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Vaccines
Volume 13
Issue 3
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Vaccines, Volume 13, Issue 3 (March 2025) – 127 articles

Cover Story (view full-size image): Bovine respiratory syncytial virus (BRSV) is a major pathogen in calves, responsible for severe respiratory outbreaks. Its high mutation rate leads to genetic diversity, potentially affecting vaccine efficacy. In this study, we identified strains from subgroups II and VIII circulating in Wallonia, Belgium, with subgroup VIII being documented for the first time in the country. Current vaccines are based on strains from subgroups II and III, raising questions about their effectiveness, particularly against subgroup VIII. The continuous evolution of BRSV highlights the need for sustained surveillance to guide vaccine strategies. Given its widespread distribution, monitoring viral diversity in other countries is crucial for effective disease control. View this paper
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14 pages, 2032 KiB  
Article
Stakeholders Perspectives on the Introduction of an Additional Injectable Vaccine Under the Universal Immunization Programme in India
by Pawan Kumar, Rashmi Mehra, Arindam Ray, Amrita Kumari, Kapil Singh, Rhythm Hora, Amanjot Kaur, Seema S. Koshal, Syed F. Quadri, Shyam Kumar Singh, Abida Sultana and Arup Deb Roy
Vaccines 2025, 13(3), 334; https://doi.org/10.3390/vaccines13030334 - 20 Mar 2025
Viewed by 182
Abstract
Introduction: In 2023, India’s National Technical Advisory Group on Immunization (NTAGI) recommended the inclusion of typhoid conjugate vaccine (TCV) in the Universal Immunization Programme (UIP). However, introducing TCV, an additional injectable vaccine (AIV), will potentially increase the number of injections administered in a [...] Read more.
Introduction: In 2023, India’s National Technical Advisory Group on Immunization (NTAGI) recommended the inclusion of typhoid conjugate vaccine (TCV) in the Universal Immunization Programme (UIP). However, introducing TCV, an additional injectable vaccine (AIV), will potentially increase the number of injections administered in a single visit to a maximum of five (if given at the 9 to 12 months touchpoint) or four (if given in the second year of life). In this context, the present study aimed to explore the perspectives of program managers, service providers, and caregivers regarding introduction of an AIV in a single visit under the UIP. Methods: A mixed-method study was undertaken wherein quantitative data was collected by telephonic surveys, and qualitative data by key informant interviews (KIIs) and focus group discussions (FGDs). Purposive sampling encompassed eight states, eight districts, eight planning units, and 32 session sites. The qualitative data were thematically analyzed manually using Excel, while the quantitative data was analyzed using STATA 17. Results: A total of 1140 telephonic surveys, 96 KIIs, and 16 FGDs were conducted. The study revealed that program managers mentioned maternal emotional reactions as a significant concern and backed AIV introduction at the 9–12 months touchpoint. Vaccinators and community mobilizers favored the 16–24 months window with combined presentations and mentioned single-dose vials as the preferred approach for vaccine delivery. Caregivers acknowledged the benefits of vaccination but expressed discomfort and fear regarding multiple injections to the child in a single visit. Caregivers expressed a preference for a combination vaccine. No preference was reported among caregivers for the introduction of AIV to the 9–12 or 16–24 months touchpoints. Conclusion: Stakeholders’ perspectives on introducing an additional injectable vaccine in a single visit under the UIP are diverse. These will be helpful in developing an effective strategy for the future introduction of AIV under UIP. Full article
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13 pages, 710 KiB  
Article
Pooled Analysis of the Effect of Pre-Existing Ad5 Neutralizing Antibodies on the Immunogenicity of Adenovirus Type 5 Vector-Based COVID-19 Vaccine from Eight Clinical Trials
by Wenqing Liu, Yuqing Li, Xiaolong Li, Feiyu Wang, Runjie Qi, Tao Zhu and Jingxin Li
Vaccines 2025, 13(3), 333; https://doi.org/10.3390/vaccines13030333 - 20 Mar 2025
Viewed by 167
Abstract
Background: Pre-existing adenovirus immunity restricts the utilization of adenovirus-vectored vaccines. The current study aims to conduct a pooled analysis of eight clinical trials to evaluate the influence of pre-existing Ad5 neutralizing antibodies on immunogenicity of Ad5-nCoV. Methods: The primary outcome indicator [...] Read more.
Background: Pre-existing adenovirus immunity restricts the utilization of adenovirus-vectored vaccines. The current study aims to conduct a pooled analysis of eight clinical trials to evaluate the influence of pre-existing Ad5 neutralizing antibodies on immunogenicity of Ad5-nCoV. Methods: The primary outcome indicator of this pooled analysis is the geometric mean titers (GMTs) of live SARS-CoV-2 NAbs against the wild-type strain on day 28 post-vaccination. Participants were divided into two cohorts: an adolescent cohort comprising individuals aged 6–17 years and an adult cohort with individuals aged 18 years and older. Within each cohort, individuals were further categorized into three subgroups based on their Ad5-nCoV vaccination schedules: one subgroup received a single intramuscular dose as the primary regimen (Ad5-IM-prime), another received an intramuscular dose as the heterologous prime-boost regimen (Ad5-IM-boost), and the last subgroup received an aerosolized dose as the heterologous prime-boost regimen (Ad5-IH-boost). Results: A total of 3512 participants were included in this pooled analysis. In the Ad5-IM-prime subgroup, there were 1001 adolescents and 1450 adults; in the Ad5-IM-boost subgroup, there were 65 adolescents and 396 adults; and in the Ad5-IH-boost subgroup, there were 207 adolescents and 393 adults. In the adult cohort, the GMTs of NAbs against wild-type SARS-CoV-2 on day 28 post-vaccination for the Ad5-IM-prime, Ad5-IM-boost, and Ad5-IH-boost subgroups were 35.6 (95% CI: 32.0, 39.7), 358.3 (95% CI: 267.6, 479.6), and 2414.1 (95% CI: 2006.9, 2904.0), respectively, with negative (less than 1:12) pre-existing NAb titers compared to 10.7 (95% CI: 9.1, 12.6), 116.9 (95% CI: 84.9, 161.1), and 762.7 (95% CI: 596.2, 975.8), respectively, with high (greater than 1:1000) pre-existing NAb titers. A similar trend was observed in the adolescent cohort, where pre-existing immunity was found to reduce the peak of live SARS-CoV-2 Nabs post-vaccination. Conclusions: Regardless of whether Ad5-nCoV is administered as a primary vaccination regimen or as a heterologous prime-boost strategy, a negative impact on immunogenicity can still be observed in the presence of high pre-existing immunity. However, when primary immunization is achieved with inactivated COVID-19 vaccines, aerosol inhalation can significantly enhance the immunogenicity of Ad5-nCoV compared to intramuscular injections of Ad5-nCoV as a booster. Full article
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15 pages, 669 KiB  
Systematic Review
Comparative Analysis of Health Economic Evaluations for Different Influenza Vaccines and Vaccination Strategies in China: A Systematic Review
by Fanxu Kong, Li Cai, Jiayi Zhang, Huijie Zhu, Zhibin Peng, Jiandong Zheng, Yaming Zheng and Hai Fang
Vaccines 2025, 13(3), 332; https://doi.org/10.3390/vaccines13030332 - 20 Mar 2025
Viewed by 158
Abstract
Objective: This study systematically reviews health economic evaluations of influenza vaccines in China and synthesizes the evidence on different vaccine categories. Methods: We searched databases, including the China Hospital Knowledge Database, Wanfang, PubMed, Web of Science, and Embase, for studies on the health [...] Read more.
