotic system. Results: The IRVE assay effectively measures relative potency changes in an HCMV vaccine candidate under different upstream processes, downstream processes, and formulation conditions. Key assay parameters including microplate format, cell density, serum concentration, infection time and influence of cell age were evaluated and optimized. The IRVE assay was correlated to historical, lower throughput HCMV potency assays, including plaque and Infectivity of Early Gene Expression (IEE), validating its application as a potency screening tool. Conclusions: The IRVE assay has been successfully implemented to support HCMV vaccine development over several years of clinical development. Full article

(This article belongs to the Special Issue Innovations in Vaccine Technology)

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23 pages, 4903 KiB

Open AccessArticle

Highly Effective mRNA-LNP Vaccine Against Respiratory Syncytial Virus (RSV) in Multiple Models

by Huarong Bai, Xueliang Yu, Yue Gao, Qin Li, Baigang Wen and Rongkuan Hu

Vaccines 2025, 13(6), 625; https://doi.org/10.3390/vaccines13060625 - 10 Jun 2025

Abstract

Background: The transmembrane fusion (F) protein of RSV plays important roles in RSV pathogenesis as it mediates the fusion between the virus and the target cell membrane. During the fusion process, the F protein transits from a metastable state (prefusion, preF) to a [...] Read more.

Background: The transmembrane fusion (F) protein of RSV plays important roles in RSV pathogenesis as it mediates the fusion between the virus and the target cell membrane. During the fusion process, the F protein transits from a metastable state (prefusion, preF) to a stable state (postfusion, postF) after the merging of the virus and cell membranes. The majority of highly neutralizing antibodies induced by natural infection or immunization target the preF form, which makes it the preferred antigen for vaccine development. Methods: Here, we designed an effective RSV mRNA vaccine, STR-V003, consisting of mRNA encoding preF protein in lipid nanoparticles (LNPs). The immunogenicity, protection efficacy and toxicity were measured in multiple animal models. Results: STR-V003 demonstrated robust immunogenicity in both mice and cotton rats, inducing high levels of neutralizing antibodies and RSV preF-specific IgG antibodies and significantly reducing the RSV viral loads in the lung and nose tissue of challenged animals. In addition, STR-V003 did not show significant enhancement of lung pathology without causing vaccine-enhanced disease (VED). The repeated dose general toxicology studies and local tolerance studies of STR-V003 were evaluated in rats and non-human primate (NHP). Conclusions: STR-V003 demonstrates a favorable safety profile and induces robust protective immunity against RSV. Full article

(This article belongs to the Special Issue The Development of mRNA Vaccines)

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28 pages, 543 KiB

Open AccessSystematic Review

Mapping Behavioral and Social Drivers of Influenza Vaccine Uptake in Older Adults: A Scoping Review

by Enming Zhang, Shuhui Shang, Yufei Xing, Jiasong Cui, Chen Pan, Holly Seale and Qiong Fang

Vaccines 2025, 13(6), 624; https://doi.org/10.3390/vaccines13060624 (registering DOI) - 10 Jun 2025

Abstract

Background/Objectives: Influenza vaccination plays a crucial role in reducing morbidity and mortality among older adults; however, uptake remains suboptimal, particularly in the post-COVID-19 pandemic. In many settings, countries have not recovered their influenza vaccine coverage rates to the same level as pre-COVID. Therefore, [...] Read more.

Background/Objectives: Influenza vaccination plays a crucial role in reducing morbidity and mortality among older adults; however, uptake remains suboptimal, particularly in the post-COVID-19 pandemic. In many settings, countries have not recovered their influenza vaccine coverage rates to the same level as pre-COVID. Therefore, this scoping review systematically identified the behavioral and social drivers (BeSD) influencing influenza vaccination among older adults using the BeSD framework. Methods: A systematic search across five databases included quantitative, qualitative, and mixed-methods studies involving individuals aged 60 years and older. Data were charted across four BeSD domains: thinking and feeling, social processes, motivation, and practical issues. Results: Thirty-nine studies from 24 countries were included. Key barriers encompassed safety concerns, misinformation, financial burdens, logistical challenges, and cultural and language barriers. While motivation was positively associated with vaccination intentions, the transition from intention to behavior remains underexplored, and practical issues have received comparatively limited research attention. Conclusions: These findings underscore the need for multifaceted, behaviorally informed interventions and greater inclusion of under-resourced settings to support equitable influenza vaccination strategies for healthy aging. Full article

(This article belongs to the Special Issue Vaccination in a Post-Pandemic World)

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12 pages, 426 KiB

Open AccessArticle

Post-Marketing Surveillance of Nirsevimab: Safety Profile and Adverse Event Analysis from Spain’s 2023–2024 RSV Immunisation Campaign

by Pablo Estrella-Porter, Elisa Correcher-Martínez, Alejandro Orrico-Sánchez and Juan José Carreras

Vaccines 2025, 13(6), 623; https://doi.org/10.3390/vaccines13060623 (registering DOI) - 10 Jun 2025

Abstract

Background: Respiratory syncytial virus (RSV) poses a significant health burden in children, being the major cause of lower respiratory tract infection (LRTI), including bronchiolitis. During the 2023–2024 RSV season, Spain introduced nirsevimab, a monoclonal antibody for universal RSV prophylaxis in infants. This study [...] Read more.

Background: Respiratory syncytial virus (RSV) poses a significant health burden in children, being the major cause of lower respiratory tract infection (LRTI), including bronchiolitis. During the 2023–2024 RSV season, Spain introduced nirsevimab, a monoclonal antibody for universal RSV prophylaxis in infants. This study reviews the safety of nirsevimab through post-marketing surveillance. Material and Methods: A descriptive pharmacovigilance study was made based on spontaneous reporting data of suspected adverse events (SAEs) from the Spanish Pharmacovigilance System for Medicinal Products for Human Use (SEFV-H) and industry reports. SAEs reported between September 2023 and May 2024 were extracted from the Spanish Pharmacovigilance Adverse Reactions Data (FEDRA) database. Cases were analysed by sex, age, severity, and SAEs classification using the Preferred Terms (PT) level of the Medical Dictionary for Regulatory Activities (MedDRA). Reporting rates were estimated based on immunization coverage and birth data. Results: Sixty-seven cases reported 141 SAEs, yielding an overall rate of 23.1 cases per 100,000 doses. Common events included rash (8.51%), drug ineffectiveness (7.09%), and pyrexia (7.09%). Serious events constituted 53.70% of reports, including two fatalities (3.00%). No new safety signals or unexpected risks, such as antibody-dependent enhancement (ADE), were identified. Discussion: SAEs reported peaked early in the campaign, reflecting heightened reporting in new immunization programs. The safety profile aligns with clinical trial findings and regulatory expectations, confirming nirsevimab’s benefit–risk balance. Continued pharmacovigilance is critical for maintaining public trust in RSV prophylaxis. Nirsevimab demonstrated a favorable safety profile during Spain’s initial universal RSV immunization campaign in infants, supporting its continued use in reducing RSV-related morbidity. Full article

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17 pages, 636 KiB

Open AccessArticle

A Multi-Center Study on Sensitization to Thimerosal in North-Eastern Italy, 1997–2023: Prevalence, Risk Factors, the Role of Occupation and the Impact of Vaccinations

by Luca Cegolon, Emilia Patriarca and Francesca Larese Filon

Vaccines 2025, 13(6), 622; https://doi.org/10.3390/vaccines13060622 - 9 Jun 2025

Abstract

Background: Thimerosal has been widely used as a preservative to prevent microbial growth in medications and vaccines. However, in 1999 its removal from vaccine formulations was called for due to concerns about its potential side effects on humans, with subsequent reduced sensitizations [...] Read more.

