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Vaccines
Volume 13
Issue 7
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Vaccines, Volume 13, Issue 7 (July 2025) – 114 articles

Cover Story (view full-size image): HIV remains a global health challenge despite significant advancements in antiretroviral therapy and prevention strategies. Developing a safe and effective vaccine that protects people worldwide has been a major goal, yet the genetic variability and rapid mutation rate of the virus continue to pose substantial challenges. Over 35 years of HIV vaccine research have yielded a mix of discouraging trial results and invaluable scientific insights that suggest an HIV vaccine will likely not resemble any traditional vaccine, as it may require novel antigen designs and delivery methods and a combination of approaches. Ongoing research remains active and continues to explore novel approaches, and these recent advances offer hope for progress in the fight against HIV. View this paper
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15 pages, 1724 KiB  
Review
Circulating Antibody’s Role During Post-Exposure Prophylaxis, and Beyond for Rabies: A Review
by Qingjun Chen, Li Cai, Xinjun Lv, Si Liu, Cheng Liu, Jiayang Liu, Xiaoqiang Liu, Wenwu Yin, Chuanlin Wang and Zhenggang Zhu
Vaccines 2025, 13(7), 775; https://doi.org/10.3390/vaccines13070775 - 21 Jul 2025
Viewed by 390
Abstract
Background: Since the introduction of Pasteur’s rabies vaccine in 1885, rabies prophylaxis and post-exposure prophylaxis (PEP) have been widely administered globally under the recommendation of the World Health Organization (WHO). However, 124 documented cases of PEP failure had been reported worldwide between 1980 [...] Read more.
Background: Since the introduction of Pasteur’s rabies vaccine in 1885, rabies prophylaxis and post-exposure prophylaxis (PEP) have been widely administered globally under the recommendation of the World Health Organization (WHO). However, 124 documented cases of PEP failure had been reported worldwide between 1980 and 2023. Additionally, sporadic media reports from China showed occasional PEP failures between 2017 and 2024. Rabies remains a serious public health problem in over 150 countries and regions. Methods: In this review, we summarize PEP procedures recommended by the Advisory Committee on Immunization Practices (ACIP) and the WHO. We also analyze potential contributing factors to PEP failure, propose a concept of circulating antibodies, and discuss their roles in PEP. Furthermore, we summarize key guidelines for clinical trial design from the U.S. Food and Drug Administration (FDA) and China’s Center for Drug Evaluation (CDE), as well as the latest developments in monoclonal antibody (cocktail) therapies. Results: Adherence to core PEP practices, such as wound cleansing, infiltration of wounds with immunoglobulin (mAbs), and administration of vaccines, and broader societal involvement are crucial for preventing rabies infection in most cases. For high-risk exposures or immunocompromised individuals, the provision of circulating antibodies through high-dose human rabies immune globulin (HRIG) or mAbs is of utmost importance for preventing PEP failure. Conclusions: Early, high-concentration circulating antibodies are important for preventing PEP failure. Addressing the global issue of rabies requires involvement of the entire society. Only through collective efforts can we tackle this neglected disease and achieve WHO’s goal of “zero by 30”. Full article
(This article belongs to the Section Vaccines and Public Health)
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18 pages, 2502 KiB  
Article
Epitope Variation in Hemagglutinin and Antibody Responses to Successive A/Victoria A(H1N1) Strains in Young and Older Adults Following Seasonal Influenza Vaccination: A Pilot Study
by Mónica Espinar-García, Isabel María Vallejo-Bermúdez, María Ángeles Onieva-García, Irene Reina-Alfonso, Luis Llapa-Chino, Pablo Álvarez-Heredia, Inmaculada Salcedo, Rafael Solana, Alejandra Pera and Alexander Batista-Duharte
Vaccines 2025, 13(7), 774; https://doi.org/10.3390/vaccines13070774 - 21 Jul 2025
Viewed by 313
Abstract
Background: Annual influenza vaccine updates target viral drift, but immune responses may be biased by original antigenic sin (OAS). Few studies have explored this across closely related strains. This study examines how OAS shapes responses to sequential influenza variants in the context of [...] Read more.
Background: Annual influenza vaccine updates target viral drift, but immune responses may be biased by original antigenic sin (OAS). Few studies have explored this across closely related strains. This study examines how OAS shapes responses to sequential influenza variants in the context of seasonal vaccination. Methods: We conducted a prospective, longitudinal study to assess the humoral immune response to the 2023–2024 seasonal influenza vaccine containing the A/Victoria/4897/2022 (H1N1) strain. Bioinformatic analyses compared the hemagglutinin (HA) sequences of A/Victoria/4897/2022 and the antigenically related A/Victoria/2570/2019 strain. B-cell epitopes were mapped with BepiPred-3.0 and BepiBlast, and their physicochemical properties analyzed via accessibility, β-turns, flexibility, and hydrophilicity. Antibody responses were measured pre- and 28 days post-Vaxigrip Tetra vaccination in young (18–35) and older (>65) adults, stratified by cytomegalovirus (CMV) serostatus. HA sequences showed >97% identity, with variations mainly in the globular head. Predicted B-cell epitopes overlapped variable sites, suggesting possible immune escape. Despite having been vaccinated against the 2022 strain, serology showed higher antibody titers against the 2019 HA strain in all participants. This pattern suggests a potential antigen imprinting effect, though confirmation awaits further analysis. Age groups differed: older adults showed greater variability, while younger CMV+ individuals tended toward stronger 2019 HA responses. Conclusions: These findings suggest a complex interplay of factors shaping immune responses, though the imprinting effect and the potential role of CMV warrant further exploration in larger, more focused studies. Full article
(This article belongs to the Special Issue Vaccine Development for Influenza Virus)
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10 pages, 480 KiB  
Review
100-Day Mission for Future Pandemic Vaccines, Viewed Through the Lens of Low- and Middle-Income Countries (LMICs)
by Yodira Guadalupe Hernandez-Ruiz, Erika Zoe Lopatynsky-Reyes, Rolando Ulloa-Gutierrez, María L. Avila-Agüero, Alfonso J. Rodriguez-Morales, Jessabelle E. Basa, Frederic W. Nikiema and Enrique Chacon-Cruz
Vaccines 2025, 13(7), 773; https://doi.org/10.3390/vaccines13070773 - 21 Jul 2025
Viewed by 430
Abstract
The 100-Day Mission, coordinated by the Coalition for Epidemic Preparedness Innovations (CEPI) and endorsed by significant international stakeholders, aims to shorten the timeframe for developing and implementing vaccines to 100 days after the report of a new pathogen. This ambitious goal is outlined [...] Read more.
The 100-Day Mission, coordinated by the Coalition for Epidemic Preparedness Innovations (CEPI) and endorsed by significant international stakeholders, aims to shorten the timeframe for developing and implementing vaccines to 100 days after the report of a new pathogen. This ambitious goal is outlined as an essential first step in improving pandemic preparedness worldwide. This review highlights the mission’s implementation potential and challenges by examining it through the lens of low- and middle-income countries (LMICs), which often face barriers to equitable vaccine access. This article explores the scientific, economic, political, and social aspects that could influence the mission’s success, relying on lessons learned from previous pandemics, such as the Spanish flu, H1N1, and COVID-19. We also examined important cornerstones like prototype vaccine libraries, accelerated clinical trial preparedness, early biomarkers identification, scalable manufacturing capabilities, and rapid pathogen characterization. The review also explores the World Health Organization (WHO) Pandemic Agreement and the significance of Phase 4 surveillance in ensuring vaccine safety. We additionally evaluate societal issues that disproportionately impact LMICs, like vaccine reluctance, health literacy gaps, and digital access limitations. Without intentional attempts to incorporate under-resourced regions into global preparedness frameworks, we argue that the 100-Day Mission carries the risk of exacerbating already-existing disparities. Ultimately, our analysis emphasizes that success will not only rely on a scientific innovation but also on sustained international collaboration, transparent governance, and equitable funding that prioritizes inclusion from the beginning. Full article
(This article belongs to the Section Vaccines and Public Health)
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21 pages, 2924 KiB  
Article
Mucosal Vaccination Against SARS-CoV-2 Using Human Probiotic Bacillus subtilis Spores as an Adjuvant Induces Potent Systemic and Mucosal Immunity
by Raul Ramos Pupo, Laura M. Reyes Diaz, Gisela M. Suarez Formigo, Yusnaby Borrego Gonzalez, Miriam Lastre Gonzalez, Danay Saavedra Hernandez, Tania Crombet Ramos, Belinda Sanchez Ramirez, Roberto Grau, Niels Hellings, Piet Stinissen, Oliver Perez and Jeroen F. J. Bogie
Vaccines 2025, 13(7), 772; https://doi.org/10.3390/vaccines13070772 - 21 Jul 2025
Viewed by 462
Abstract
Background/Objectives: The ongoing evolution of SARS-CoV-2 has highlighted the limitations of parenteral vaccines in preventing viral transmission, largely due to their failure to elicit robust mucosal immunity. Methods: Here, we evaluated an intranasal (IN) vaccine formulation consisting of recombinant receptor-binding domain [...] Read more.