Objective: This study systematically reviews health economic evaluations of influenza vaccines in China and synthesizes the evidence on different vaccine categories. Methods: We searched databases, including the China Hospital Knowledge Database, Wanfang, PubMed, Web of Science, and Embase, for studies on the health economics of influenza vaccines in China from 2015 to 2024. Studies were selected based on predefined criteria, and relevant data were extracted for analysis. The research utilized a parameter, ICER/threshold, defined as the ICER divided by the GDP per capita, to compare the results of cost-effectiveness analysis (CEA) studies. Results: A total of 1743 articles were identified, of which 25 met the inclusion criteria for full-text review. These included 19 Chinese studies and 6 English studies. Study populations were predominantly older adults (52.0%), followed by children, adolescents, people with chronic disease, and pregnant women. Vaccination strategies included trivalent inactivated influenza vaccine (TIV), quadrivalent inactivated influenza vaccine (QIV), trivalent live-attenuated influenza vaccine (LAIV), and non-vaccination groups. For TIV, 94.7% reported positive cost-effectiveness or cost-benefit results, with 21.1% identifying it as the most dominant strategy. For QIV, six studies compared it with a non-vaccinated group, and five (83.3%) reported favorable economic results. The study on LAIV showed cost-effectiveness compared to no vaccination, but not compared to QIV. The ICER threshold for TIV is the most favorable, and the population that exhibits the highest cost-effectiveness and benefit from vaccination is those people with underlying health conditions. Conclusions: TIV vaccination is often cost-effective, especially for people with chronic diseases, children, and older adults. Prioritizing TIV vaccination for those people with chronic diseases is recommended. Full article
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17 pages, 1940 KiB  
Article
Application of Humanized MHC Transgenic Mice in the Screening of HLA–Restricted T Cell Epitopes for Influenza Vaccines
by Yuwei Wei, Keyu Sun, Xuelian Han, Yali Sun, Jiejie Zhang, Yuan Wang, Qi Yin, Tiantian Yang, Kai Yuan, Min Li and Guangyu Zhao
Vaccines 2025, 13(3), 331; https://doi.org/10.3390/vaccines13030331 - 20 Mar 2025
Viewed by 130
Abstract
Background: Annual influenza epidemics pose a significant burden on the global healthcare system. The currently available vaccines mainly induce the production of neutralizing antibodies against hemagglutinin and neuraminidase, which are prone to antigenic variation, and this can reduce vaccine efficacy. Vaccines designed to [...] Read more.
Background: Annual influenza epidemics pose a significant burden on the global healthcare system. The currently available vaccines mainly induce the production of neutralizing antibodies against hemagglutinin and neuraminidase, which are prone to antigenic variation, and this can reduce vaccine efficacy. Vaccines designed to target T cell epitopes can be potentially valuable. Considering the difficulties in obtaining clinical samples and the unique advantages of mice in disease-related research, a mouse model that can simulate human immune responses can be a superior alternative to peripheral blood mononuclear cells for epitope screening. Methods: The T cell epitopes of the A/California/07/2009 (H1N1) virus were predicted and utilized to evaluate the cellular immune responses of HLA-A2/DR1 and HLA-A11/DR1 transgenic mice during epitope screening. The selected peptides were used to immunize these two groups of transgenic mice, followed by a viral challenge to assess their protective efficacy. Results: The epitopes that were predicted and screened could stimulate cellular immune responses in HLA-A2/DR1 transgenic mice, HLA-A11/DR1 transgenic mice, and C57BL/6 mice. Moreover, the transgenic mice exhibited stronger ability to produce IFN-γ than that of the wild-type mice. Upon immunization and subjecting to viral challenge, the selected peptides exhibited protective effects against the influenza virus. Conclusions: The HLA-A2/DR1 and HLA-A11/DR1 transgenic mouse models can be used for the direct screening and validation of influenza virus T cell epitopes, which is crucial for designing T cell epitope vaccines against influenza viruses. Further, this method can be applied in epitope screening and vaccine designing before the spread of other emerging and sudden infectious diseases, thereby supporting epidemic control. Full article
(This article belongs to the Special Issue Immunity to Influenza Viruses and Vaccines)
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25 pages, 1446 KiB  
Review
Exploring CD169+ Macrophages as Key Targets for Vaccination and Therapeutic Interventions
by Rianne G. Bouma, Aru Z. Wang and Joke M. M. den Haan
Vaccines 2025, 13(3), 330; https://doi.org/10.3390/vaccines13030330 - 20 Mar 2025
Viewed by 200
Abstract
CD169 is a sialic acid-binding immunoglobulin-like lectin (Siglec-1, sialoadhesin) that is expressed by subsets of tissue-resident macrophages and circulating monocytes. This receptor interacts with α2,3-linked Neu5Ac on glycoproteins as well as glycolipids present on the surface of immune cells and pathogens. CD169-expressing macrophages [...] Read more.