Background: Thimerosal has been widely used as a preservative to prevent microbial growth in medications and vaccines. However, in 1999 its removal from vaccine formulations was called for due to concerns about its potential side effects on humans, with subsequent reduced sensitizations at patch tests. The present multi-center study investigated the epidemiological, occupational and temporal pattern of sensitization to Thimerosal in North-Eastern Italy during 1997–2023 and associated factors. Methods: Due to variability in patch testing and positive reactions by the centers, this study was broken down by three periods: 1997–2004 (including all centers but Trieste); 1997–2015 (considering only Padua and Pordenone); and 2010–2023 (considering only Trieste and Pordenone). Multiple logistic regression was used to investigate prevalence of sensitization to Thimerosal and associated factors. Results were expressed as adjusted odds ratio (aOR) with 95% confidence intervals (95%CI). Results: Prevalence of positive patch test reactions to Thimerosal decreased from (8.13%) in 1997 to 0.95% in 2023 across all centers combined. Prevalence of positivity to Thimerosal was 9.49% during 1997–2004 (in all centers yet excluding Trieste), 8.41% during 1997–2015 (considering only Padua and Pordenone) and 4.01% during 2010–2023 (considering only Trieste and Pordenone). A significantly decreasing trend of Thimerosal sensitization was observed during 1997–2015 (aOR = 0.94; 95%CI: 0.92; 0.95). Regardless of the study period, sensitization to Thimerosal was consistently and significantly higher among health care workers (HCWs) and in patients born during 1981–1990. Conclusions: The significantly decreasing prevalence of sensitization to Thimerosal over time likely reflected removal policies from vaccines and medications after 1999. Likewise, the higher prevalence of patch test reactions in patients born during 1981–1990 may mirror the widespread presence of this hapten in vaccines and medications in the 1980ies. Moreover, the increased prevalence of patch test reactions positive to Thimerosal in HCWs probably reflected higher influenza vaccination uptake in this group compared to other occupational categories. Positive patch test reactions to Thimerosal after 2000 were likely clinically irrelevant though. Full article

(This article belongs to the Section Epidemiology)

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26 pages, 395 KiB

Open AccessReview

Vaccination Strategies and Research Gaps in Hepatitis E Virus for Special Populations

by Meng Wang, Binwei Duan, Mengcheng Liu, Yuxuan Zhang, Feng Wu, Guangming Li and Yabo Ouyang

Vaccines 2025, 13(6), 621; https://doi.org/10.3390/vaccines13060621 - 9 Jun 2025

Abstract

Background: Hepatitis E virus (HEV) infection poses a significant health risk across diverse demographic groups, particularly among pregnant women, immunocompromised individuals, patients with chronic liver disease, and the elderly. The global epidemiology of HEV reveals distinct patterns of prevalence, transmission, and disease severity [...] Read more.

Background: Hepatitis E virus (HEV) infection poses a significant health risk across diverse demographic groups, particularly among pregnant women, immunocompromised individuals, patients with chronic liver disease, and the elderly. The global epidemiology of HEV reveals distinct patterns of prevalence, transmission, and disease severity among these populations, necessitating targeted vaccination strategies. The licensing of the Hecolin (HEV 239) vaccine offers promise, but gaps in clinical trial data and varying immune responses in high-risk groups challenge its widespread applicability. Scope: This review synthesizes data on HEV’s epidemiology, discusses the susceptibility of vulnerable populations, evaluates the efficacy and safety of HEV 239, and highlights the urgent need for clinical research tailored to these groups. Key findings underscore the complexity of vaccine response influenced by immunological, physiological, and environmental factors. Additionally, potential advancements in vaccine technology, including the development of broad-spectrum vaccines and innovative delivery systems, are discussed as future directions. Strategies: Addressing regulatory, economic, and logistical barriers remains crucial for effective HEV vaccination programs. A multidisciplinary approach integrating public health policy, rigorous clinical evaluations, and collaborative frameworks is essential to ensure equitable access to HEV vaccination, ultimately improving health outcomes on a global scale. Full article

(This article belongs to the Special Issue Hepatitis Vaccines: Safety, Efficacy and Global Impact)

21 pages, 2197 KiB

Open AccessArticle

Production and Immune Response Against Pandemic Influenza Candidate Vaccines as Preparedness Against the Circulating H5N1 Influenza Viruses

by Paulo Lee Ho, Yordanka Medina-Armenteros, Lívia Mendonça Munhoz Dati, Daniela Cajado-Carvalho, Christian Savio Silva, Pollyanna Fernandes Campos, Patrícia Antonia Estima Abreu, Júlia Tavares de Castro, Paulo Newton Tonolli, Mahyumi Fujimori, Rhubia Silveira Martins Rosa, Soledad Palameta, Michael Edward Miller, Vitor Anselmo Sakihara, Fernanda de Lima Valadares, Fabiana Lauretti Ferreira, Bianca Pereira Carvalho Holanda, Douglas Gonçalves de Macedo, Priscila Comone, Natully de Souza Suffert Fogaça, Alexandre Bimbo, Felipe Catanzaro De Moraes, Stephane Tereza Queiroz de Andrade, Helena Lage Ferreira, Edison Luiz Durigon, Clarice Weis Arns, Esper George Kallás, Milena Apetito Akamatsu and Ricardo das Neves Oliveira Show full author list Hide full author list

Vaccines 2025, 13(6), 620; https://doi.org/10.3390/vaccines13060620 - 8 Jun 2025

Abstract

Background/Objectives:H5N1 influenza viruses are spreading worldwide and threaten global public health. Preparedness is necessary to mitigate the worst-case scenario should an H5N1 influenza pandemic occur and justify the development of vaccines against circulating H5N1 viruses of concern. Methods: The production and characterization [...] Read more.

Background/Objectives:H5N1 influenza viruses are spreading worldwide and threaten global public health. Preparedness is necessary to mitigate the worst-case scenario should an H5N1 influenza pandemic occur and justify the development of vaccines against circulating H5N1 viruses of concern. Methods: The production and characterization of egg-based split and inactivated H5Nx of three distinct monovalent antigens from clades 2.3.4.4b, 2.3.2.1c, and 2.3.4 were performed at an industrial scale. These antigens were formulated and their immune responses, when combined or not with IB160 squalene-based oil-in-water emulsion adjuvant in a rat model, were evaluated in a one- or two-dose immunization schedule. IgG antibodies, hemagglutination inhibitions, and microneutralization titers were measured for vaccine-induced immunity and cross-reactivity. Results: Three monovalent vaccines from clades 2.3.4.4b, 2.3.2.1c, and 2.3.4 were produced at an industrial scale and characterized. The immune responses against the monovalent vaccines showed a clade-specific antibody response and the need to combine with IB160 adjuvant for a required immune response. Conclusions: Considering the candidate vaccine viruses (CVVs) with the testing potency reagents available and that the antibody response obtained against the CVVs produced was clade-specific, IDCDC RG-71A is the indicated CVV for the predominant currently circulating H5N1 influenza virus of clade 2.3.4.4b and must be combined with adjuvant to induce a higher and efficacious immune response in a two-dose immunization protocol. Full article

(This article belongs to the Special Issue Vaccine Development for Influenza Virus)

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15 pages, 1801 KiB

Open AccessArticle

Immunity Against Mycobacterium avium Induced by DAR-901 and BCG

by Getahun Abate, Krystal A. Meza, Chase G. Colbert, Octavio Ramos-Espinosa, Nancy J. Phillips and Christopher S. Eickhoff

Vaccines 2025, 13(6), 619; https://doi.org/10.3390/vaccines13060619 - 7 Jun 2025

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Abstract

Background: The prevalence of pulmonary nontuberculous mycobacteria (NTM) is increasing in Europe and North America. Most pulmonary NTM cases are caused by Mycobacterium avium complex (MAC). The treatment of pulmonary MAC is suboptimal with failure rates ranging from 30% to 40% and there [...] Read more.