Background/Objectives: The ongoing evolution of SARS-CoV-2 has highlighted the limitations of parenteral vaccines in preventing viral transmission, largely due to their failure to elicit robust mucosal immunity. Methods: Here, we evaluated an intranasal (IN) vaccine formulation consisting of recombinant receptor-binding domain (RBD) adsorbed onto human probiotic Bacillus subtilis DG101 spores. Results: In BALB/c mice, IN spore-RBD immunization induced strong systemic and mucosal humoral responses, including elevated specific IgG, IgM, and IgA levels in serum, bronchoalveolar lavage fluid (BALF), nasal-associated lymphoid tissue (NALT), and saliva. It further promoted mucosal B cell and T cell memory, along with a Th1/Tc1-skewed T cell response, characterized by increased IFN-γ-expressing CD4+ and CD8+ T cells in the lungs. Conclusions: All in all, these findings highlight the potential of intranasal vaccines adjuvanted with probiotic B. subtilis spores in inducing sterilizing immunity and limiting SARS-CoV-2 transmission. Full article
(This article belongs to the Special Issue Human Immune Responses to Infection and Vaccination)
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9 pages, 222 KiB  
Article
Evaluation of Anti-HB Levels in a Multi-Ethnic Cohort of Health Profession Students
by Lorenzo Ippoliti, Andrea Pizzo, Agostino Paolino, Luca Coppeta, Giuseppe Bizzarro, Cristiana Ferrari, Andrea Mazza, Claudia Salvi, Ersilia Buonomo, Fabian Cenko, Andrea Magrini and Antonio Pietroiusti
Vaccines 2025, 13(7), 771; https://doi.org/10.3390/vaccines13070771 - 21 Jul 2025
Viewed by 250
Abstract
Background: Despite the widespread implementation of childhood vaccination programmes, hepatitis B virus (HBV) infection remains an ongoing occupational risk for healthcare students. In multi-ethnic and international university settings, differences in vaccination programmes and immune responses must be considered. This retrospective study aimed to [...] Read more.
Background: Despite the widespread implementation of childhood vaccination programmes, hepatitis B virus (HBV) infection remains an ongoing occupational risk for healthcare students. In multi-ethnic and international university settings, differences in vaccination programmes and immune responses must be considered. This retrospective study aimed to assess the prevalence of protective levels of anti-HBs among medical students at an international university in Rome, exploring associations with demographic and vaccination-related factors. Methods: Data were collected from routine occupational health surveillance conducted in 2023. Anti-HB titres were measured in 507 students, and information on age, sex, country of birth, age at vaccination, and time since the last dose was analysed. Results: Overall, 55.0% of students had antibody levels of at least 10 mIU/mL, indicating serological protection. Higher seroprotection rates were observed among students vaccinated in the first year of life compared to those vaccinated later. A significant decline in antibody titres was also associated with longer intervals since vaccination. Students born outside Europe tended to show lower levels of protection. Conclusions: These results emphasise the importance of screening future healthcare professionals and continuously monitoring antibody titres to help reduce HBV infections. Full article
(This article belongs to the Section Hepatitis Virus Vaccines)
12 pages, 475 KiB  
Review
Meningococcal B Vaccines as a Paradigm of Safe and Effective Vaccines for Children
by Maribel Gonzalez Tome, Rosa Gonzalez-Quevedo, Maria Escudeiro dos Santos, Hans Juergen Dornbusch, Sabine Straus and Emer Cooke
Vaccines 2025, 13(7), 770; https://doi.org/10.3390/vaccines13070770 - 21 Jul 2025
Viewed by 408
Abstract
Background: Neisseria meningitidis B is one of the main causative pathogens of meningitis and other forms of severe meningococcal disease. In the past decade, meningococcal B vaccines have been developed to address this infection and its sequelae. Objective: This article aims to present [...] Read more.
Background: Neisseria meningitidis B is one of the main causative pathogens of meningitis and other forms of severe meningococcal disease. In the past decade, meningococcal B vaccines have been developed to address this infection and its sequelae. Objective: This article aims to present an example of how the EU regulatory framework allowed the early authorisation of two life-saving vaccines initially based on immunogenicity surrogates of clinical evidence. This was subsequently followed by post-marketing surveillance providing real-world evidence to support their safety profile and impact on the paediatric population in the EU. Methods: We review the evidence supporting the initial regulatory approval of the vaccines, the confirmatory data demonstrating vaccine effectiveness post-authorisation, and the real-world impact of these vaccines on the paediatric population. Results: Two vaccines were approved in the EU for active immunisation to prevent IMD caused by MenB (4CMenB in 2013 and MenB-fHBP in 2017). Both marketing authorisations were based on immunogenicity data (efficacy studies were not feasible due to the rarity of the disease) and safety data generated from pre-authorisation studies. Additional pharmacovigilance activities to further investigate the safety profile and effectiveness studies were requested to be conducted after approval. Both the effectiveness and safety profile of the vaccines were confirmed by these data. Conclusions: This paper illustrates that the EU medicines regulatory framework and safety monitoring system are robust. By supplementing the initial evidence with post-authorisation studies, further effectiveness and safety data enabled regulators to confirm the positive benefit–risk of the vaccines without delaying their access to the people who need them. Full article
(This article belongs to the Special Issue Vaccination and Public Health in the 21st Century)
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12 pages, 396 KiB  
Review
Insect-Specific Flaviviruses Have Potential Applications as a Scaffold for Pathogenic Flavivirus Vaccines
by Jia-Zhen Cui, Xiang-Hua Xiong, Qing-Yang Wang, Hao-Long Dong, Gang Liu and Hui-Peng Chen
Vaccines 2025, 13(7), 769; https://doi.org/10.3390/vaccines13070769 - 21 Jul 2025
Viewed by 315
Abstract
Pathogenic flaviviruses are predominantly the pathogens of emerging and re-emerging infectious diseases, which have caused multiple public health emergencies globally and pose a serious threat to human health and social development. Although significant achievements have been made in vaccine research, issues such as [...] Read more.
Pathogenic flaviviruses are predominantly the pathogens of emerging and re-emerging infectious diseases, which have caused multiple public health emergencies globally and pose a serious threat to human health and social development. Although significant achievements have been made in vaccine research, issues such as limited protective effects and virulence reversion persist, making the development of novel vaccines against pathogenic flaviviruses a current research hotspot and challenge. ISFVs have recently attracted attention due to their high homology with pathogenic flaviviruses and unique inability to replicate in mammalian hosts. Multiple vaccine candidate strains constructed using ISFVs as scaffolds have demonstrated excellent safety and efficacy. This review summarizes the biological characteristics, host restriction factors, current applications in vaccine development, and challenges faced by ISFVs, providing a reference for future research on pathogenic flavivirus vaccines. Full article
(This article belongs to the Special Issue Vaccines Against Flaviviruses and Alphaviruses: Recent Advances and Future Challenges—2nd Edition)
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23 pages, 1372 KiB  
Article
Immunization with Complete Freund’s Adjuvant Reveals Trained Immunity-like Features in A/J Mice
by Kiruthiga Mone, Shraddha Singh, Fatema Abdullatif, Meghna Sur, Mahima T. Rasquinha, Javier Seravalli, Denise K. Zinniel, Indranil Mukhopadhyay, Raul G. Barletta, Teklab Gebregiworgis and Jay Reddy
Vaccines 2025, 13(7), 768; https://doi.org/10.3390/vaccines13070768 - 21 Jul 2025
Viewed by 508
Abstract
Background/Objectives: Freund’s adjuvants induce different immunomodulatory effects, but their underlying molecular mechanisms are unclear. In this study, we investigated whether the immune-stimulating effects of the complete Freund’s adjuvant (CFA) involve the mechanisms of trained immunity (TI). Methods: We examined bone marrow cells (BMCs) [...] Read more.