CD169 is a sialic acid-binding immunoglobulin-like lectin (Siglec-1, sialoadhesin) that is expressed by subsets of tissue-resident macrophages and circulating monocytes. This receptor interacts with α2,3-linked Neu5Ac on glycoproteins as well as glycolipids present on the surface of immune cells and pathogens. CD169-expressing macrophages exert tissue-specific homeostatic functions, but they also have opposing effects on the immune response. CD169+ macrophages act as a pathogen filter, protect against infectious diseases, and enhance adaptive immunity, but at the same time pathogens also exploit them to enable further dissemination. In cancer, CD169+ macrophages in tumor-draining lymph nodes are correlated with better clinical outcomes. In inflammatory diseases, CD169 expression is upregulated on monocytes and on monocyte-derived macrophages and this correlates with the disease state. Given their role in promoting adaptive immunity, CD169+ macrophages are currently investigated as targets for vaccination strategies against cancer. In this review, we describe the studies investigating the importance of CD169 and CD169+ macrophages in several disease settings and the vaccination strategies currently under investigation. Full article
(This article belongs to the Special Issue Vaccines Targeting Dendritic Cells)
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13 pages, 932 KiB  
Article
Interplay Between Viral Shedding, Age, and Symptoms in Individual Infectivity of COVID-19 Breakthrough Infections in Households
by Shuaibing Dong, Ying Sun, Shuyu Ni, Yi Tian, Zhaomin Feng, Lei Jia, Xiaoli Wang, Daitao Zhang, Quanyi Wang, Tim K. Tsang and Peng Yang
Vaccines 2025, 13(3), 329; https://doi.org/10.3390/vaccines13030329 - 19 Mar 2025
Viewed by 153
Abstract
Background/Objectives: Understanding the factors influencing breakthrough infections following COVID-19 vaccination is critical for disease prevention, especially in households where transmission risks are high. Factors such as age, symptoms, living conditions, and viral load contribute to household transmission dynamics. Methods: To elucidate this complex [...] Read more.
Background/Objectives: Understanding the factors influencing breakthrough infections following COVID-19 vaccination is critical for disease prevention, especially in households where transmission risks are high. Factors such as age, symptoms, living conditions, and viral load contribute to household transmission dynamics. Methods: To elucidate this complex interplay of these factors, we analyzed a detailed household transmission study of COVID-19 involving 839 households and 1598 vaccinated individuals during the Omicron variant outbreak in Beijing, China, from April to June 2022. Using multivariate logistic regression models, we analyzed the impact of demographic, environmental, clinical, and virological factors on the risk of breakthrough infections. Results: In multivariate analysis. we estimated that index cases aged 45–59 and 60+ years were associated with 80% (95% confidence interval [CI]: 35%, 140%) and 288% (95% CI: 160%, 481%) higher infectivity compared with index cases aged 18–44 years. We estimated that index cases with fever, headache and cough were associated with 43% (95% CI: 11%, 84%), 78% (95% CI: 18%, 168%) and 67% (25%, 123%) higher infectivity compared with those without. Index cases with higher viral loads were associated with higher infectivity in univariate analysis, but this was no longer significant in multivariate analysis. Smaller living space and two-member households were associated with higher odds of breakthrough infections. Conclusions: Age, symptoms, and living conditions were significant risk factors for breakthrough infections during the Omicron outbreak. Suburban settings, smaller spaces, and two-member households enhance transmission risks. These findings inform targeted interventions to reduce household transmission. Full article
(This article belongs to the Special Issue Communicable Diseases: New and Old Therapies and Preventive Strategies)
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16 pages, 3875 KiB  
Article
Immunogenicity and Safety of the Bivalent Respiratory Syncytial Virus Prefusion F Subunit Vaccine in Immunocompromised or Renally Impaired Adults
by Natalia Castillo Almeida, Lalitha Parameswaran, Elliot N. DeHaan, Hayley Wyper, Farah Rahman, Qin Jiang, Wen Li, Michael Patton, Maria Maddalena Lino, Zaynah Majid-Mahomed, Elissa Malkin, Matthew Davis, William J. Towner, Kapil Saharia, Kumar Ilangovan, Elena Kalinina, David Cooper, Kena A. Swanson, Annaliesa S. Anderson, Alejandra Gurtman and Iona Munjaladd Show full author list remove Hide full author list
Vaccines 2025, 13(3), 328; https://doi.org/10.3390/vaccines13030328 - 19 Mar 2025
Viewed by 460
Abstract
Background/Objectives: Individuals with immunocompromising conditions are at high risk of developing severe respiratory syncytial virus (RSV) illness. This phase 3, single-arm study assessed the safety and immunogenicity of the bivalent RSV prefusion F protein−based (RSVpreF) 120-µg vaccine in immunocompromised and renally impaired adults. [...] Read more.