Background: The prevalence of pulmonary nontuberculous mycobacteria (NTM) is increasing in Europe and North America. Most pulmonary NTM cases are caused by Mycobacterium avium complex (MAC). The treatment of pulmonary MAC is suboptimal with failure rates ranging from 30% to 40% and there is a need to develop new vaccines. Methods: We tested the ability of two whole-cell vaccines, DAR-901 (heat-killed M. obuense) and BCG (live-attenuated M. bovis), to induce MAC cross-reactive immunity by first immunizing BALB/c mice and then performing IFN-γ ELISPOT assays after overnight stimulation of splenocytes with live MAC. To study the ability of these vaccines to protect against MAC infection, BALB/c mice were vaccinated with DAR-901 (intradermal) or BCG (subcutaneous or intranasal) and challenged with aerosolized MAC 4 weeks later. A group of mice vaccinated with BCG were also treated with clarithromycin via gavage. Lung colony-forming units (CFU) in immunized mice and unvaccinated controls were quantified 4 weeks after infection. Histopathology was used to quantify lung inflammation and flow cytometry was used to study lung immunity in BCG-vaccinated and unvaccinated mice following MAC infection. To increase the safety profile of mucosal BCG vaccination, we studied BCG with a “kill switch” (tetR BCG) in scnn1b-transgenic mice (i.e., mice prone to cystic fibrosis-type lung diseases). Results: Our results showed that (i) DAR-901 induced cross-reactive immunity to MAC to a similar level as BCG, (ii) DAR-901 and BCG protected against aerosol MAC challenge, (iii) mucosal BCG vaccination, compared to systemic BCG and DAR-901 vaccinations, provided the best protection against MAC challenge, (iv) BCG vaccination did not interfere with anti-MAC activities of clarithromycin, (v) BCG-vaccinated mice had increased inflammation and increased frequencies of activated CD4 and CD8 T cells following MAC infection, and (vi) doxycycline treatment of tetR BCG-vaccinated mice decreased lung BCG CFU without affecting MAC immunity. Conclusions: Both DAR-901 and BCG vaccinations induce MAC cross-reactive immunity and protect against aerosolized MAC challenges. Mucosal BCG vaccination provides the best protection and TetR BCG could enhance the safety of mucosal BCG vaccination. Full article

(This article belongs to the Section Vaccines against Infectious Diseases)

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17 pages, 411 KiB

Open AccessSystematic Review

Immunity Awareness—Strategies to Improve the Degree of Acceptance of Vaccines: A Systematic Review

by Alejandro Martínez-Serrano, Montserrat Pulido-Fuentes, Blanca Notario-Pacheco, Ana María Palmar-Santos, Ana Isabel Cobo-Cuenca and Ana Díez-Fernández

Vaccines 2025, 13(6), 618; https://doi.org/10.3390/vaccines13060618 - 7 Jun 2025

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Abstract

Background/Objectives: Vaccine hesitancy is one of the top ten threats to global health. It is necessary to develop appropriate strategies to address vaccine hesitancy. This systematic review aimed to analyze strategies used to improve the acceptance of vaccines, address doubts, and/or increase confidence [...] Read more.

Background/Objectives: Vaccine hesitancy is one of the top ten threats to global health. It is necessary to develop appropriate strategies to address vaccine hesitancy. This systematic review aimed to analyze strategies used to improve the acceptance of vaccines, address doubts, and/or increase confidence and motivation in routine vaccination across all age groups. Methods: A systematic review was conducted of the MEDLINE, Dialnet, Scielo, CINAHL, and CENTRAL databases between 2018 and 2023. The inclusion criterion was full-text studies in English or Spanish that improve the degree of acceptance of vaccines and were evaluated by vaccination rate or pre- or postintervention tests. For data extraction, each study was categorized as community education, tailored messages, media, and new technologies. Results: A total of 1938 studies were identified, 38 of which were selected. New technology-based interventions used in the adult population for several vaccines offer broad reach, user interaction, and data accessibility. Tailored message strategies were used mainly among parents to foster strong relationships through respectful and empathetic dialog. Community education programs were targeted mainly at adolescents, emphasizing the use of structured, appropriate and interactive materials. Media campaigns were used as a support strategy for community education and new technology strategies due to their simplicity, wide coverage, and reach. Conclusions: The best strategies for reducing hesitancy are multicomponent interventions with structured and organized educational content based on the reasons for hesitancy and tailored to the target population. Therefore, caution must be taken when applying interventions, given that no single strategy can address this issue. Full article

(This article belongs to the Special Issue Vaccination and Public Health in the 21st Century)

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11 pages, 341 KiB

Open AccessArticle

Deficits in Long-Term Vaccine Immunity Among Childhood Cancer Survivors Despite Revaccination Programs

by Alexander Zadruzny, Eva Tiselius, Tiia Lepp, Teodora Aktas, Teghesti Tecleab, Samuel Hellman, Maja Jahnmatz and Anna Nilsson

Vaccines 2025, 13(6), 617; https://doi.org/10.3390/vaccines13060617 - 6 Jun 2025

Viewed by 152

Abstract

Background: Childhood cancer survivors (CCSs) often experience impaired humoral immunity because of cancer treatments that increase their susceptibility to vaccine-preventable diseases. This study aimed to assess the seroprevalence of tetanus and rubella antibodies in CCSs compared to healthy, age-matched controls. Additionally, we explored [...] Read more.

Background: Childhood cancer survivors (CCSs) often experience impaired humoral immunity because of cancer treatments that increase their susceptibility to vaccine-preventable diseases. This study aimed to assess the seroprevalence of tetanus and rubella antibodies in CCSs compared to healthy, age-matched controls. Additionally, we explored the impact of cancer treatments on vaccine-induced immunity, examined the extent of revaccination after treatment completion, and evaluated the effectiveness of revaccination on seroprevalence. Methods: This retrospective study included 180 CCSs previously treated at Astrid Lindgren Children’s Hospital, Stockholm, between March 2019 and January 2023. Patient data were retrieved from electronic medical records. Seroprevalence data for rubella and tetanus antibodies in the 15–19-year age group were also obtained from a national seroprevalence study conducted by the Public Health Agency of Sweden. Results: CCSs exhibited significantly lower seroprevalence for both tetanus (77.7% vs. 92.7%) and rubella (79.1% vs. 97.5%) compared to age-matched controls. Revaccination with DTP-containing vaccines was more frequently administered than with the MMR vaccine. Tetanus and rubella seroprevalence were the lowest in children who had received intense chemotherapy. Among those who were revaccinated with the DTP vaccine after intensive treatment, 81 out of 98 (82.6%) had tetanus IgG levels above the threshold, compared to 24 out of 48 (50%) unvaccinated CCSs. In contrast, among those revaccinated with MMR, 57 out of 73 (78.1%) had positive rubella IgG, compared to 53 out of 73 (72.6%) unvaccinated CCSs with rubella IgG levels above the cut-off. Conclusions: Our findings highlight that vaccines are underutilized in CCSs with a notable gap in immunity, particularly among those who have undergone intensive treatments. Unexpectedly, MMR revaccination did not significantly affect rubella immunity. Given the increasing number of CCSs, it is essential to better understand how to effectively restore vaccine immunity in this population. Full article

(This article belongs to the Section Vaccination Optimization)

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22 pages, 4591 KiB

Open AccessArticle

Immunization with Inactivated Bacillus subtilis Spores Expressing TonB-Dependent Receptor (TBDR) Protects Against Multidrug-Resistant Acinetobacter baumannii Infection

by Amalia A. Saperi, Atiqah Hazan, Nurfatihah Zulkifli, Hai-Yen Lee, Nor-Aziyah MatRahim and Sazaly AbuBakar

Vaccines 2025, 13(6), 616; https://doi.org/10.3390/vaccines13060616 - 6 Jun 2025

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Abstract

Background/Objectives: The emergence of multidrug-resistant Acinetobacter baumannii (MDR A. baumannii) as a leading cause of fatal hospital-acquired infections underscores the urgent need for effective vaccines. While oral vaccines using live Bacillus subtilis spores expressing A. baumannii TonB-dependent receptor (TBDR) show promise, biosafety [...] Read more.