Background/Objectives: Freund’s adjuvants induce different immunomodulatory effects, but their underlying molecular mechanisms are unclear. In this study, we investigated whether the immune-stimulating effects of the complete Freund’s adjuvant (CFA) involve the mechanisms of trained immunity (TI). Methods: We examined bone marrow cells (BMCs) isolated from CFA-immunized A/J mice to address this question. Incomplete Freund’s adjuvant (IFA) and Mycobacterium tuberculosis var. bovis Bacillus Calmette-Guérin (BCG) served as negative and positive controls, respectively. We evaluated cytokine profiles, metabolic, and epigenetic changes. Results: First, BMCs from all groups except saline showed varied levels of IL-1β, IL-6, and TNF-α. But expression of CCL5 and CXCL10 was significantly elevated only in the CFA and BCG groups. Transcriptionally, significant elevations were noted for TNF-α and IL-1β in the CFA and BCG groups, whereas CXCL10, IL-6, and IL-10 were upregulated in the CFA and BCG groups, respectively. Second, while BMCs from the BCG group expressed the markers of both the M1 and M2 macrophages, no clear trends were noted in the CFA and IFA groups. Third, cell lysates from the CFA group revealed metabolic reprogramming in the BMCs. Specifically, we observed an increased level of lactate, indicative of aerobic glycolysis, which is implicated in TI, and this was also detected in the IFA group. Fourth, epigenetic analysis revealed histone enrichment in the promoter region of TNF-α, in the CFA group, but to a lesser degree than the BCG group. However, no epigenetic changes were observed in the IFA group. Conclusions: Our data provide new insights into the mechanisms of Freund’s adjuvants and the immunomodulatory effects of CFA could involve the features of TI. Full article
(This article belongs to the Special Issue Recent Advances in Vaccine Adjuvants and Formulation)
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67 pages, 4242 KiB  
Review
Bioengineering Outer-Membrane Vesicles for Vaccine Development: Strategies, Advances, and Perspectives
by Ayesha Zahid, Hazrat Ismail, Jennifer C. Wilson and I. Darren Grice
Vaccines 2025, 13(7), 767; https://doi.org/10.3390/vaccines13070767 - 20 Jul 2025
Viewed by 734
Abstract
Outer-membrane vesicles (OMVs), naturally secreted by Gram-negative bacteria, have gained recognition as a versatile platform for the development of next-generation vaccines. OMVs are essential contributors to bacterial pathogenesis, horizontal gene transfer, cellular communication, the maintenance of bacterial fitness, and quorum sensing. Their intrinsic [...] Read more.
Outer-membrane vesicles (OMVs), naturally secreted by Gram-negative bacteria, have gained recognition as a versatile platform for the development of next-generation vaccines. OMVs are essential contributors to bacterial pathogenesis, horizontal gene transfer, cellular communication, the maintenance of bacterial fitness, and quorum sensing. Their intrinsic immunogenicity, adjuvant properties, and scalability establish OMVs as potent tools for combating infectious diseases and cancer. Recent advancements in genetic engineering and biotechnology have further expanded the utility of OMVs, enabling the incorporation of multiple epitopes and antigens from diverse pathogens. These developments address critical challenges such as antigenic variability and co-infections, offering broader immune coverage and cost-effective solutions. This review explores the unique structural and immunological properties of OMVs, emphasizing their capacity to elicit robust immune responses. It critically examines established and emerging engineering strategies, including the genetic engineering of surface-displayed antigens, surface conjugation, glycoengineering, nanoparticle-based OMV engineering, hybrid OMVs, and in situ OMV production, among others. Furthermore, recent advancements in preclinical research on OMV-based vaccines, including synthetic OMVs, OMV-based nanorobots, and nanodiscs, as well as emerging isolation and purification methods, are discussed. Lastly, future directions are proposed, highlighting the potential integration of synthetic biology techniques to accelerate research on OMV engineering. Full article
(This article belongs to the Special Issue Bioengineering Strategies for Developing Vaccines)
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12 pages, 574 KiB  
Article
Vaccination in Aged Care in Australia: A Retrospective Study of Influenza, Herpes Zoster, and Pneumococcal Vaccination
by Stephen Wiblin, Yuen Lai, Natalie Soulsby and Jodie Hillen
Vaccines 2025, 13(7), 766; https://doi.org/10.3390/vaccines13070766 - 20 Jul 2025
Viewed by 245
Abstract
Background: Older adults living in aged care are at risk of poor health outcomes due to influenza, pneumococcal disease, and herpes zoster infections. Despite these conditions being vaccine-preventable, little is known about vaccine uptake rates in the residential elderly care setting in [...] Read more.
Background: Older adults living in aged care are at risk of poor health outcomes due to influenza, pneumococcal disease, and herpes zoster infections. Despite these conditions being vaccine-preventable, little is known about vaccine uptake rates in the residential elderly care setting in Australia. Methods: This was a retrospective cohort study examining the medical records of residents of 31 aged care homes in Australia (n = 1108). Data were extracted from medical records for the period March 2023 to September 2023. The proportion of residents vaccinated against influenza, pneumococcal disease, and herpes zoster was calculated. Univariate and multivariate logistic regressions were used to identify possible demographic and other characteristics associated with the vaccination uptake. Results: This study included 1108 residents. Two-thirds (68%) were female, and the median age was 87 years. All residents had one or more comorbidities. Most (92.6%) had received an influenza vaccine within the prior two years, but only 38.3% had received a pneumococcal vaccine, and 16.8% had received herpes zoster vaccination. In all models, receipt of the other vaccines was a significant predictor for vaccine administration. The other factor associated with influenza vaccination was non-consumption of alcohol and younger age for herpes zoster vaccination. Conclusions: While there is a high uptake of influenza vaccines, there is a low uptake of both pneumococcal and herpes zoster vaccines in residents of aged care facilities. Further research into the barriers and enablers of vaccine uptake should be undertaken, with the goal of increasing the vaccination uptake in this vulnerable population. Full article
(This article belongs to the Section Vaccines and Public Health)
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18 pages, 994 KiB  
Article
Optimizing PBMC Cryopreservation and Utilization for ImmunoSpot® Analysis of Antigen-Specific Memory B Cells
by Noémi Becza, Lingling Yao, Paul V. Lehmann and Greg A. Kirchenbaum
Vaccines 2025, 13(7), 765; https://doi.org/10.3390/vaccines13070765 - 19 Jul 2025
Viewed by 401
Abstract
Background: Measuring frequencies of antigen-specific memory B cells (Bmem), their immunoglobulin (Ig) class and subclass usage, cross-reactivity, and affinity can provide insights into the efficacy of future antibody responses in case of antigen re-encounter. B cell ImmunoSpot® assays can provide [...] Read more.
Background: Measuring frequencies of antigen-specific memory B cells (Bmem), their immunoglobulin (Ig) class and subclass usage, cross-reactivity, and affinity can provide insights into the efficacy of future antibody responses in case of antigen re-encounter. B cell ImmunoSpot® assays can provide such information; however, like most cell-based tests, they require considerable amounts of blood to be drawn from the donor and this has hindered their inclusion in clinical trials and routine immune diagnostics. Methods: We introduce strategies for reducing the cell numbers required to 2–3 million peripheral blood mononuclear cells (PBMCs) per antigen, obtainable from 2–3 mL of blood from healthy adult donors. Results: Except when Bmem frequencies were very low, we found that testing PBMCs in singlet wells, but in serial dilution, enables as reliable Bmem frequency assessments as when testing replicate wells at a single fixed cell number. Additionally, B cell ImmunoSpot® assays can be multiplexed for detecting four Ig classes, or IgG subclasses, simultaneously and without loss of sensitivity. The requirement for low cell numbers and the retention of B cell functionality by cryopreserved PBMCs equivalent to freshly isolated material implies that fewer than the standard 10 million PBMCs per vial can be frozen. This would reduce the number of individuals who could not be tested for Bmem due to insufficient availability of PBMCs, a common problem with such assays. Conclusions: The predictable need for and recovery of cryopreserved PBMCs facilitates planning of and optimal cell utilization in B cell ImmunoSpot® assays and increases the practical feasibility of extensive Bmem characterization in larger cohorts. Full article
(This article belongs to the Special Issue Vaccination-Induced Antibody and B Cell Immune Response)
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12 pages, 1656 KiB  
Article
mRNA-LNP Vaccines Targeting SmpA-PLD and OmpK-Omp22 Induce Protective Immunity Against Acinetobacter baumannii
by Cong Liu, Xingyun Wang, Yueling Zheng, Xingyue Gao, Jiahui Jin, Xing Cheng, Yunjiao He and Peng George Wang
Vaccines 2025, 13(7), 764; https://doi.org/10.3390/vaccines13070764 - 19 Jul 2025
Viewed by 411
Abstract
Background: Acinetobacter baumannii (A. baumannii) has emerged as a critical human pathogen, causing high mortality rates among hospitalized patients and frequently triggering nosocomial outbreaks. The increasing prevalence of multidrug-resistant (MDR) A. baumannii poses a pressing threat to public health. To date, [...] Read more.