Background/Objectives: Individuals with immunocompromising conditions are at high risk of developing severe respiratory syncytial virus (RSV) illness. This phase 3, single-arm study assessed the safety and immunogenicity of the bivalent RSV prefusion F protein−based (RSVpreF) 120-µg vaccine in immunocompromised and renally impaired adults. Methods: Participants were stratified by age group (18−<60-year-olds; ≥60-year-olds) and received two RSVpreF doses 1 month apart (i.e., Dose 1 and Dose 2, respectively). Reactogenicity events were collected for 7 days after each dose; adverse events through 1 month after the last dose; and serious adverse events, adverse events of special interest, and newly diagnosed chronic medical conditions throughout the study. Results: One month after Dose 1, RSVpreF elicited robust immune responses overall and across age and immunocompromised subgroups. Overall, geometric mean fold rises from before to 1 month after Dose 1 were high for RSV A and RSV B (8.3 and 9.0, respectively); no additional increases 1 month after Dose 2 (7.5 and 7.8) were observed. The most frequent local reaction was pain at the injection site, which was more common after Dose 2 than after Dose 1. The most frequent systemic event after any dose was fatigue. Most local reactions and systemic events were mild or moderate in severity. Adverse event and serious adverse event rates were 13.5% and 7.3% among 18−<60-year-olds and 22.4% and 14.0% among ≥60-year-olds, respectively. Conclusions: A single dose of the RSVpreF vaccine conferred robust immune responses in immunocompromised and renally impaired adults with no safety concerns. (ClinicalTrials.gov Identifier: NCT05842967). Full article
(This article belongs to the Special Issue Current Development of Vaccines for Respiratory Viral Infection)
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25 pages, 11367 KiB  
Article
An mRNA Vaccine for Herpes Zoster and Its Efficacy Evaluation in Naïve/Primed Murine Models
by Linglei Jiang, Wenshuo Zhou, Fei Liu, Wenhui Li, Yan Xu, Zhenwei Liang, Man Cao, Li Hou, Pengxuan Liu, Feifei Wu, Aijun Shen, Zhiyuan Zhang, Xiaodi Zhang, Haibo Zhao, Xinping Pan, Tengjie Wu, William Jia and Yuntao Zhang
Vaccines 2025, 13(3), 327; https://doi.org/10.3390/vaccines13030327 - 19 Mar 2025
Viewed by 327
Abstract
Background/Objectives: An overwhelming burden to clinics, herpes zoster (HZ), or shingles, is a painful disease that occurs frequently among aged individuals with a varicella-zoster virus (VZV) infection history. The cause of shingles is the reactivation of dormant VZV in the dorsal root ganglia/cranial [...] Read more.
Background/Objectives: An overwhelming burden to clinics, herpes zoster (HZ), or shingles, is a painful disease that occurs frequently among aged individuals with a varicella-zoster virus (VZV) infection history. The cause of shingles is the reactivation of dormant VZV in the dorsal root ganglia/cranial nerves of the human body. Patients with HZ experience sharp, intense, electric shock-like pain, which makes their health-related quality of life (HRQoL) extremely low. Methods: Various mRNA constructs were designed based on intracellular organelle-targeting strategies and AI algorithm-guided high-throughput automation platform screening and were then synthesized by in vitro transcription and encapsulated with four-component lipid nanoparticles (LNPs). Immunogenicity was evaluated on a naïve mouse model, long-term mouse model, and VZV-primed mouse model. Safety was evaluated by a modified “nestlet shredding” method for potential adverse effects induced by vaccines. Comparison between muscular and intradermal administrations was conducted using different inoculated approaches as well. Results: The best vaccine candidate, CVG206, showed robust humoral and cellular immune responses, durable immune protection, and the fewest adverse effects. The CVG206 administered intradermally revealed at least threefold higher humoral and cellular immune responses compared to intramuscular vaccination. The manufactured and lyophilized patch of CVG206 demonstrated good thermal stability at 2–8 °C during 9 months of storage. Conclusions: The lyophilized mRNA vaccine CVG206 possesses remarkable immunogenicity, long-term protection, safety, and thermal stability, and its effectiveness could even be further improved by intradermal administration, revealing that CVG206 is a promising vaccine candidate for HZ in future clinical studies. Full article
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10 pages, 1111 KiB  
Article
Cell-Based Relative Potency of a Respiratory Syncytial Virus mRNA Vaccine Correlates with In Vivo Immunogenicity
by Katrina Feller, Hesham Nawar, Liping Song, Amanda Abrams, Liang Shang, Ashley Gruber, Tatyana Yun and Hualin Helen Li
Vaccines 2025, 13(3), 326; https://doi.org/10.3390/vaccines13030326 - 19 Mar 2025
Viewed by 204
Abstract
Background/Objectives: Potency is a critical quality attribute for vaccine development as well as clinical drug product (DP) lot release and stability testing. Animal studies have the potential to offer conclusive insights about the potency of vaccines by demonstrating technical relevance with respect to [...] Read more.
Background/Objectives: Potency is a critical quality attribute for vaccine development as well as clinical drug product (DP) lot release and stability testing. Animal studies have the potential to offer conclusive insights about the potency of vaccines by demonstrating technical relevance with respect to the hypothesized vaccine mode of action. However, animal studies are expensive, time-consuming, labor intensive, and, most importantly, involve the use of animals. Therefore, alternative in vitro potency assays should be explored. Methods: In this study, female BALB/c mice were immunized intramuscularly with various doses of a respiratory syncytial virus (RSV) mRNA vaccine V171 lots at day 0 and day 21. Vaccine-elicited immune responses were determined by ELISA (post-dose 1) and neutralizing assay (post-dose 2). These vaccine lots were also tested in a cell-based relative potency assay in which the ability of each lot to express the RSV F protein in Hep G2 cells was measured against a reference standard. Results: Effective Dose 50s (ED50s) of the vaccine lots were determined with probit models based on dichotomized ELISA or neutralizing titers. Statistical analysis demonstrated that the post-dose 2 neutralizing ED50 correlates with cell-based relative potency (Pearson’s correlation test ln (RP) and ln (ED50): correlation coefficient = −0.82; p-value = 0.047). Conclusions: These data merit the use of a cell-based potency assay to replace the animal study to support V171 vaccine development and to use for DP lot release and stability testing. This study also establishes proof-of-concept of using cell-based potency assays as an alternative to animal immunogenicity studies for mRNA-based vaccines. Full article
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19 pages, 687 KiB  
Article
Determinants of Ukrainian Mothers’ Intentions to Vaccinate Their Children in Poland: A Cross-Sectional Study
by Katarzyna Lewtak, Joanna Mazur, Harriet Dwyer, Agnieszka Sochoń-Latuszek, Anastasiya Atif, Tomasz Maciejewski and Dorota Kleszczewska
Vaccines 2025, 13(3), 325; https://doi.org/10.3390/vaccines13030325 - 19 Mar 2025
Viewed by 241
Abstract
Background/Objectives: In 2022, the full-scale invasion in Ukraine forced over 6 million Ukrainians, primarily mothers and children, to seek safety outside of the country. This massive influx has posed a significant challenge to the Polish healthcare system, particularly regarding routine vaccination for children. [...] Read more.