Background/Objectives: The emergence of multidrug-resistant Acinetobacter baumannii (MDR A. baumannii) as a leading cause of fatal hospital-acquired infections underscores the urgent need for effective vaccines. While oral vaccines using live Bacillus subtilis spores expressing A. baumannii TonB-dependent receptor (TBDR) show promise, biosafety concerns regarding recombinant spore persistence necessitate alternative strategies. Here, we evaluated chemically inactivated B. subtilis spores displaying TBDR as a safer yet immunogenic vaccine candidate. Methods: Recombinant spores were inactivated using iron-ethanol sporicidal solution and administered to BALB/c mice (8–12 weeks old) to assess safety and immunogenicity. Toxicity was evaluated through clinical monitoring, serum biochemistry, and histopathology. Immune responses were characterized by T/B cell activation, IgG/IgA titers, and mucosal sIgA levels. Protective efficacy was determined by challenging immunized mice with MDR A. baumannii Ab35 and quantifying bacterial loads and examining tissue pathology. Results: The inactivated spores exhibited an excellent safety profile, with no adverse effects on clinical parameters, organ function, or tissue integrity. Immunization induced robust systemic and mucosal immunity, evidenced by elevated CD4+/CD8+ T cells, B cells, and antigen-specific IgG/IgA in serum and mucosal secretions. Following the challenge, vaccinated mice showed significantly reduced pulmonary bacterial burdens (>90% reduction), and preserved lung and spleen architecture compared to controls, which developed severe inflammation and tissue damage. Conclusions: These findings demonstrate that inactivated B. subtilis spores expressing TBDR are a safe, orally administrable vaccine platform that elicits protective immunity against MDR A. baumannii. By addressing biosafety concerns associated with live spores while maintaining efficacy, this approach represents a critical advance toward preventing high-risk nosocomial infections. Full article

(This article belongs to the Section Pathogens-host Immune Interface)

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21 pages, 1626 KiB

Open AccessArticle

A Comparison of Tests for Detecting Prior Exposure to Coxiella burnetii for Use with Q-VAX in Australian Human Q Fever Vaccination

by Stephen Graves, Jennifer Robson, Anja Scholzen, Richard Dzeng, Francisca Powell-Romero, Jennifer Evans, John Stenos, Meg Jeppesen, Milou L. C. E. Kouwijzer, Jordi Lankhof, Susan Raju Paul, Tatiana Proboste Ibertti, Lauren Ball, Helen Powell, Stephanie Wilkinson, Evi van Schuppen, Willemijn J. Anker-Op den Brouw, Rowland Cobbold, Anja Garritsen, Mark C. Poznansky and Ann E. Sluder Show full author list Hide full author list

Vaccines 2025, 13(6), 615; https://doi.org/10.3390/vaccines13060615 - 6 Jun 2025

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Abstract

Background/Objectives: Q-VAX vaccine, approved in Australia, prevents Q fever. However, individuals with prior Coxiella burnetii (Cb) infection have an increased risk of adverse reactions, requiring pre-vaccination screening by an intradermal hypersensitivity skin test for cell-mediated immune memory and a serological assay [...] Read more.

Background/Objectives: Q-VAX vaccine, approved in Australia, prevents Q fever. However, individuals with prior Coxiella burnetii (Cb) infection have an increased risk of adverse reactions, requiring pre-vaccination screening by an intradermal hypersensitivity skin test for cell-mediated immune memory and a serological assay for anti-Cb antibodies. The week-long interval for skin test assessment limits efficient vaccination. This study evaluated a standardized interferon-γ release assay (IGRA) as a potential skin test alternative. Methods: Immune assays were compared in Australian populations with different incidences of prior Cb exposure. Cell-mediated immunity was assessed by the Q-VAX skin test and IGRA. Serological status was evaluated with established diagnostic assays. Hypothetical vaccine eligibility decisions using combined IGRA and serology results were compared with actual clinical decisions made using current guidelines. Results: All tests performed better in detecting prior infection than in detecting prior vaccination. Only the IGRA identified all individuals with a known history of Q fever. Agreement between the skin test and IGRA was limited. Moderate agreement was observed between hypothetical vaccine eligibility determinations based on IGRA plus serology results and actual clinical decisions. IGRA-positive but serology- and skin test-negative individuals received Q-VAX without clinically significant side effects, suggesting that elevated IGRA responses alone are not predictive of susceptibility to vaccine reactogenicity. Conclusions: The IGRA is not yet a suitable skin test replacement when assessing eligibility for Q fever vaccination, despite the significant limitations of the latter. We offer recommendations for designing future studies that might allow the development of appropriate guidelines for IGRA use in vaccine eligibility screening. Full article

(This article belongs to the Section Vaccines against Infectious Diseases)

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15 pages, 5946 KiB

Open AccessArticle

Safety and Immunogenicity of a Canine Distemper DNA Vaccine Formulated with Lipid Nanoparticles in Dogs, Foxes, and Raccoon Dogs

by Hong Huo, Han Wang, Shulin Liang, Zilong Wang, Jinming Wang, Qingzhu Wang, Chan Li, Yuting Tao, Jinying Ge, Zhiyuan Wen, Jinliang Wang, Weiye Chen, Xijun Wang, Lei Shuai and Zhigao Bu

Vaccines 2025, 13(6), 614; https://doi.org/10.3390/vaccines13060614 - 6 Jun 2025

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Abstract

Background: canine distemper (CD) is a highly contagious and fatal disease caused by canine distemper virus (CDV), posing a significant threat to carnivores. New CDV strain circulation and multi-species infection may lead to the potential dilemma of safety concern and insufficient efficacy of [...] Read more.

Background: canine distemper (CD) is a highly contagious and fatal disease caused by canine distemper virus (CDV), posing a significant threat to carnivores. New CDV strain circulation and multi-species infection may lead to the potential dilemma of safety concern and insufficient efficacy of the commercial modified live vaccines. Safe and effective vaccines for canine and wildlife prevention of CD need to be continuously updated and developed. Methods: we developed two DNA vaccines, p17F-LNP and p17H-LNP, encoding the fusion protein (F) or hemagglutinin protein (H) of a field CDV strain (HLJ17) and encapsulated in lipid nanoparticles (LNPs). Serum neutralizing antibody (NAb) was evaluated via neutralization tests, and mouse serum cytokine detection were evaluated via ELISA. Results: immunization of p17F-LNP and p17H-LNP monovalent or bivalent were safe, and induced robust CDV NAb and cytokine responses in mice. LNP encapsulation improved immune responses compared to naked DNA formulation, and the bivalent formulation of p17F-LNP and p17H-LNP (p17F/H-LNP) exhibited synergistic effects with a high level of immune responses. Moreover, two doses of p17F/H-LNP induced long-lasting CDV NAb for over 300 days in dogs, and prime and boost NAb responses in foxes and raccoon dogs. Conclusions: the preliminary findings provided here warrant further development of the p17F/H-LNP vaccine for animal targets against CDV infection. Full article

(This article belongs to the Special Issue Oral and Nucleic Acid Vaccines for Zoonotic and Animal Infectious Diseases)

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5 pages, 130 KiB

Open AccessEditorial

Editors’ Introduction: Understanding and Addressing Vaccine Hesitancy

by Gary L. Kreps, Xuewei Chen and Ming Li

Vaccines 2025, 13(6), 613; https://doi.org/10.3390/vaccines13060613 - 6 Jun 2025

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Abstract

The goal of this Special Issue, “Understanding and Addressing Vaccine Hesitancy”, is to examine the current state of knowledge concerning the major causes and influences of vaccine hesitancy, as well as to suggest evidence-based solutions for the growing problem of vaccine hesitancy in [...] Read more.