Background: Acinetobacter baumannii (A. baumannii) has emerged as a critical human pathogen, causing high mortality rates among hospitalized patients and frequently triggering nosocomial outbreaks. The increasing prevalence of multidrug-resistant (MDR) A. baumannii poses a pressing threat to public health. To date, no commercially available vaccine against A. baumannii has been developed for clinical use. messenger RNA (mRNA)–lipid nanoparticle (LNP) vaccines have emerged as a promising vaccination strategy. Methods: In this work, we developed two mRNA vaccines targeting SmpA-PLD and the fusion protein of outer membrane proteins OmpK and Omp22. The mRNA was encapsulated in LNP and administered to BALB/c mice. We evaluated humoral and cellular immune responses, bacterial burden, inflammation, and protective efficacy against A. baumannii infection in a sepsis model. Results: These mRNA vaccines triggered robust humoral and cellular immune responses in BALB/c mice, reduced bacterial burden and inflammation in sepsis models, and provided significant protection against A. baumannii infection. Notably, the OmpK-Omp22 vaccine exhibited superior protective efficacy, reducing bacterial loads in various organs and improving survival rates in the sepsis model compared to the SmpA-PLD vaccine. Conclusions: Our findings demonstrate mRNA-LNP vaccine technology as a versatile and promising platform for the development of innovative therapeutics against A. baumannii, with the potential to mitigate acute disease and promote bacterial decolonization. These findings pave the way for the development of urgently needed and effective antibacterial vaccines. Full article
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16 pages, 881 KiB  
Article
Evaluating Free PPV23 Vaccination for the Elderly in Nanning, China: A Cost-Effectiveness Analysis
by Zhengqin Su, Linlin Deng, Dan Luo, Jianying Ren, Xiaozhen Shen, Wenjie Liang, Haibin Wei, Xiong Zou, Zhongyou Li and Hai Li
Vaccines 2025, 13(7), 763; https://doi.org/10.3390/vaccines13070763 - 18 Jul 2025
Viewed by 361
Abstract
Background: This study aims to evaluate the cost-effectiveness of providing the 23-valent pneumococcal polysaccharide vaccine (PPV23) free of charge versus self-paying vaccination among adults aged 60 years and older in Nanning, Guangxi, China. Methods: A decision tree–Markov model was developed to [...] Read more.
Background: This study aims to evaluate the cost-effectiveness of providing the 23-valent pneumococcal polysaccharide vaccine (PPV23) free of charge versus self-paying vaccination among adults aged 60 years and older in Nanning, Guangxi, China. Methods: A decision tree–Markov model was developed to compare three strategies (government-funded free vaccination, self-funded vaccination, and no vaccination) over a 5-year time horizon. The model incorporated local epidemiological data and cost parameters, applying a 3% discount rate. Sensitivity analyses were conducted on key parameters, including vaccine effectiveness against pneumonia and pneumonia treatment costs. Results: The benefit–cost ratios for free and self-funded vaccination were 0.075 and 0.015, respectively, both below the cost-effectiveness threshold of 1. However, the free vaccination strategy resulted in a higher net benefit (USD 399,651.32) compared to the self-funded strategy (USD 222,594.14), along with a lower Incremental Cost-Effectiveness Ratio (ICER) (USD 1.47 per USD 0.14 of avoided disease cost). Although both strategies yielded benefit–cost ratios far below the conventional threshold of 1, the free strategy demonstrated relatively greater economic efficiency. Sensitivity analyses confirmed that vaccine effectiveness against pneumonia and treatment costs were key drivers of economic outcomes. Conclusions: While neither vaccination strategy achieved conventional cost-effectiveness benchmarks in this setting, the free PPV23 vaccination program demonstrated relatively greater economic efficiency compared to the self-funded approach; although neither strategy met the conventional cost-effectiveness thresholds, they should be considered for inclusion in regional health policy for older adults. Full article
(This article belongs to the Section Vaccines and Public Health)
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27 pages, 2739 KiB  
Article
Immunogenicity of DNA, mRNA and Subunit Vaccines Against Beak and Feather Disease Virus
by Buyani Ndlovu, Albertha R. van Zyl, Dirk Verwoerd, Edward P. Rybicki and Inga I. Hitzeroth
Vaccines 2025, 13(7), 762; https://doi.org/10.3390/vaccines13070762 - 17 Jul 2025
Viewed by 573
Abstract
Background/Objectives: Beak and feather disease virus (BFDV) is the causative agent of psittacine beak and feather disease (PBFD), affecting psittacine birds. There is currently no commercial vaccine or treatment for this disease. This study developed a novel BFDV coat protein mRNA vaccine encapsidated [...] Read more.
Background/Objectives: Beak and feather disease virus (BFDV) is the causative agent of psittacine beak and feather disease (PBFD), affecting psittacine birds. There is currently no commercial vaccine or treatment for this disease. This study developed a novel BFDV coat protein mRNA vaccine encapsidated by TMV coat protein to form pseudovirions (PsVs) and tested its immunogenicity alongside BFDV coat protein (CP) subunit and DNA vaccine candidates. Methods: mRNA and BFDV CP subunit vaccine candidates were produced in Nicotiana benthamiana and subsequently purified using PEG precipitation and gradient ultracentrifugation, respectively. The DNA vaccine candidate was produced in E. coli cells harbouring a plasmid with a BFDV1.1mer pseudogenome. Immunogenicity of the vaccine candidates was evaluated in African grey parrot chicks. Results: Successful purification of TMV PsVs harbouring the mRNA vaccine, and of the BFDV-CP subunit vaccine, was confirmed by SDS-PAGE and western blot analysis. TEM analyses confirmed formation of TMV PsVs, while RT-PCR and RT-qPCR cDNA amplification confirmed encapsidation of the mRNA vaccine candidate within TMV particles. Restriction digests verified presence of the BFDV1.1mer genome in the plasmid. Four groups of 5 ten-week-old African grey parrot (Psittacus erithacus) chicks were vaccinated and received two boost vaccinations 2 weeks apart. Blood samples were collected from all four groups on day 14, 28 and 42, and sera were analysed using indirect ELISA, which showed that all vaccine candidates successfully elicited specific anti-BFDV-CP immune responses. The subunit vaccine candidate showed the strongest immune response, indicated by higher binding titres (>6400), followed by the mRNA and DNA vaccine candidates. Conclusions: The candidate vaccines present an important milestone in the search for a protective vaccine against PBFD, and their inexpensive manufacture could considerably aid commercial vaccine development. Full article
(This article belongs to the Special Issue Innovations in Vaccine Technology)
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22 pages, 680 KiB  
Review
Adaptation of the Vaccine Prophylaxis Strategy to Variants of the SARS-CoV-2 Virus
by Sofia M. Gulova, Uliana S. Veselkina and Irina V. Astrakhantseva
Vaccines 2025, 13(7), 761; https://doi.org/10.3390/vaccines13070761 - 17 Jul 2025
Viewed by 542
Abstract
The emergence of a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus closely related to SARS-CoV and officially known as Betacoronavirus pandemicum precipitated a substantial surge in vaccine development that culminated during the global COVID-19 pandemic. At present, there are dozens of [...] Read more.
The emergence of a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus closely related to SARS-CoV and officially known as Betacoronavirus pandemicum precipitated a substantial surge in vaccine development that culminated during the global COVID-19 pandemic. At present, there are dozens of vaccines for the prevention of SARS-CoV-2 being utilized across the globe. However, only 10 of these vaccines have been authorized by the World Health Organization (WHO). These include mRNA-based, viral vector, subunit and whole-virion inactivated vaccines. At the current end of the pandemic, there has been a decline in the global vaccination rate, both for the general population and for those most at risk of severe illness from the virus. This suggests that the effectiveness of the vaccines may be waning. The decline occurs alongside a decrease in testing and sequencing for SARS-CoV-2. Furthermore, the process of tracking viruses becomes increasingly complex, thereby providing a selective advantage for SARS-CoV-2 and allowing it to evolve stealthily. In this review, we provide a comprehensive overview of viral evolution and vaccine development. We also discuss ways to overcome viral variability and test universal vaccines for all SARS-CoV-2 variants. Full article
(This article belongs to the Special Issue COVID Vaccines: Design, Development, and Immune Response Studies: 2nd Edition)
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6 pages, 411 KiB  
Brief Report
Neutralization Activity of Standard and Hyperimmune Intravenous Immunoglobulins Against Recently Circulating SARS-CoV-2 Variants
by Dongxiao Liu, Lorenza Bellusci, Hana Golding and Surender Khurana
Vaccines 2025, 13(7), 760; https://doi.org/10.3390/vaccines13070760 - 17 Jul 2025
Viewed by 322
Abstract
Our study demonstrates that IVIG lots manufactured in 2023–2024 contain neutralizing antibodies against circulating Omicron variants, including KP.3 and XEC. These variants are resistant to all convalescent plasma and IVIG preparations produced prior to 2023. Therefore, recent IVIG lots may provide some protection [...] Read more.