Background/Objectives: In 2022, the full-scale invasion in Ukraine forced over 6 million Ukrainians, primarily mothers and children, to seek safety outside of the country. This massive influx has posed a significant challenge to the Polish healthcare system, particularly regarding routine vaccination for children. This study aims to examine the vaccination intentions of displaced Ukrainian mothers, their compliance with the Polish National Immunisation Programme (PNIP), and the factors that influence these intentions. Methods: A web-based survey (June–July 2023) was conducted among Ukrainian mothers in Poland. The questionnaire assessed the importance placed on vaccination, knowledge of PNIP, and concerns related to displacement and vaccination. Hierarchical logistic regression identified key determinants. Results: Among 2572 respondents, 64.5% reported that their children had received only some or none of the recommended vaccines. Key barriers included unfamiliarity with PNIP, limited knowledge of vaccines, and concerns about vaccine side effects. Of mothers whose children had not followed PNIP, 41.7% intended to vaccinate, 33.1% refused, and 25.2% were undecided. Regression analysis identified perception of vaccination importance as the strongest predictor. Partial adherence to PNIP doubled vaccination likelihood, while a firm plan to return to Ukraine reduced it 2.4 times. Mistrust in vaccines increased refusal risk tenfold. The final model confirmed mothers’ attitudes towards vaccination and future plans (return to Ukraine) as dominant factors. Conclusions: This study underscores the complex determinants shaping vaccination decisions in conflict-displaced communities. It provides insights for public health strategies to enhance vaccine uptake by reducing access barriers, restoring trust, and strengthening vaccine literacy. Full article
(This article belongs to the Section Human Vaccines and Public Health)
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13 pages, 2789 KiB  
Article
Targeted Delivery of Personalized Cancer Vaccines Based on Antibody–Antigen Complexes
by Yaling Zhang, Lingling Yan, He Sun, Ziyi Zhang, Fengyun Shen and Lele Sun
Vaccines 2025, 13(3), 324; https://doi.org/10.3390/vaccines13030324 - 19 Mar 2025
Viewed by 203
Abstract
Background: Personalized cancer vaccines based on tumor neoantigens show great potential in cancer immunotherapy due to their high safety and specificity. However, it is inherently difficult to realize the efficiently targeted delivery of personalized cancer vaccines to antigen-presenting cells (APCs). Methods: This study [...] Read more.
Background: Personalized cancer vaccines based on tumor neoantigens show great potential in cancer immunotherapy due to their high safety and specificity. However, it is inherently difficult to realize the efficiently targeted delivery of personalized cancer vaccines to antigen-presenting cells (APCs). Methods: This study aimed to address these challenges by developing and evaluating a personalized cancer vaccine based on antibody–antigen complexes, which was designed to enhance antitumor effects by increasing the utilization of tumor neoantigens by APCs. Mice were immunized with a carrier protein, keyhole limpet hemocyanin (KLH), to induce the production of antibodies against KLH. Subsequently, mice were immunized with KLH loaded with tumor neoantigens and the immunoadjuvant CpG ODN and underwent immunological analysis to evaluate the immune and antitumor effects. Results: The results showed that preimmunization with KLH could promote the uptake of the personalized KLH-based tumor vaccine, which was enhanced by dendritic cells (DCs) and macrophages (Mφs), by strengthening the T-cell immune responses to tumors. Conclusions: Collectively, this work provides a new idea for the targeted delivery of personalized cancer vaccines. Full article
(This article belongs to the Special Issue Advances in Cancer Immunotherapy and Vaccines Research: 2nd Edition)
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16 pages, 1730 KiB  
Article
Cost-Effectiveness of Adjuvanted Influenza Vaccine Compared with Standard and High-Dose Influenza Vaccines for Persons Aged ≥50 Years in Spain
by Alberto Perez-Rubio, Roberto Flores, Jesus Ruiz Aragon, Javier Sanchez, Sergio Marquez-Peláez, Piedad Alvarez, Andres Osorio Muriel and Joaquin Mould-Quevedo
Vaccines 2025, 13(3), 323; https://doi.org/10.3390/vaccines13030323 - 19 Mar 2025
Viewed by 342
Abstract
Background: The prevalence of chronic conditions that increase the risk of influenza complications is high among individuals aged ≥50 years, and evidence suggests age-related changes in immune responses to vaccines begin to decline at this age. Persons aged 50–59 years have high rates [...] Read more.