The goal of this Special Issue, “Understanding and Addressing Vaccine Hesitancy”, is to examine the current state of knowledge concerning the major causes and influences of vaccine hesitancy, as well as to suggest evidence-based solutions for the growing problem of vaccine hesitancy in modern society [...] Full article

(This article belongs to the Special Issue Understanding and Addressing Vaccine Hesitancy)

17 pages, 498 KiB

Open AccessReview

Broadly Neutralizing Antibody Characteristics in Hepatitis C Virus Infection and Implications for Vaccine Design

by Nicole E. Skinner

Vaccines 2025, 13(6), 612; https://doi.org/10.3390/vaccines13060612 - 6 Jun 2025

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Abstract

Despite the use of direct-acting antiviral medications to treat hepatitis C virus (HCV), over a million people are newly infected each year, highlighting the need for a prophylactic vaccine. Due to the remarkable genetic diversity of HCV and its many immune evasion mechanisms, [...] Read more.

Despite the use of direct-acting antiviral medications to treat hepatitis C virus (HCV), over a million people are newly infected each year, highlighting the need for a prophylactic vaccine. Due to the remarkable genetic diversity of HCV and its many immune evasion mechanisms, an effective vaccine will need to elicit broadly neutralizing antibodies (bNAb). In addition to providing evidence that a prophylactic HCV vaccine is feasible, this review provides an overview of known HCV bNAb targets, common antibody sequence features associated with broad neutralization, and mechanisms of immune escape. Ongoing knowledge gaps in the field and promising future directions are also discussed. Full article

(This article belongs to the Special Issue

Vaccines and Antibody-Based Therapeutics Against Infectious Disease

)

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14 pages, 605 KiB

Open AccessArticle

Women’s Empowerment and Gender-Related Factors Associated with Maternal Tetanus Protection in 39 Low- and Middle-Income Countries

by Katherine Kirkby, Luisa Arroyave, Franciele Hellwig, M. Carolina Danovaro-Holliday, Nasir Yusuf, Shirin Heidari, Stephanie Shendale, Aluísio J. D. Barros and Ahmad Reza Hosseinpoor

Vaccines 2025, 13(6), 610; https://doi.org/10.3390/vaccines13060610 - 6 Jun 2025

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Abstract

Background: Tetanus is a vaccine-preventable disease, and therefore vaccination of women of reproductive age or during pregnancy is recommended alongside childhood tetanus vaccination. Gender-related factors related to social empowerment have been established as determinants of health service utilization; however, these social determinants have [...] Read more.

Background: Tetanus is a vaccine-preventable disease, and therefore vaccination of women of reproductive age or during pregnancy is recommended alongside childhood tetanus vaccination. Gender-related factors related to social empowerment have been established as determinants of health service utilization; however, these social determinants have not yet been explored directly with tetanus vaccination. In response, the aim of this study was to assess overall and country-specific gender-related barriers to maternal tetanus vaccine coverage. Methods: We used data from Demographic and Health Surveys (DHS) in 39 countries implemented between 2013 and 2022. Women’s empowerment was measured through three domains of the Survey-based Women’s emPowERment index (SWPER), as well as other gender-related variables. To assess the association between measures of women’s empowerment and gender-related factors and maternal tetanus immunization coverage, we used multilevel logistic models with pooled data from the 39 countries to analyze overall patterns, and we used multivariable logistic regression for each country-specific dataset to analyze country-level associations. Results: There were notable variations in the factors associated with tetanus vaccination across countries. Overall, we observed that higher levels of women’s empowerment, as measured through social independence and decision-making autonomy using the SWPER index, were associated with higher odds of maternal tetanus protection, with adjusted odds ratios of 1.23 (95%CI: 1.10–1.37) and 1.20 (95%CI: 1.02–1.40), respectively. However, women’s empowerment related to attitude to violence was not. Higher household wealth was also associated with higher odds of maternal tetanus protection overall. Conclusions: Women’s empowerment can improve the uptake of maternal tetanus vaccine. Addressing gender-related barriers may enhance vaccination coverage and contribute to the elimination of maternal and neonatal tetanus as a public health problem. However, these barriers vary from country to country, necessitating country-specific investigations to formulate tailored recommendations. Full article

(This article belongs to the Special Issue Inequality in Immunization 2025)

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18 pages, 621 KiB

Open AccessArticle

Antibody Kinetics of Immunological Memory in SARS-CoV-2-Vaccinated Healthcare Workers—The ORCHESTRA Project

by Seyedalireza Seyedi, Sara Sottile, Mahsa Abedini, Paolo Boffetta, Francesco Saverio Violante, Vittorio Lodi, Giuseppe De Palma, Emma Sala, Marcella Mauro, Francesca Rui, Stefano Porru, Gianluca Spiteri, Luigi Vimercati, Luigi De Maria, Pere Toran-Monserrat, Concepción Violán, Eleonóra Fabiánová, Jana Oravec Bérešová, Violeta Calota and Andra Neamtu

Vaccines 2025, 13(6), 611; https://doi.org/10.3390/vaccines13060611 - 5 Jun 2025

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Abstract

Background/Objectives: This study examines the longitudinal dynamics of anti-nucleocapsid (anti-N) and anti-spike (anti-S) antibody responses to SARS-CoV-2 infection and mRNA vaccination based on 81,878 serum samples from 23,616 healthcare workers (HCWs) across five European countries. It includes data across four scheduled vaccine doses—predominantly [...] Read more.

Background/Objectives: This study examines the longitudinal dynamics of anti-nucleocapsid (anti-N) and anti-spike (anti-S) antibody responses to SARS-CoV-2 infection and mRNA vaccination based on 81,878 serum samples from 23,616 healthcare workers (HCWs) across five European countries. It includes data across four scheduled vaccine doses—predominantly BNT162b2—with 25% of samples originating from individuals with confirmed prior infection, as evidenced by elevated anti-S levels, positive Anti-N antibodies, or PCR results. Methods: The study employed a shifted transformation method for data normalization and utilized the Bass diffusion model to predict antibody titer dynamics influenced by both internal factors—such as immune activation contextualized through sociodemographic issues—and external factors, including infection and vaccination. Despite the absence of direct measurements for some internal variables, the model effectively inferred their impact, enabling a rigorous and nuanced delineation of immune response profiles. Results: The Bass diffusion model rigorously captured variations in antibody titers, analyzed through demographic factors such as gender, age, and job role, while thoroughly accounting for pre-infection status. The results indicate that Anti-N antibodies, exclusively produced post-infection, exhibited a rapid decline, while anti-S antibodies, generated from both infection and vaccination, demonstrated prolonged persistence. A significant decline in anti-S levels was observed 3–5 months post-vaccination, with adaptive immunity—characterized by the dominance of internal factors effects relative to external ones—achieved in most groups after the fourth dose. However, adaptive immunity post second dose was limited to specific demographics. Conclusions: These findings emphasize the significance of the Bass Method in predicting vaccine-induced, hybrid immune responses and detecting adaptive immunity by overcoming limitations in internal factor data, thereby advancing effective vaccination and infection control strategies during public health crises. These findings highlight the Bass Method’s value in predicting vaccine-induced and hybrid immunity, effectively addressing internal factor data gaps to enhance vaccination and infection control strategies. Full article

(This article belongs to the Section COVID-19 Vaccines and Vaccination)

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23 pages, 1127 KiB

Open AccessArticle

Effects of Different Adjuvants on the Protective Efficacy of a Subcellular Vaccine Against Chlamydia abortus Infection in Sheep

by Morag Livingstone, Kevin Aitchison, Javier Palarea-Albaladejo, Sergio Gastón Caspe, Clare Underwood, Holly Hill, Cameron Cunnea, Kelly Stronach, Francesca Chianini, Gary Entrican, Sean Ranjan Wattegedera and David Longbottom

Vaccines 2025, 13(6), 609; https://doi.org/10.3390/vaccines13060609 - 5 Jun 2025

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Abstract

Background/Objective: Recently, we published three studies describing the development and optimization of a new, safe, and efficacious vaccine to protect sheep from ovine enzootic abortion, which is caused by the zoonotic pathogen Chlamydia abortus. The vaccine, which can be delivered through a [...] Read more.