Our study demonstrates that IVIG lots manufactured in 2023–2024 contain neutralizing antibodies against circulating Omicron variants, including KP.3 and XEC. These variants are resistant to all convalescent plasma and IVIG preparations produced prior to 2023. Therefore, recent IVIG lots may provide some protection against COVID-19 caused by circulating SARS-CoV-2 variants. Full article
(This article belongs to the Section COVID-19 Vaccines and Vaccination)
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11 pages, 1020 KiB  
Communication
XBB.1.5 COVID-19 mRNA Vaccines Induce Inadequate Mucosal Immunity in Patients with Inflammatory Bowel Disease
by Simon Woelfel, Joel Dütschler, Daniel Junker, Marius König, Georg Leinenkugel, Claudia Krieger, Samuel Truniger, Annett Franke, Seraina Koller, Katline Metzger-Peter, Nicola Frei, STAR SIGN Study Investigators, Werner C. Albrich, Matthias Friedrich, Jan Hendrik Niess, Nicole Schneiderhan-Marra, Alex Dulovic, Wolfgang Korte, Justus J. Bürgi and Stephan Brand
Vaccines 2025, 13(7), 759; https://doi.org/10.3390/vaccines13070759 - 16 Jul 2025
Viewed by 446
Abstract
Background: Mucosal immunity plays a pivotal role in preventing infections with SARS-CoV-2. While COVID-19 mRNA vaccines induce robust systemic immune responses in patients with inflammatory bowel disease (IBD), little is known about their efficacy in the mucosal immune compartment. In this sub-investigation of [...] Read more.
Background: Mucosal immunity plays a pivotal role in preventing infections with SARS-CoV-2. While COVID-19 mRNA vaccines induce robust systemic immune responses in patients with inflammatory bowel disease (IBD), little is known about their efficacy in the mucosal immune compartment. In this sub-investigation of the ongoing STAR-SIGN study, we present the first analysis of mucosal immunity elicited by XBB.1.5 mRNA vaccines in immunocompromised patients with IBD. Methods: IgG and IgA antibodies targeting the receptor-binding domain of the SARS-CoV-2 JN.1 variant were quantified longitudinally in the saliva of IBD patients using the multiplex immunoassay MultiCoV-Ab. Antibody levels were quantified before and 2–4 weeks after vaccination with XBB.1.5 mRNA vaccines. All patients previously received three doses with original COVID-19 vaccines. Results: Mucosal IgG antibodies were readily induced by XBB.1.5 mRNA vaccines (p = 0.0013 comparing pre- and post-vaccination levels). However, mucosal IgA levels were comparable before and after vaccination (p = 0.8233). Consequently, mucosal IgG and IgA antibody levels correlated only moderately before and after immunization (pre-vaccination: r = 0.5294; p = 0.0239; post-vaccination: r = 0.4863; p = 0.0407). Contrary to a previous report in healthy individuals, vaccination did not induce serum IgA in patients with IBD (p = 0.5841 comparing pre- and post-vaccination levels). These data suggest that COVID-19 mRNA vaccines fail to elicit mucosal IgA in patients with IBD. Conclusions: Since mucosal IgA plays a pivotal role in infection control, the lack of IgA induction indicates that patients lack sufficient protection against SARS-CoV-2 infections which warrants the development of mucosal COVID-19 vaccines. Full article
(This article belongs to the Special Issue Vaccine Efficacy and Safety in Patients with Immune-Mediated Intestinal Diseases)
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13 pages, 3597 KiB  
Article
Effects of Canine IL-12 on the Immune Response Against the Canine Parvovirus VP2 Protein
by Shiyan Wang, Wenjie Jiao, Dannan Zhao, Yuzhu Gong, Jingying Ni, Huawei Wu, Jige Du, Tuanjie Wang and Chunsheng Yin
Vaccines 2025, 13(7), 758; https://doi.org/10.3390/vaccines13070758 - 16 Jul 2025
Viewed by 332
Abstract
Background: Canine parvovirus (CPV) is a highly pathogenic virus that predominantly affects puppies, with mortality rates exceeding 70%. Although commercial multivalent live attenuated vaccines (MLV) are widely employed, their efficacy is often compromised by maternal antibody interference. Consequently, the development of novel vaccines [...] Read more.
Background: Canine parvovirus (CPV) is a highly pathogenic virus that predominantly affects puppies, with mortality rates exceeding 70%. Although commercial multivalent live attenuated vaccines (MLV) are widely employed, their efficacy is often compromised by maternal antibody interference. Consequently, the development of novel vaccines remains imperative for effective CPV control. Methods: Recombinant CPV VP2 protein (rVP2) and canine interlukine 12 protein (rcIL-12) were expressed using the Bac-to-Bac baculovirus expression system and the biological activity of these proteins was assessed through hemagglutination, Cell Counting Kit-8 (CCK8) and IFN-γ induction assays. The combined immunoenhancement effect of rVP2 and rcIL-12 protein was evaluated in puppies. Results: Both rVP2 and rcIL-12 were successfully expressed and purified, exhibiting confirmed antigenicity, immunogenicity, and bioactivity. Co-administration of rVP2 with rcIL-12 elicited higher neutralizing antibody titer (6–7 times higher), complete challenge protection efficiency (no clinical symptoms and tissue and organ lesions), fewer viral shedding (decreasing significantly 8-day post challenge) and superior viral blockade (lower viral load in the organism) compared to rVP2 alone. Conclusions: Our findings demonstrate that rVP2 co-administered with rcIL-12 induces robust protective immunity in puppies and significantly mitigated the inhibitory effects of maternal antibodies. This represents a promising strategy for enabling earlier vaccination in puppies and rational design of CPV subunit vaccines. Full article
(This article belongs to the Section Veterinary Vaccines)
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26 pages, 3044 KiB  
Article
Optimization of YF17D-Vectored Zika Vaccine Production by Employing Small-Molecule Viral Sensitizers to Enhance Yields
by Sven Göbel, Tilia Zinnecker, Ingo Jordan, Volker Sandig, Andrea Vervoort, Jondavid de Jong, Jean-Simon Diallo, Peter Satzer, Manfred Satzer, Kai Dallmeier, Udo Reichl and Yvonne Genzel
Vaccines 2025, 13(7), 757; https://doi.org/10.3390/vaccines13070757 - 16 Jul 2025
Viewed by 786
Abstract
Background: Modern viral vector production needs to consider process intensification for higher yields from smaller production volumes. However, innate antiviral immunity triggered in the producer cell may limit virus replication. While commonly used cell lines (e.g., Vero or E1A-immortalised cells) are already compromised [...] Read more.
Background: Modern viral vector production needs to consider process intensification for higher yields from smaller production volumes. However, innate antiviral immunity triggered in the producer cell may limit virus replication. While commonly used cell lines (e.g., Vero or E1A-immortalised cells) are already compromised in antiviral pathways, the redundancy of innate signaling complicates host cell optimization by genetic engineering. Small molecules that are hypothesized to target antiviral pathways (Viral Sensitizers, VSEs) added to the culture media offer a versatile alternative to genetic modifications to increase permissiveness and, thus, viral yields across multiple cell lines. Methods: To explore how the yield for a chimeric Zika vaccine candidate (YF-ZIK) could be further be increased in an intensified bioprocess, we used spin tubes or an Ambr15 high-throughput microbioreactor system as scale-down models to optimize the dosing for eight VSEs in three host cell lines (AGE1.CR.pIX, BHK-21, and HEK293-F) based on their tolerability. Results: Addition of VSEs to an already optimized infection process significantly increased infectious titers by up to sevenfold for all three cell lines tested. The development of multi-component VSE formulations using a design of experiments approach allowed further synergistic titer increases in AGE1.CR.pIX cells. Scale-up to 1 L stirred-tank bioreactors and 3D-printed mimics of 200 or 2000 L reactors resulted in up to threefold and eightfold increases, respectively. Conclusions: Addition of single VSEs or combinations thereof allowed a further increase in YF-ZIK titers beyond the yield of an already optimized, highly intensified process. The described approach validates the use of VSEs and can be instructive for optimizing other virus production processes. Full article
(This article belongs to the Special Issue Vaccines Against Flaviviruses and Alphaviruses: Recent Advances and Future Challenges—2nd Edition)
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11 pages, 207 KiB  
Article
A Cross-Sectional Survey to Identify Current Pneumococcal Vaccination Practices and Barriers in Rural Community Pharmacies
by Ashley H. Chinchilla, Tyler C. Melton, Salisa C. Westrick, Tessa J. Hastings, Leticia Vieira, Grace T. Marley and Delesha M. Carpenter
Vaccines 2025, 13(7), 756; https://doi.org/10.3390/vaccines13070756 - 16 Jul 2025
Viewed by 352
Abstract
Background: Pneumococcal vaccination rates in the United States (US) remain suboptimal, especially for adults aged 19 to 64 with high-risk medical conditions. Community-pharmacy-based immunization services increase vaccine access, particularly in rural areas. This study describes the provision of pneumococcal immunization services, assesses [...] Read more.