Background: The prevalence of chronic conditions that increase the risk of influenza complications is high among individuals aged ≥50 years, and evidence suggests age-related changes in immune responses to vaccines begin to decline at this age. Persons aged 50–59 years have high rates of influenza infections and are also the most likely age group to be employed. Thus, the burden of influenza is high in this age group. Methods: We investigated the cost-effectiveness of vaccination with an adjuvanted quadrivalent influenza vaccine (aQIV) in a Spanish population aged ≥50 years at high risk of influenza complications. Using a static decision-tree model specifically designed to analyze Spanish data, we calculated incremental cost-effectiveness ratios (ICERs) for aQIV vs. egg-based QIV (QIVe; indicated for any age) and aQIV vs. high-dose QIV (HD-QIV; indicated for persons aged ≥60 years) from payer and societal perspectives. We compared ICERs against a willingness-to-pay threshold of EUR 25,000 per quality-adjusted life year (QALY) gained. The impact of input uncertainty on ICER was evaluated through a probabilistic sensitivity analysis (PSA) and a one-way deterministic sensitivity analysis (DSA). Results: The total incremental cost of vaccination with aQIV was EUR –86,591,967.67, which was associated with gains of 241.02 in QALY (EUR –359,268.05 per QALY gained) and 318.04 in life years (EUR −272,271.37 per life year gain). Compared with the willingness-to-pay threshold of EUR 25,000 per QALY gained, aQIV was the most cost-effective influenza vaccine relative to the combination of QIVe or HD-QIV. These findings were supported by PSA and DSA analyses. Conclusions: In the model, aQIV dominated QIVe and HD-QIV, demonstrating that aQIV use would be cost-saving for persons aged ≥50 years who are at high risk of influenza complications. Full article
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19 pages, 310 KiB  
Article
Beyond Vaccination: Exploring Young Adults’ Awareness, Knowledge, and Attitudes Related to Sexually Transmitted Infections in Romania
by Alexandra-Ioana Roșioară, Bogdana Adriana Năsui, Nina Ciuciuc, Dana Manuela Sîrbu, Daniela Curșeu, Romulus Florian Oprica, Codruța Alina Popescu, Rodica Ana Ungur, Tamara Cheșcheș and Monica Popa
Vaccines 2025, 13(3), 322; https://doi.org/10.3390/vaccines13030322 - 18 Mar 2025
Viewed by 294
Abstract
Background and Objectives: Romania has the highest rate of cervical cancer in Europe. The aim of this study is to measure the level of sexual health knowledge among participants and determine the extent to which factors such as age, gender, education level, access [...] Read more.
Background and Objectives: Romania has the highest rate of cervical cancer in Europe. The aim of this study is to measure the level of sexual health knowledge among participants and determine the extent to which factors such as age, gender, education level, access to sexual health resources, and cultural background influence their knowledge. Materials and Methods: A cross-sectional study was conducted on 1089 Romanian youth participants aged 18–35 years. A self-administered online questionnaire was used concerning the level of knowledge relating to STIs, contraception methods, and preventive attitudes during the 2023–2024 academic year. Results: Most of the participants (93,8%) scored a “good-to-excellent” STI level of knowledge. Despite this, 71.9% of the responders had never taken an HIV test, and 63.5% had never been tested for other STIs. Logistic regression analysis revealed a direct association between higher STI knowledge levels among respondents with age (p < 0.001), underage sexual debuts (p = 0.018), greater parental education (p = 0.016), and those who studied health sciences (p < 0.001). Conclusions: This study highlights the critical need for health communication campaigns to enhance STI knowledge and vaccine literacy to improve the vaccination rates among young people in Romania. The identified knowledge gaps, frequent misconceptions, and barriers to STI testing underscore the importance of comprehensive sexual health education, public health initiatives for reducing the stigma associated with STIs, and improved access to healthcare services for young people. Full article
(This article belongs to the Special Issue Vaccine Development and Global Health)
18 pages, 1301 KiB  
Review
The Use of Residual Blood Specimens in Seroprevalence Studies for Vaccine-Preventable Diseases: A Scoping Review
by Monica Pilewskie, Christine Prosperi, Abigail Bernasconi, Ignacio Esteban, Lori Niehaus, Connor Ross, Andrea C. Carcelen, William J. Moss and Amy K. Winter
Vaccines 2025, 13(3), 321; https://doi.org/10.3390/vaccines13030321 - 18 Mar 2025
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Abstract
Background: Residual blood specimens offer a cost- and time-efficient alternative for conducting serological surveys. However, their use is often criticized due to potential issues with the representativeness of the target population and/or limited availability of associated metadata. We conducted a scoping review [...] Read more.
Background: Residual blood specimens offer a cost- and time-efficient alternative for conducting serological surveys. However, their use is often criticized due to potential issues with the representativeness of the target population and/or limited availability of associated metadata. We conducted a scoping review to examine where, when, how, and why residual blood specimens have been used in serological surveys for vaccine-preventable diseases (VPDs) and how potential selection biases are addressed. Methods: The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines and identified relevant papers published in 1990–2022. Results: A total of 601 articles met the inclusion criteria after title, abstract screening, and full-text review. The most studied VPDs using residual blood specimens were COVID-19 (27%), hepatitis E (16%), hepatitis B (10%), influenza (9%), HPV (7%), and measles (7%). Residual blood specimens were primarily sourced from diagnostic specimens (61%) or blood and plasma donations (37%). Almost all articles used specimens linked to basic demographic data (e.g., age and sex), with 47% having access to extended demographic data (e.g., geographic location). Common strategies to address potential biases included comparing results with published estimates (78%) and performing stratified analyses (71%). Conclusions: Residual blood specimens are widely used in seroprevalence studies, particularly during emerging disease outbreaks when rapid estimates are critical. However, this review highlighted inconsistencies in how researchers analyze and report the use of residual specimens. We propose a set of recommendations to improve the analysis, reporting, and ethical considerations of serological surveys using residual specimens. Full article
(This article belongs to the Section Human Vaccines and Public Health)
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10 pages, 1085 KiB  
Brief Report
Four-Color Pseudovirus-Based Neutralization Assay: A Rapid Method for Evaluating Neutralizing Antibodies Against Quadrivalent Hand, Foot, and Mouth Disease Vaccine
by Fan Gao, Lingjie Xu, Qian Wang, Gang Wang, Mingchen Liu, Lu Li, Qian He, Xuanxuan Zhang, Ying Wang, Qunying Mao, Zhenglun Liang, Tao Wang, Xiao Ma and Xing Wu
Vaccines 2025, 13(3), 320; https://doi.org/10.3390/vaccines13030320 - 18 Mar 2025
Viewed by 196
Abstract
Background/Objectives: Enterovirus 71 (EV71) and coxsackieviruses A16 (CA16), A10 (CA10), and A6 (CA6) are the primary pathogens that cause hand, foot, and mouth disease (HFMD). Currently, many manufacturers are developing bivalent, trivalent, and tetravalent vaccines that target these antigens. Cell-based neutralization assay (CBNA), [...] Read more.