Background/Objective: Recently, we published three studies describing the development and optimization of a new, safe, and efficacious vaccine to protect sheep from ovine enzootic abortion, which is caused by the zoonotic pathogen Chlamydia abortus. The vaccine, which can be delivered through a single inoculation, is based on a detergent-extracted outer membrane protein (chlamydial outer membrane complex or COMC) preparation of the pathogen. This study aimed to optimize the vaccine further by comparing the effects of different adjuvants on protective efficacy. Methods: We evaluated the effectiveness of three different vaccines (2.5 µg COMC) formulated with one of three adjuvants (Montanide ISA 70VG, Montanide ISA 61VG, and QuilA) to reduce the rate of abortion, placental load and pathology, and post-partum vaginal shedding of organisms in comparison to our benchmark 20 µg COMC/Montanide ISA 70 VG vaccine and a challenge control group of animals. The humoral and cellular immunological responses to vaccination and to challenge were also assessed. Results: The two low-dose Montanide formulated vaccines resulted in low abortion rates of 3.2 and 8.1% for ISA 70 VG and ISA 61 VG, respectively, which were comparable to the benchmark vaccine group (2.7%) and considerably lower than the QuilA (23.7%) and challenge control (36.8%) groups. Similarly, the Montanide-adjuvanted groups had much lower bacterial loads (range: 136–431 genome copies) on vaginal swabs post-parturition than the QuilA (8.9 × 10⁴ copies) and challenge control (2.4 × 10⁵ copies) groups. Conclusions: The results showed that both Montanide adjuvants are more effective for maximizing COMC vaccine efficacy than the QuilA adjuvant and result in much lower bacterial shedding of the pathogen post-parturition, which is important for minimizing potential transmission to naïve animals. Full article

(This article belongs to the Special Issue Research on Immune Response and Vaccines: 2nd Edition)

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17 pages, 836 KiB

Open AccessReview

Vaccines and Animal Models of Nipah Virus: Current Situation and Future Prospects

by Chaoxiang Lv, Jiayue He, Qiqi Zhang and Tiecheng Wang

Vaccines 2025, 13(6), 608; https://doi.org/10.3390/vaccines13060608 - 4 Jun 2025

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Abstract

Nipah virus (NiV) is a highly pathogenic paramyxovirus characterized by zoonotic infection, high mortality, and a lack of effective treatment, posing a serious threat to global public health security. Currently, it still lacks specific treatments or approved vaccines, and is listed as a [...] Read more.

Nipah virus (NiV) is a highly pathogenic paramyxovirus characterized by zoonotic infection, high mortality, and a lack of effective treatment, posing a serious threat to global public health security. Currently, it still lacks specific treatments or approved vaccines, and is listed as a potential pandemic threat pathogen by the World Health Organization. This paper systematically reviews the core progress and challenges of NiV investigation, with a focus on the development of animal models, vaccine development strategies, treatment strategy, and bottlenecks in translational medicine. Additionally, we discuss the strengths and limitations of existing animal models, including ferrets, hamsters, mice, and non-human primates (NHPs), and assess advances in vaccine platforms such as viral vectors, subunit vaccines, and mRNA-based vaccine candidates. The paper critically reviews the challenges facing translational research, conservation correlates, and outbreak preparedness, while also providing future research directions for pandemic preparedness and public health security strategies. Full article

(This article belongs to the Section Veterinary Vaccines)

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26 pages, 6162 KiB

Open AccessArticle

Ethnic Comparisons of Spike-Specific CD4+ T Cells, Serological Responses, and Neutralizing Antibody Titers Against SARS-CoV-2 Variants

by Fani Pantouli, Vanessa Silva-Moraes and Ted M. Ross

Vaccines 2025, 13(6), 607; https://doi.org/10.3390/vaccines13060607 - 4 Jun 2025

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Abstract

Background/Objectives: To evaluate how immune responses compare among ethnic groups approximately 2 years after receiving a third dose of COVID-19 vaccine (BNT162b2, mRNA-1273, ChAdOx1or BBIBP-CorV), we tested T cell responses and Spike-specific RBD-antibody titer, and neutralized antibody titer levels utilizing Spectral Flow cytometry, [...] Read more.

Background/Objectives: To evaluate how immune responses compare among ethnic groups approximately 2 years after receiving a third dose of COVID-19 vaccine (BNT162b2, mRNA-1273, ChAdOx1or BBIBP-CorV), we tested T cell responses and Spike-specific RBD-antibody titer, and neutralized antibody titer levels utilizing Spectral Flow cytometry, ELISA, and SARS-CoV-2 pseudotyped-based neutralization assays, respectively. Methods: Forty-four individuals from January–December 2023 were identified within the cohort and were classified into different ethnic backgrounds; Black (N = 13), Asian (N = 14), Caucasian (N = 17). We recognize that the “Asian” group includes diverse subpopulations with distinct genetic and environmental backgrounds, which could not be further stratified due to sample-size limitations. Spike-specific AIM+, CD4+, and CD8+ T cell responses were assessed and evaluated against SARS-CoV-2 variants, including the ancestral Wuhan, Delta, and multiple Omicron subvariants (B1.1529, BA2.86, BA.4/5, and XBB.1). Alongside we tested the RBD-IgG and neutralizing antibody titers against the ancestral Wuhan. Spearman’s correlation analysis was utilized to determine corelative relationships among the AIM+ and CD4+ T cell responses, as well as the RBD-IgG and neutralizing antibody titers. Results: Our results show robust and comparable RBD-IgG and neutralizing antibody titers across all groups, with a significant positive correlation between these two measurements. Significant differences were observed in T-cell activation, with Asian participants exhibiting lower frequencies of Spike-specific CD4+ T cells against SARS-CoV-2 Omicron subvariants and higher frequencies of cytokine-producing CD4+ T cells (TNF-α, IFN-γ, and IL-2) as compared to the Caucasian group. Breakthrough infection status was not fully controlled and may influence these findings. Conclusion: Despite a small sample size and potential confounding by natural infections within our long-time-span sampling, our data suggest persistent cellular and humoral immunity 2 years after vaccination across ethnicities, with notable differences in T cell activation and cytokine profile. These preliminary observations highlight the need for larger, more detailed studies that consider intra-ethnic diversity and hybrid immunity to better understand ethnic differences in COVID-19 vaccine responses. Full article

(This article belongs to the Special Issue 3rd Edition: Safety and Autoimmune Response to SARS-CoV-2 Vaccination)

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37 pages, 477 KiB

Open AccessReview

Recombinant Mycobacterium bovis BCG-Based HIV Vaccine: Failures and Promising Approaches for a Successful Vaccine Strategy

by Joan Joseph-Munné, Milena Maya-Hoyos, Narcís Saubi, Santiago Perez, Miguel Angel Martinez Lopez, Eder Baron and Carlos Yesid Soto

Vaccines 2025, 13(6), 606; https://doi.org/10.3390/vaccines13060606 - 3 Jun 2025

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Abstract

During 2022, AIDS claimed a life every minute and about 9.2 million HIV-infected people were not on treatment. In addition, a person living with HIV is estimated to be 20–30 times more susceptible to developing active tuberculosis. Every year, 130,000 infants are newly [...] Read more.