Background: Pneumococcal vaccination rates in the United States (US) remain suboptimal, especially for adults aged 19 to 64 with high-risk medical conditions. Community-pharmacy-based immunization services increase vaccine access, particularly in rural areas. This study describes the provision of pneumococcal immunization services, assesses the processes used to identify and confirm patient eligibility, and determines barriers to immunization services in rural community pharmacies. Methods: A cross-sectional survey was emailed to members of the Rural Research Alliance of Community Pharmacies, located in the southeastern US. The survey assessed which pneumococcal vaccines were offered, age groups, prescription requirements, and how patient eligibility was determined. In addition, participants were asked to rate a series of patient-related and organizational barriers to pneumococcal vaccination. Results: Ninety-four pharmacies completed the survey, with most (96.8%) offering pneumococcal vaccines, most commonly PCV20 (95.6%). Most pharmacies vaccinated patients upon request (98.9%) or when patients presented with a prescription (82.4%), but few proactively contacted patients to schedule the vaccination (17.6%). Pharmacists most often administered pneumococcal vaccines to patients aged 65 and older and used patient age and immunization information systems to identify eligible patients. The most common patient-related barrier was the patient’s belief that they do not need the vaccine. The most common organizational barriers were inadequate reimbursements for vaccine administration and vaccine products. Conclusions: Pneumococcal vaccinations are commonly offered in rural community pharmacies, which play an important role in immunization access. With recent guideline changes to the age-based recommendation, there is an opportunity to optimize strategies to increase vaccine uptake. Full article
(This article belongs to the Section Vaccines against Infectious Diseases)
12 pages, 334 KiB  
Protocol
Clinical Course, Outcomes, and Risk Factors of Myocarditis and Pericarditis Following Administration of mRNA-1273 Vaccination: A Protocol for a Federated Real-World Evidence Vaccine Safety Study Using Data from Five European Data Sources
by Laura C. Zwiers, Diederick E. Grobbee, Rob Schneijdenberg, Corine Baljé, Samantha St. Laurent, Daina B. Esposito, Lei Zhu, Veronica V. Urdaneta, Magalie Emilebacker, Daniel Weibel, Felipe Villalobos, Carlo Alberto Bissacco, Arantxa Urchueguía Fornes, Juan José Carreras-Martínez, Anteneh A. Desalegn, Angela Lupattelli, Lei Wang, Jannik Wheler, Vera Ehrenstein, Denise Morris, Catherine Fry, Marjolein Jansen, Brianna M. Goodale and David S. Y. Ongadd Show full author list remove Hide full author list
Vaccines 2025, 13(7), 755; https://doi.org/10.3390/vaccines13070755 - 16 Jul 2025
Viewed by 527
Abstract
Background: Myocarditis and pericarditis are recognised risks following COVID-19 vaccination, including the mRNA-1273 vaccine. Most cases occur shortly following the second dose of this vaccine, and incidence is highest among young males. However, little is known about risk factors beyond age and [...] Read more.
Background: Myocarditis and pericarditis are recognised risks following COVID-19 vaccination, including the mRNA-1273 vaccine. Most cases occur shortly following the second dose of this vaccine, and incidence is highest among young males. However, little is known about risk factors beyond age and sex and about the longer-term clinical course. This study aims to identify possible risk factors for myocarditis and pericarditis following mRNA-1273 vaccination, to characterise the clinical course of myocarditis and pericarditis, both associated with mRNA-1273 vaccination and not associated with vaccination, and to identify risk factors for severe outcomes (i.e., cardiac or thromboembolic complications, severe hospital outcomes, all-cause hospital readmission, and death). Methods: This study is being conducted within the Vaccine Monitoring Collaboration for Europe (VAC4EU) association using routinely collected healthcare data from five data sources from four European countries (Denmark, Norway, Spain, and the United Kingdom). The study is being performed using a common data model, and all analyses are performed separately in each data source in a federated manner following a common protocol. A case–cohort analysis set is identified within each data source for identifying potential risk factors for myocarditis and pericarditis following mRNA-1273 vaccination using logistic regression analysis. The clinical course of myocarditis and pericarditis is being assessed using a cohort study design and describes all cases (i.e., cases associated with mRNA-1273 and unexposed cases). Cox regression analysis is applied to assess the associations between risk factors and several follow-up outcomes. Conclusions: This protocol describes the study methodology of an international collaborative initiative with the aim of assessing the risk factors and clinical course of myocarditis and pericarditis following mRNA-1273 vaccination using a federated network of five European data sources. Full article
(This article belongs to the Section Vaccine Advancement, Efficacy and Safety)
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13 pages, 554 KiB  
Review
Innate Immune Response to Powassan Virus Infection: Progress Toward Infection Control
by Mohammad Enamul Hoque Kayesh, Michinori Kohara and Kyoko Tsukiyama-Kohara
Vaccines 2025, 13(7), 754; https://doi.org/10.3390/vaccines13070754 - 15 Jul 2025
Viewed by 297
Abstract
Powassan virus is an emerging tick-borne flavivirus that poses a significant threat to human health. The outcome of Powassan virus infection is shaped by both viral factors and the host immune response. While this review aimed to examine the innate immune response, particularly [...] Read more.
Powassan virus is an emerging tick-borne flavivirus that poses a significant threat to human health. The outcome of Powassan virus infection is shaped by both viral factors and the host immune response. While this review aimed to examine the innate immune response, particularly toll-like receptor-mediated immune responses to Powassan virus, data specific to the immune response to Powassan virus remain scarce. Therefore, we focused on toll-like receptor responses to related flaviviruses to infer possible mechanisms of host response. Insights from both in vivo and in vitro studies are critical for guiding the development of effective therapeutic and preventive strategies. Currently, there are no clinically approved treatments or vaccines for Powassan virus, highlighting the urgent need for their development. We also highlight recent progress in POWV vaccine development, with an emphasis on the potential use of toll-like receptor agonists as adjuvants to enhance immunogenicity and improve vaccine efficacy. Full article
(This article belongs to the Special Issue Vaccines Against Flaviviruses and Alphaviruses: Recent Advances and Future Challenges—2nd Edition)
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15 pages, 1291 KiB  
Article
Development and Validation of a Standardized Pseudotyped Virus-Based Neutralization Assay for Assessment of Anti-Nipah Virus Neutralizing Activity in Candidate Nipah Vaccines
by Muntasir Alam, Md Jowel Rana, Asma Salauddin, Emma Bentley, Gathoni Kamuyu, Dipok Kumer Shill, Shafina Jahan, Mohammad Mamun Alam, Md Abu Raihan, Mohammed Ziaur Rahman, Rubhana Raqib, Ali Azizi and Mustafizur Rahman
Vaccines 2025, 13(7), 753; https://doi.org/10.3390/vaccines13070753 - 15 Jul 2025
Viewed by 1552
Abstract
Background: An effective vaccine against Nipah virus (NiV) is crucial due to its high fatality rate and recurrent outbreaks in South and Southeast Asia. Vaccine development is challenged by the lack of validated accessible neutralization assays, as virus culture requires BSL-4 facilities, restricting [...] Read more.
Background: An effective vaccine against Nipah virus (NiV) is crucial due to its high fatality rate and recurrent outbreaks in South and Southeast Asia. Vaccine development is challenged by the lack of validated accessible neutralization assays, as virus culture requires BSL-4 facilities, restricting implementation in resource-limited settings. To address this, we standardized and validated a pseudotyped virus neutralization assay (PNA) for assessing NiV-neutralizing antibodies in BSL-2 laboratories. Methods: The NiV-PNA was validated following international regulatory standards, using a replication-defective recombinant Vesicular stomatitis virus (rVSV) backbone dependent pseudotyped virus. Assessments included sensitivity, specificity, dilutional linearity, relative accuracy, precision, and robustness. The assay was calibrated using the WHO International Standard for anti-NiV antibodies and characterized reference sera to ensure reliable performance. Findings: Preliminary evaluation of the developed NiV-PNA showed 100% sensitivity and specificity across 10 serum samples (5 positive, 5 negative), with a positive correlation to a calibrated reference assay (R2 = 0.8461). Dilutional linearity (R2 = 0.9940) and accuracy (98.18%) were confirmed across the analytical titer range of 11-1728 IU/mL. The assay also exhibited high precision, with intra-assay and intermediate precision geometric coefficients of variation of 6.66% and 15.63%, respectively. Robustness testing demonstrated minimal variation across different pseudotyped virus lots, incubation times, and cell counts. Conclusions: The validated NiV-PNA is a reproducible and scalable assay platform for quantifying NiV neutralizing antibodies, offering a safer alternative to virus culture. Its validation and integration into the CEPI Centralized Laboratory Network will enhance global capacity for vaccine evaluation and outbreak preparedness. Full article
(This article belongs to the Section Vaccines against Infectious Diseases)
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15 pages, 250 KiB  
Article
Coverage and Vaccine Hesitancy of Influenza Vaccination Among Reproductive-Age Women (18–49 Years Old) in China: A National Cross-Sectional Study
by Jie Deng, Chenyuan Qin, Min Liu and Jue Liu
Vaccines 2025, 13(7), 752; https://doi.org/10.3390/vaccines13070752 - 14 Jul 2025
Viewed by 353
Abstract
Background: Influenza is a significant global respiratory infection, and vaccinating reproductive-age women, particularly in densely populated countries like China, cannot be overlooked. In this study, we aimed to determine influenza vaccination coverage, vaccine hesitancy, as well as associated factors among Chinese women [...] Read more.