Background/Objectives: Enterovirus 71 (EV71) and coxsackieviruses A16 (CA16), A10 (CA10), and A6 (CA6) are the primary pathogens that cause hand, foot, and mouth disease (HFMD). Currently, many manufacturers are developing bivalent, trivalent, and tetravalent vaccines that target these antigens. Cell-based neutralization assay (CBNA), the gold standard for detecting neutralizing antibodies (NtAbs), which are used as indicators of HFMD vaccine efficacy, has several limitations. We aimed to develop a novel assay for detecting NtAbs against a quadrivalent HFMD vaccine. Methods: We developed a four-color pseudovirus-based neutralization assay (PBNA), utilizing fluorescent reporter genes, to rapidly evaluate neutralizing antibodies against EV71, CA16, CA10, and CA6 in multivalent vaccines and compared it with CBNA. Results: PBNA could rapidly and simultaneously detect NtAbs against the four serotypes and required lesser amounts of sera compared to CBNA. A good consistency in determining NtAb titers was observed for PBNA and CBNA. Conclusions: PBNA provides a robust tool for evaluating the efficacy of multivalent HFMD vaccines and conducting seroepidemiological studies. Full article
(This article belongs to the Section Pathogens-host Immune Interface)
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18 pages, 2706 KiB  
Article
Impact of the Implementation of a Bovine Viral Diarrhea Virus Targeted Vaccine in Dairy Farms: Longitudinal Analysis
by Demian Bellido, Diego Wenz, Martin Schang, Facundo Tibaldo Rubiolo, Pablo Mangioni, Emanuel Gumina, Andrés Wigdorovitz and Viviana Parreño
Vaccines 2025, 13(3), 319; https://doi.org/10.3390/vaccines13030319 - 17 Mar 2025
Viewed by 260
Abstract
Objective: This study evaluated the effect of a novel subunit-targeted vaccine against BVDV in six dairy farms in Argentina. Methods: Reproductive, health, and production parameters—including conception and abortion rates, open days, calves born per insemination, as well as newborn and overall mortality, and [...] Read more.
Objective: This study evaluated the effect of a novel subunit-targeted vaccine against BVDV in six dairy farms in Argentina. Methods: Reproductive, health, and production parameters—including conception and abortion rates, open days, calves born per insemination, as well as newborn and overall mortality, and milk production—were monitored over a ten-year period (2014–2023). Data were analyzed annually to assess trends and compare the periods before and after vaccine introduction. Results: All parameters showed significant improvement after vaccine incorporation, with an 11% increase in conception rate, a 5% reduction in abortion rate, a 12% increase in calves per insemination rate, and a decrease of 11 open days (8.4%). Additionally, newborn mortality and overall mortality decreased by 33% and 16%, respectively, while milk production increased by 9%. These data were also compared with eight non-vaccinated dairy farms, and significant differences were observed in health and reproductive parameters. Conclusions: These findings indicate that vaccination with an effective non-replicating subunit vaccine can successfully minimize the impact of BVDV in dairy farms. Full article
(This article belongs to the Section Veterinary Vaccines)
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4 pages, 141 KiB  
Editorial
COVID-19 and Transplant Patients: Challenges, Risks, and Evolving Strategies
by Mariarosaria Campise
Vaccines 2025, 13(3), 318; https://doi.org/10.3390/vaccines13030318 - 17 Mar 2025
Viewed by 251
Abstract
The first cases of COVID-19 were reported in December 2019 in Wuhan, China [...] Full article
(This article belongs to the Special Issue SARS-CoV-2 Infection and Vaccines for Patients with Renal Diseases)
17 pages, 5380 KiB  
Article
Antigen-Dependent Adjuvanticity of Poly(lactic-co-glycolic acid)-polyethylene Glycol 25% Nanoparticles for Enhanced Vaccine Efficacy
by Minxuan Cui, Jiayue Xi, Zhuoyue Shi, Yupu Zhu, Zhengjun Ma, Muqiong Li, Qian Yang, Chaojun Song and Li Fan
Vaccines 2025, 13(3), 317; https://doi.org/10.3390/vaccines13030317 - 16 Mar 2025
Viewed by 443
Abstract
Background: A key component in modern vaccine development is the adjuvant, which enhances and/or modulates the antigen-specific immune response. In recent years, nanoparticle (NP)-based adjuvants have attracted much research attention owing to their ability to enhance vaccine potency. Nonetheless, how the selection [...] Read more.