During 2022, AIDS claimed a life every minute and about 9.2 million HIV-infected people were not on treatment. In addition, a person living with HIV is estimated to be 20–30 times more susceptible to developing active tuberculosis. Every year, 130,000 infants are newly infected, with vertical transmission being the main cause of pediatric HIV infection. Thus, the development of an effective, safe, and accessible vaccine for neonates and/or adults is an urgent need to prevent or control HIV infection or progression to AIDS. An effective HIV vaccine should induce long-lasting mucosal immunity, broadly neutralizing antibodies, innate immunity, and robust stimulation of CD4+ and CD8+ T-cell responses. Recombinant BCG is a promising live-attenuated bacterial vaccine vector because of its capacity to stimulate T-cell immunity. As a slow-growing microorganism, it provides prolonged low-level antigenic exposure upon infecting macrophages and APCs, potentially stimulating both effector and memory T-cell responses. BCG is considered safe and is currently administered to 80% of infants in countries where it is part of the national immunization program. Additionally, BCG offers several benefits as a live vaccine vehicle since it is cost-effective, easy to mass-produce, and heat stable. It is also well-suited for newborns, as maternal antibodies do not interfere with its efficacy. Furthermore, BCG has a strong safety profile, having been administered to over three billion people as a TB vaccine. In this review, we provide an extensive summary of the literature relating to immunogenicity studies in animal models performed since 2011. Moreover, we provide a comprehensive analysis of the key factors influencing the design of recombinant BCG as a live vaccine vehicle: (i) expression vectors; (ii) selection of HIV immunogen; (iii) promoters to regulate gene expression; (iv) BCG strain and BCG codon optimization; (v) genetic plasmid stability; (vi) influence of preexisting immunity, route, and dose immunization; and (vii) safety profile. Full article

(This article belongs to the Special Issue The Development of HIV Vaccines: Advances and Challenges)

15 pages, 3706 KiB

Open AccessSystematic Review

Impact of Chemotherapy on Vaccine Immunogenicity and Revaccination Response of Acute Lymphoblastic Leukemia—A Systematic Review and Meta-Analysis

by Yuyuan Zeng, Chuanyu Yang, Xihan Li, Qi An, Bo Zhou, Wenquan Niu, Yu Tian, Yifei Cheng and Lin Wang

Vaccines 2025, 13(6), 605; https://doi.org/10.3390/vaccines13060605 - 1 Jun 2025

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Abstract

Background: Chemotherapy, a cornerstone treatment for Acute Lymphoblastic Leukemia (ALL), can compromise immune function, leading to impaired immune memory function and diminished responses to revaccination. This systematic review and meta-analysis sought to evaluate the impact of chemotherapy on the immunogenicity of prior vaccinations [...] Read more.

Background: Chemotherapy, a cornerstone treatment for Acute Lymphoblastic Leukemia (ALL), can compromise immune function, leading to impaired immune memory function and diminished responses to revaccination. This systematic review and meta-analysis sought to evaluate the impact of chemotherapy on the immunogenicity of prior vaccinations and subsequent revaccination responses in children with ALL. Methods: A comprehensive search was conducted through PubMed, Embase, Web of Science, and Medline. Search time was 9 January 2025. R 4.4.2 was employed for data analysis. Results: A total of 29 relevant studies were identified, with 8 undergoing meta-analysis. The pooled antibody seropositive rates (SPR) for vaccines against Hepatitis B Virus (HBV), Hepatitis A Virus (HAV), diphtheria, tetanus, pertussis, measles, mumps, rubella, varicella, and Pneumococcal Conjugate Vaccine (PCV) demonstrated a statistically significant decline after chemotherapy in ALL patients (p < 0.0001). Subgroup analysis further revealed marked and heterogeneous declines in SPR after chemotherapy, with the magnitude of reduction varying significantly across vaccines—tetanus, HBV, HAV, measles, mumps, and rubella (Subgroup differences, p = 0.0037). Conclusions: This review provides an updated assessment of this critical topic, representing the first meta-analysis specifically focused on the effects of chemotherapy on different vaccines’ immunogenicity in children with ALL. Full article

(This article belongs to the Special Issue Promoting Research, Development and Access to Vaccines to Address Global Inequities)

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12 pages, 221 KiB

Open AccessArticle

Development and Preclinical Evaluation of a Lyophilized Vaccine Against Equine Herpesvirus Type 4 (EHV-4)

by Lespek Kutumbetov, Balzhan Myrzakhmetova, Aiganym Tussipova, Gulzhan Zhapparova, Talshyn Tlenchiyeva, Karina Bissenbayeva, Sergazy Nurabayev and Aslan Kerimbayev

Vaccines 2025, 13(6), 604; https://doi.org/10.3390/vaccines13060604 - 31 May 2025

Viewed by 436

Abstract

Background/Objectives: Equine rhinopneumonia, caused by equine herpesvirus types 1 and 4 (EHV-1 and EHV-4), continues to be a significant health and economic concern in the global equine industry, particularly in Kazakhstan. While vaccines targeting EHV-1 are available, there is currently no licensed monovalent [...] Read more.

Background/Objectives: Equine rhinopneumonia, caused by equine herpesvirus types 1 and 4 (EHV-1 and EHV-4), continues to be a significant health and economic concern in the global equine industry, particularly in Kazakhstan. While vaccines targeting EHV-1 are available, there is currently no licensed monovalent vaccine for EHV-4, and existing formulations offer limited protection against this serotype. This study aimed to develop and evaluate a freeze-dried, live-attenuated EHV-4 vaccine with improved safety, stability, and immunogenicity. Methods: A field isolate of EHV-4 was attenuated through serial passaging in primary lamb testicle (LT-KK49) cell cultures. Viral biomass was concentrated and formulated with various stabilizers before freeze-drying. The most effective stabilizer composition—sucrose, gelatin, and lactalbumin hydrolysate—was selected based on viral titer retention. Safety and immunogenicity were assessed in mice, guinea pigs, rabbits, donkeys, and horses. A guinea pig reproductive challenge model was used to evaluate protective efficacy. Results: The optimized lyophilized vaccine retained infectivity (>6.0 log₁₀ TCID_50/cm³) for at least six months at 4 °C. No adverse clinical signs were observed in any test species. Immunization induced robust neutralizing antibody responses in both small animals and equines. In the guinea pig model, vaccinated females demonstrated 100% pregnancy retention and fetal viability following challenge with a virulent EHV-4 strain. Conclusions: This freeze-dried, live-attenuated EHV-4 vaccine candidate is safe, immunogenic, and thermostable. It offers a promising platform for the targeted prevention of EHV-4 infection, particularly in young horses and in regions with limited cold-chain infrastructure. Full article

(This article belongs to the Section Veterinary Vaccines)

16 pages, 2725 KiB

Open AccessSystematic Review

Effects of Pneumococcal Vaccination in Children Under Five Years of Age in the Democratic Republic of Congo: A Systematic Review

by Marcellin Mengouo Nimpa, Abel Ntambue, Christian Ngandu, M. Carolina Danovaro-Holliday, André Bita Fouda, Aimé Mwana-Wabene Cikomola, Jean-Crispin Mukendi, Dieudonné Mwamba, Adèle Daleke Lisi Aluma, Moise Désiré Yapi, Jean Baptiste Nikiema, Boureima Hama Sambo and Daniel Katuashi Ishoso

Vaccines 2025, 13(6), 603; https://doi.org/10.3390/vaccines13060603 - 31 May 2025

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Abstract

Background: In the Democratic Republic of Congo (DRC), the 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in 2011 through a three-dose schedule, targeting infants as part of the Expanded Program on Immunization (EPI), to reduce pneumococcal-related morbidity and mortality. The aim of this [...] Read more.