Background: Influenza is a significant global respiratory infection, and vaccinating reproductive-age women, particularly in densely populated countries like China, cannot be overlooked. In this study, we aimed to determine influenza vaccination coverage, vaccine hesitancy, as well as associated factors among Chinese women aged 18–49 years old. Methods: A cross-sectional survey among women aged 18–49 years was conducted in China from 15 to 30 March 2023. We collected information such as past-year influenza vaccination, demographic characteristics, health-related factors, COVID-19-related factors, and perceived susceptibility and severity of influenza. Influenza vaccine acceptance among participants who did not receive influenza vaccination in the past year was also investigated. Multivariable logistic regression analyses were employed to investigate the influencing factors of vaccine coverage and vaccine hesitancy. Results: A total of 1742 reproductive-aged women were included in the final analysis. The past-year influenza vaccine coverage among women aged 18–49 years old was only 39.32% in China. Age ≥ 35 years (aOR = 0.72, 95% CI: 0.56–0.94), renting accommodation (aOR = 0.57, 95% CI: 0.44–0.75), and history of COVID-19 infection (aOR = 0.65, 95% CI: 0.47–0.89) and COVID-19 vaccine hesitancy (aOR = 0.39, 95% CI: 0.29–0.54) were all identified as negative correlates of influenza vaccine coverage among Chinese reproductive-aged women, while participants with a history of chronic diseases (aOR = 1.57, 95% CI: 1.23–2.01) and noticeable pandemic fatigue due to COVID-19 (aOR = 1.45, 95% CI: 1.05–2.00) were prone to have higher vaccination rates. Among reproductive-aged women who did not receive influenza vaccination in the past year, the hesitancy rate regarding future influenza vaccination was 31.79%. Factors such as older age, urban residence, living with others, poor self-rated health status, absence of chronic diseases, completion of full COVID-19 vaccination, COVID-19 vaccine hesitancy, pandemic fatigue, and failure to perceive the susceptibility and severity of influenza might increase influenza vaccine hesitancy. Discussion: Overall, a lower coverage rate of influenza vaccine was notably observed among Chinese reproductive-age women, as well as the hesitancy regarding future vaccination. To effectively mitigate the impact of influenza and reduce the incidence of associated diseases, it is imperative to devise targeted intervention strategies and policies tailored to reproductive-age women. Full article
(This article belongs to the Special Issue New Technology for Vaccines and Vaccine-Preventable Diseases)
12 pages, 1494 KiB  
Article
Breakthrough Infection After a Primary Series of COVID-19 Vaccination Induces Stronger Humoral Immunity and Equivalent Cellular Immunity to the Spike Protein Compared with Booster Shots
by Yoshifumi Uwamino, Takashi Yokoyama, Yasunori Sato, Shiho Tanaka, Yuka Kamoshita, Ayako Shibata, Toshinobu Kurafuji, Akiko Tanabe, Tomoko Arai, Akemi Ohno, Ho Namkoong, Tomoyasu Nishimura, Masatoshi Wakui, Mitsuru Murata, Naoki Hasegawa and Hiromichi Matsushita
Vaccines 2025, 13(7), 751; https://doi.org/10.3390/vaccines13070751 - 13 Jul 2025
Viewed by 385
Abstract
Background: The long-term immune implications of administering more than four doses of COVID-19 vaccine and the impact of breakthrough infections are not fully understood. Research Design and Methods: We conducted a follow-up cohort study on Japanese healthcare workers who received more than three [...] Read more.
Background: The long-term immune implications of administering more than four doses of COVID-19 vaccine and the impact of breakthrough infections are not fully understood. Research Design and Methods: We conducted a follow-up cohort study on Japanese healthcare workers who received more than three doses of the BNT162b2 vaccine. We assessed both the anti-SARS-CoV-2 antibody titer and cellular immunity in 429 participants and investigated the numbers, types, and brands of COVID-19 vaccines administered, as well as the episodes of COVID-19 infections after the third dose. Results: Individuals who received three total doses of vaccines with BTI episodes demonstrated higher antibody titers than those who received four total doses of vaccines with no BTIs. The cellular immune responses between these two groups were comparable. Conclusions: These findings suggest that BTIs occurring after the primary series of COVID-19 vaccinations (first to third dose) induced humoral immunity to the spike protein that is greater than that induced by booster doses (fourth or fifth dose) and elicit cellular immunity to the spike protein comparable to that of booster doses. Full article
(This article belongs to the Section COVID-19 Vaccines and Vaccination)
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11 pages, 723 KiB  
Article
The Anti-Nucleocapsid IgG Antibody as a Marker of SARS-CoV-2 Infection for Hemodialysis Patients
by Akemi Hara, Shun Watanabe, Toyoaki Sawano, Yuki Sonoda, Hiroaki Saito, Akihiko Ozaki, Masatoshi Wakui, Tianchen Zhao, Chika Yamamoto, Yurie Kobashi, Toshiki Abe, Takeshi Kawamura, Akira Sugiyama, Aya Nakayama, Yudai Kaneko, Hiroaki Shimmura and Masaharu Tsubokura
Vaccines 2025, 13(7), 750; https://doi.org/10.3390/vaccines13070750 - 13 Jul 2025
Viewed by 566
Abstract
Background: Hemodialysis patients, due to impaired kidney function and compromised immune responses, face increased risks from SARS-CoV-2. Anti-nucleocapsid IgG (anti-IgG N) antibodies are a commonly used marker to assess prior infection in the general population; however, their efficacy for hemodialysis patients remains unclear. [...] Read more.
Background: Hemodialysis patients, due to impaired kidney function and compromised immune responses, face increased risks from SARS-CoV-2. Anti-nucleocapsid IgG (anti-IgG N) antibodies are a commonly used marker to assess prior infection in the general population; however, their efficacy for hemodialysis patients remains unclear. Methods: A retrospective study of 361 hemodialysis patients evaluated anti-IgG N antibodies for detecting prior SARS-CoV-2 infection. Antibody levels were measured using a chemiluminescence immunoassay (CLIA) over the four time points. Boxplots illustrated antibody distribution across sampling stages and infection status. Logistic regression and receiver operating characteristic (ROC) curve analysis determined diagnostic accuracy, sensitivity, specificity, and optimal cutoff values. Results: Among the 361 hemodialysis patients, 36 (10.0%) had SARS-CoV-2 infection. Sex distribution showed a trend toward significance (p = 0.05). Boxplot analysis showed that anti-IgG N levels remained low in non-infected patients but increased in infected patients, peaking at the third sampling. Anti-IgG N demonstrated high diagnostic accuracy (AUC: 0.973–0.865) but declined over time (p = 0.00525). The optimal cutoff at C1 was 0.01 AU/mL (sensitivity 1.00, specificity 0.94). Adjusted models had lower predictive value. Conclusions: Anti-IgG N antibodies showed high diagnostic accuracy for detecting prior SARS-CoV-2 infection in hemodialysis patients, though performance declined over time. These findings highlight the need for tailored diagnostic strategies in this vulnerable population. Full article
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29 pages, 7767 KiB  
Article
Therapeutic Efficacy of CD34-Derived Allogeneic Dendritic Cells Engineered to Express CD93, CD40L, and CXCL13 in Humanized Mouse Models of Pancreatic Cancer
by Sara Huerta-Yepez, Jose D. Gonzalez, Neha Sheik, Senay Beraki, Elango Kathirvel, Ariel Rodriguez-Frandsen, Po-Chun Chen, Tiran Sargsyan, Saleemulla Mahammad, Mark R. Dybul, Lu Chen, Francois Binette and Anahid Jewett
Vaccines 2025, 13(7), 749; https://doi.org/10.3390/vaccines13070749 - 12 Jul 2025
Viewed by 814
Abstract
Background/Objectives: Pancreatic cancer remains the fourth leading cause of cancer-related deaths. While peripheral blood-derived mature dendritic cell (mDC) vaccines have shown potential in eliciting anti-tumor immune responses, clinical efficacy has been limited. This study aimed to enhance the potency and scalability of [...] Read more.