Background: In the Democratic Republic of Congo (DRC), the 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in 2011 through a three-dose schedule, targeting infants as part of the Expanded Program on Immunization (EPI), to reduce pneumococcal-related morbidity and mortality. The aim of this study was to determine the proportion of pneumonia and meningitis cases and deaths prevented in children under five following the introduction of this vaccine. Methods: This is a systematic review. We synthesized findings from studies carried out in the DRC between 2011 and 2023. We searched scientific articles, published and unpublished doctoral theses and conference proceedings. Only papers written in French or English and those reporting the results of original analytical studies were selected. We assessed the direct effect of PCV13 by calculating the proportion of infections avoided, using Odds Ratios or prevalence ratios related to infection or pneumococcal carriage. Results: Four studies were included in this review. Regarding pneumococcal carriage, when children received three PCV13 doses, the prevalence of carriage was reduced by 93.3% (95% CI: 86.3 to 96.6%), while a single dose did not significantly reduce the prevalence of carriage compared with children who had not received any dose. Concerning pneumonia prevention, three doses of PCV13 prevented 66.7% (95% CI: 37.2 to 82.2) of cases among vaccinated children. The proportion of meningitis attributable to S. pneumoniae prevented was 75.0% (95% CI: 6% to 93.3%) among children vaccinated with PCV13. S. pneumoniae serotypes 19F and 23F were the most frequent causes of invasive pneumonia in children. Serotypes 35B/35C, 15B/C, 10A and 11A/D were the most frequently identified causes of morbidity in Congolese children. In 2022, with PCV13 vaccination coverage at 79.0%, an estimated 113,359 cases of severe pneumonia and 17,255 pneumonia-related deaths were prevented in the DRC, with 3313 cases and 1544 deaths attributable to pneumococcal meningitis prevented. Conclusions: There is clear, but scattered, evidence of reduced colonization by S. pneumoniae and hospital admissions due to pneumococcal pneumonia and meningitis. The results also show that S. pneumoniae serotypes 35B/35C, 15B/C, 10A and 11A/D not included in PCV13 were the main cause of pneumococcal disease in unvaccinated or under-vaccinated children. These data support the need to continue improving vaccination coverage among children who are unvaccinated or incompletely vaccinated with PCV13 to reduce the burden of pneumococcal infections in the DRC. Full article

(This article belongs to the Special Issue Inequality in Immunization 2025)

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9 pages, 511 KiB

Open AccessBrief Report

Immunotherapeutic Blockade of CD47 Increases Virus Neutralization Antibodies

by Lamin B. Cham, Thamer A. Hamdan, Hilal Bhat, Bello Sirajo, Murtaza Ali, Khaled Saeed Tabbara, Eman Farid, Mohamed-Ridha Barbouche and Tom Adomati

Vaccines 2025, 13(6), 602; https://doi.org/10.3390/vaccines13060602 - 31 May 2025

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Abstract

Background/Objectives: CD47 is a cell surface glycoprotein moderately expressed in healthy cells and upregulated in cancer and viral infected cells. CD47’s interaction with signal regulatory protein alpha (SIRPα) inhibits phagocytic cells and its interaction with thrombospondin-1 inhibits T cell response. Experimental evidence has [...] Read more.

Background/Objectives: CD47 is a cell surface glycoprotein moderately expressed in healthy cells and upregulated in cancer and viral infected cells. CD47’s interaction with signal regulatory protein alpha (SIRPα) inhibits phagocytic cells and its interaction with thrombospondin-1 inhibits T cell response. Experimental evidence has revealed that the blockade of CD47 resulted in the increased activation and function of both innate and adaptive immune cells, therefore exerting antitumoral and antiviral effects. Recent studies have shown that the combination of vaccines and immune checkpoint inhibitors could be a promising approach to increasing vaccine immunogenicity. Here, we investigated the vaccinal effect of anti-CD47 antibodies and discussed the possibilities of combining anti-CD47 treatments with vaccines. Methods: Using vesicular stomatitis virus (VSV), a widely used replication-competent vaccine vector, we evaluated the impact of the immunotherapeutic blockade of CD47 on cellular, humoral, and protective immunity. We infected C57BL/6 mice with VSV, treated them with anti-CD47 antibodies or an isotype, and evaluated the total immunoglobulin (Ig), IgG neutralizing antibodies, B cell activation, CD8+ T cell effector function, and survival of the mice. Results: We found that the treatments of anti-CD47 antibodies led to significantly increased Ig and IgG neutralizing antibody levels compared to the isotype treatment. Flow cytometric analysis of B cells revealed no difference in the number of circulating B cells; however, we observed an increased surface expression of CD80 and CD86 in B cells among anti-CD47-treated mice. Further analysis of the impact of CD47 blockade on T immunity revealed a significantly higher percentage of IFN-γ⁺ CD4 and IFN-γ⁺ CD8 T cells in anti-CD47-treated mice. Upon infecting mice with a lethal VSV dose, we observed a significantly higher survival rate among the anti-CD47-treated mice compared to control mice. Conclusions: Our results indicate that anti-CD47 treatment induces a stronger cellular and humoral immune response, leading to better protection. As such, immunotherapy by CD47 blockade in combination with vaccines could be a promising approach to improve vaccine efficacy. Full article

(This article belongs to the Section Vaccines against Infectious Diseases)

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25 pages, 2016 KiB

Open AccessReview

mRNA Vaccine Technology Beyond COVID-19

by Sola Oloruntimehin, Florence Akinyi, Michael Paul and Olumuyiwa Ariyo

Vaccines 2025, 13(6), 601; https://doi.org/10.3390/vaccines13060601 - 31 May 2025

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Abstract

Background/Objectives: Since their approval in early 2020, mRNA vaccines have gained significant attention since the COVID-19 pandemic as a potential therapeutic approach to tackle several infectious diseases. This article aims to review the current state of mRNA vaccine technology and its use against [...] Read more.

Background/Objectives: Since their approval in early 2020, mRNA vaccines have gained significant attention since the COVID-19 pandemic as a potential therapeutic approach to tackle several infectious diseases. This article aims to review the current state of mRNA vaccine technology and its use against other diseases. Methods: To obtain accurate and reliable data, we carefully searched the clinicaltrial.gov and individual companies’ websites for current ongoing clinical trials reports. Also, we accessed different NCBI databases for recent articles or reports of clinical trials, innovative design of mRNA vaccines, and reviews. Results: Significant progress has been made in the design and improvement of mRNA vaccine technology. Currently, there are hundreds of ongoing clinical trials on mRNA vaccines against different cancer types, infectious diseases, and genetic and rare diseases, which showcase the advancement in this technology and their potential therapeutic advantages over traditional vaccine platforms. Finally, we predict what could be a potential future direction in designing more effective mRNA vaccines, particularly against cancer. Conclusions: The results of many of the ongoing clinical trials have shown significant positive outcomes, with many of the trials already at Phase III. Despite this outlook, however, some have been terminated or withdrawn for several reasons, some of which are not made available. This means that despite the advancement, there is a need for more research and critical evaluation of each innovation to better understand their immunological benefits and long-term effects. Full article

(This article belongs to the Section DNA and mRNA Vaccines)

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