Background/Objectives: Pancreatic cancer remains the fourth leading cause of cancer-related deaths. While peripheral blood-derived mature dendritic cell (mDC) vaccines have shown potential in eliciting anti-tumor immune responses, clinical efficacy has been limited. This study aimed to enhance the potency and scalability of DC-based immunotherapy by developing an allogeneic DC platform derived from CD34+ hematopoietic stem cells (HSCs), genetically engineered to overexpress CD93, CD40L, and CXCL13, followed by maturation and tumor antigen pulsing. Methods: Engineered DCs were generated from CD34+ HSCs and matured in vitro after lentiviral transduction of CD93, CD40L, and CXCL13. Tumor lysates were used for antigen pulsing. A scrambled-sequence control DC was used for comparison. In vitro assays were performed to assess T cell activation and tumor cell killing. In vivo efficacy was evaluated using orthotopic pancreatic tumors in BLT and PBMC-humanized NSG mice established with the MiaPaca-2 (MP2) cell line. Results: Engineered DCs significantly enhanced T cell activation and tumor-specific cytotoxicity in vitro compared to control DCs. Antigen pulsing further amplified immune activation. In vivo, treated humanized mice showed increased CD4+, CD8+, and NK cell frequencies in peripheral blood and within tumors, correlating with reduced tumor burden. Conclusions: Our data shows that the antigen-pulsed, engineered DCs have the potency to activate immune cells, which leads to a significant reduction in pancreatic tumors and therefore could potentially provide an effective therapeutic opportunity for the treatment of pancreatic cancer and other solid tumors. Full article
(This article belongs to the Section Vaccination Against Cancer and Chronic Diseases)
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15 pages, 772 KiB  
Article
A Prospective Cohort Study of Primary Dengue Virus Infection in Medellín, Colombia
by Andrea Trujillo, Liesbeth Van Wesenbeeck, Lina Salazar, Liliana López, Lotke Tambuyzer, Annemie Buelens, Kim De Clerck, Oliver Lenz, Leen Vijgen, Marnix Van Loock, Guillermo Herrera-Taracena, Iván Darío Vélez and Freya Rasschaert
Vaccines 2025, 13(7), 748; https://doi.org/10.3390/vaccines13070748 - 12 Jul 2025
Viewed by 457
Abstract
Background: The evaluation of antiviral or vaccination strategies for the prevention of dengue infections in a traveler population would require extensive and complex studies. This prospective study aimed to identify a cohort of dengue naïve participants living in Medellín, a dengue endemic area, [...] Read more.
Background: The evaluation of antiviral or vaccination strategies for the prevention of dengue infections in a traveler population would require extensive and complex studies. This prospective study aimed to identify a cohort of dengue naïve participants living in Medellín, a dengue endemic area, as a proxy for travelers and to determine the incidence of primary dengue virus (DENV) infection (symptomatic and asymptomatic) in this cohort. In Colombia, epidemic dengue waves occur every 3–4 years, with infected Aedes mosquitoes present in ~80% of the territory, including Medellín. Methods: Participants > 16 years of age, living in Medellín, were screened for anti-DENV immunoglobulin G (IgG). DENV seronegative participants were enrolled in this study. A serological anti-DENV survey was performed, with semiannual sample collections for up to 2 years. Acute DENV infections were evaluated by monitoring fever and testing for DENV nonstructural protein 1 and/or RNA. Results: Of the 4885 screened participants, 3008 participants (62%) were DENV seronegative and enrolled. Among them, 2263 (75%) completed this study, and 2644 (88%) had at least one serosurvey visit after baseline. Of those, 52 (2%) had laboratory-confirmed DENV seroconversion, and 19 (<1%) had febrile illness, but none had laboratory-confirmed DENV infection. Conclusions: This study identified a cohort of predominantly students, seronegative at study start, living in Medellín and serving as a proxy for a prospective DENV infection traveler population. Laboratory-confirmed primary DENV infection was found in 2% of participants, with <1% reporting febrile illnesses, meeting the WHO criteria for probable clinical dengue cases. Full article
(This article belongs to the Special Issue Immune Response to Dengue Viral Infection)
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20 pages, 2013 KiB  
Systematic Review
Impact of Vaccination and Public Health Measures on the Severity of SARS-CoV-2 Omicron Infections in China: A Systematic Review and Meta-Regression Analysis
by Can Wang, Liping Peng, Xiaotong Huang and Tim K. Tsang
Vaccines 2025, 13(7), 747; https://doi.org/10.3390/vaccines13070747 - 12 Jul 2025
Viewed by 381
Abstract
Background: Starting in early 2022, SARS-CoV-2 Omicron has driven large outbreaks in China, a predominantly infection-naive population with high inactivated vaccine coverage. This unique context provided a substantially less-confounded opportunity to evaluate how vaccination, public health, and social measures influenced severity. Methods: We [...] Read more.
Background: Starting in early 2022, SARS-CoV-2 Omicron has driven large outbreaks in China, a predominantly infection-naive population with high inactivated vaccine coverage. This unique context provided a substantially less-confounded opportunity to evaluate how vaccination, public health, and social measures influenced severity. Methods: We systematically reviewed 86 studies (224 severity estimates) published from 2022 to 2024, reporting symptom and clinical severity outcomes (fever, cough, and sore throat; symptomatic, severe/critical, and fatal illness) of Omicron infections in China. Using meta-regression, we evaluated the associations of study setting, age group, vaccination status, predominant subvariants, and Oxford COVID-19 Government Response Tracker (OxCGRT) indices, including the Government Response Index (GRI), Containment and Health Index (CHI), and the Stringency Index (SI), with infection outcomes, adjusting for key confounders. Results: We found the primary or booster series of inactivated vaccines conferred strong protection against severe/critical illness (pooled relative risk (RR) 0.17 [95% CI: 0.09–0.33]) but did not reduce symptom frequency (RR 0.99 [95% CI: 0.95–1.02]). Each 10-unit increase in GRI or CHI was associated with 7% (95% CI: 1–12%) and 6% (95% CI: 1–10%) lower odds of symptomatic infection and 3% (95% CI: 1–4%) lower odds of severe/critical illness. Later subvariants (BA.5, BF.7, and XBB) showed 24–38% higher odds of upper respiratory symptoms versus BA.1. Conclusions: The data collection context significantly impacted severity estimates, with higher estimates from emergency hospitals. Overall, inactivated vaccines provided strong protection against severe/critical outcomes while stringent public health measures were associated with lower severity. Our findings underscore the importance of consistent and standardized protocols to produce reliable estimates of SARS-CoV-2 severity in evolving epidemiological contexts. Full article
(This article belongs to the Special Issue COVID Vaccines: Design, Development, and Immune Response Studies: 2nd Edition)
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18 pages, 4140 KiB  
Article
Immune Responses Induced by Recombinant Membrane Proteins of Mycoplasma agalactiae in Goats
by Beatriz Almeida Sampaio, Maysa Santos Barbosa, Matheus Gonçalves de Oliveira, Manoel Neres Santos Júnior, Bruna Carolina de Brito Guimarães, Emilly Stefane Souza Andres, Ágatha Morgana Bertoti da Silva, Camila Pacheco Gomes, Rafaela de Souza Bittencourt, Thiago Macêdo Lopes Correia, Lucas Santana Coelho da Silva, Jurandir Ferreira da Cruz, Rohini Chopra-Dewasthaly, Guilherme Barreto Campos, Jorge Timenetsky, Bruno Lopes Bastos and Lucas Miranda Marques
Vaccines 2025, 13(7), 746; https://doi.org/10.3390/vaccines13070746 - 11 Jul 2025
Viewed by 457
Abstract
Background/Objectives: Contagious agalactia (CA) is a disease typically caused by Mycoplasma agalactiae, affecting small ruminants worldwide and being endemic in certain countries. CA causes severe economic losses due to mastitis, agalactia, and arthritis. As an alternative to existing immunoprophylactic measures, this study [...] Read more.
Background/Objectives: Contagious agalactia (CA) is a disease typically caused by Mycoplasma agalactiae, affecting small ruminants worldwide and being endemic in certain countries. CA causes severe economic losses due to mastitis, agalactia, and arthritis. As an alternative to existing immunoprophylactic measures, this study aimed to develop a recombinant subunit vaccine against M. agalactiae and evaluate its specific immune response in goats. Methods: Goats were divided into three groups: group 1 received recombinant proteins (P40 and MAG_1560), group 2 received formalin-inactivated M. agalactiae, and group 3 received Tris-buffered saline (negative control). All solutions were emulsified in Freund’s adjuvant. Animals were monitored for 181 days. IgG antibody production was assessed by ELISA, and peripheral blood mononuclear cells (PBMCs) were analyzed by real-time PCR for the expression of IL-1β, IFN-γ, IL-12, and MHC class II genes. Results: M. agalactiae-specific antibody response was observed for six months in the sera of animals from group 1. Analysis of cytokine gene expression revealed increased IL-1β mRNA levels over time in both experimental groups. In group 1, IFN-γ mRNA levels increased with P40 stimulation and decreased with MAG_1560. IL-12 mRNA expression decreased over time in group 1 with P40 stimulation, whereas group 2 showed increased IL-12 expression for both proteins. MHC-II expression was stimulated in both groups. Conclusions: The recombinant proteins induced antibody production and cytokine expression, demonstrating immunogenic potential and supporting their promise as vaccine candidates capable of eliciting both humoral and cellular immune responses against M. agalactiae. Full article
(This article belongs to the Section Veterinary Vaccines)
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