Background: A key component in modern vaccine development is the adjuvant, which enhances and/or modulates the antigen-specific immune response. In recent years, nanoparticle (NP)-based adjuvants have attracted much research attention owing to their ability to enhance vaccine potency. Nonetheless, how the selection of different antigens influences the overall vaccine efficacy when combined with the same nanoparticle adjuvant is less discussed, which is important for practical applications. Methods: Non-toxic mutants of exotoxin Hla (rHlaH35L) and cell-wall-anchored protein SpA(rSpam) were covalently conjugated to Poly(lactic-co-glycolic acid)-polyethylene glycol (PLGA-PEG) 25% NPs (25% NPs) as antigens to prepare nanovaccines. Antibody titers, cytokine secretion levels, and the antibody bacteriolytic capacity were tested to investigate immune activation. To evaluate the protective efficacy of the nanovaccine, immunized mice were challenged with S. aureus ATCC 25923 at three different lethal doses: 1 × LD100, 2 × LD100, and 4 × LD100. Results: We showed that 25% NP-rHlaH35L nanovaccines were associated with more efficient humoral, cellular, and innate immune responses and protection potency compared with 25% NP-rSpam. Moreover, the overall vaccine potency of 25% NP-rHlaH35L was even better than the combination vaccination of both 25% NP-rHlaH35L and 25% NP-rSpam. In comparison to the clinically used aluminum (alum) adjuvant, the 25% NP adjuvants were found to stimulate humoral and cellular immune responses efficiently, irrespective of the antigen type. For antigens, either exotoxins or cell-wall-anchored proteins, the 25% NP-based vaccines show excellent protection for mice from S. aureus infection with survival rates of 100% after lethal challenge, which is significantly superior to the clinically used alum adjuvant. Moreover, due to the superior immune response elicited by 25% NP-rHlaH35L, the animals inoculated with this formulation survived even after two times the lethal dose of S. aureus administration. Conclusions: We demonstrated that the type of antigen plays a key role in determining the overall vaccine efficacy in the immune system when different kinds of antigens are conjugated with a specific nanoparticle adjuvant, paving a new way for vaccine design based on 25% NP adjuvants with enhanced potency and reduced side effects. Full article
(This article belongs to the Special Issue Advance in Nanoparticles as Vaccine Adjuvants)
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23 pages, 2715 KiB  
Article
The Sm14+GLA-SE Recombinant Vaccine Against Schistosoma mansoni and S. haematobium in Adults and School Children: Phase II Clinical Trials in West Africa
by Amadou Tidjani Ly, Doudou Diop, Modou Diop, Anne-Marie Schacht, Abdoulaye Mbengue, Rokhaya Diagne, Marieme Guisse, Jean-Pierre Dompnier, Carolina Messias, Rhea N. Coler, Celso R. Ramos, Jacques-Noël Tendeng, Seynabou Ndiaye, Miryam Marroquin-Quelopana, Juçara de Carvalho Parra, Tatiane dos Santos, Marília Sirianni dos Santos Almeida, Daniella Arêas Mendes-da-Cruz, Steven Reed, Wilson Savino, Gilles Riveau and Miriam Tendleradd Show full author list remove Hide full author list
Vaccines 2025, 13(3), 316; https://doi.org/10.3390/vaccines13030316 - 16 Mar 2025
Viewed by 493
Abstract
Background/Objectives: Following previous successful Phase I clinical trials conducted in men and women in a non-endemic area for schistosomiasis in Brazil, the Sm14 vaccine was evaluated in an endemic region in Senegal. We report successful clinical trials in adults (Phase IIa) and school [...] Read more.
Background/Objectives: Following previous successful Phase I clinical trials conducted in men and women in a non-endemic area for schistosomiasis in Brazil, the Sm14 vaccine was evaluated in an endemic region in Senegal. We report successful clinical trials in adults (Phase IIa) and school children (Phase IIb), respectively, of a Schistosoma mansoni 14 kDa fatty acid-binding protein (Sm14) vaccine + a glucopyranosyl lipid A (GLA-SE) adjuvant. Methods: Participants were evaluated based on clinical assessments, laboratory tests (including hematologic and biochemical analyses of renal and hepatic functions), and immunological parameters (humoral and cellular responses) up to 12 months after the first vaccination dose in the Phase IIa trial and after 120 days in the Phase IIb trial. Results: The results showed strong immunogenic responses and good tolerance in both adults and children, with no major adverse effects. Importantly, significant increases in Sm14-specific total IgG (IgG1 and IgG3) were observed as early as 30 days after the first vaccination, with high titres remaining at least 120 days afterwards. Sm14-specific total IgG serum levels were also significantly enhanced in adults and in both infected and non-infected, vaccinated children and elicited robust cytokine responses with increased TNFα, IFN-γ, and IL-2 profiles. Conclusions: Overall, the Sm14+GLA-SE vaccine is safe and highly immunogenic, with a clearly protective potential against schistosomiasis, supporting progression to the next Phase III clinical trials. Full article
(This article belongs to the Special Issue The Development of Vaccine Against Parasite Infection)
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13 pages, 2723 KiB  
Article
Stabilizing Prefusion SARS-CoV-2 Spike by Destabilizing the Postfusion Conformation
by Debajyoti Chakraborty, Randhir Singh, Raju S. Rajmani, Sahil Kumar, Rajesh P. Ringe and Raghavan Varadarajan
Vaccines 2025, 13(3), 315; https://doi.org/10.3390/vaccines13030315 - 14 Mar 2025
Viewed by 434
Abstract
Background/Objectives: As with many viral fusion proteins, the native conformation of SARS-CoV-2 Spike is metastable. Most COVID-19 vaccines utilize a stabilized Spike (Spike-2P) containing two proline substitutions, and subsequently, a further stabilized variant with four additional proline substitutions, Spike-6P, has been developed. In [...] Read more.
Background/Objectives: As with many viral fusion proteins, the native conformation of SARS-CoV-2 Spike is metastable. Most COVID-19 vaccines utilize a stabilized Spike (Spike-2P) containing two proline substitutions, and subsequently, a further stabilized variant with four additional proline substitutions, Spike-6P, has been developed. In an alternative approach, we introduced two aspartic acid residues (2D) in the HR1 region of Spike at positions that are exposed and buried in the pre- and postfusion states, respectively, to destabilize the postfusion conformation. Methods: The recombinant protein constructs were expressed in a mammalian cell culture and characterized for their yield and antigenicity, and the formulations were then used to immunize hamsters. After two immunizations, the hamsters were challenged with live B.1.351 SARS-CoV-2 virus for an evaluation of the protective efficacy. Results: The introduction of the two aspartic acid mutations resulted in an approximately six-fold increase in expression, comparable to that in Spike-2P. When the 2D mutations were combined with the above four proline mutations (Spike-4P-2D), this led to a further three- to four-fold enhancement of protein expression, similar to that seen in Spike-6P. When formulated with the oil-in-water emulsion adjuvant Sepivac SWE, the 2P, 2D, 6P, and 4P-2D Spike variants all protected female hamsters against heterologous challenge with the B.1.351 SARS-CoV-2 virus and elicited high titers of neutralizing antibodies. Conclusions: We suggest that destabilization of the postfusion conformation through the introduction of charged amino acids at sites that are exposed in the pre- and buried in the postfusion conformation offers a general strategy to enhance the yield and stability of the native, prefusion conformation of viral surface proteins. Full article
(This article belongs to the Special Issue SARS-CoV-2 Variants, Vaccines, and Immune Responses)
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20 pages, 3038 KiB  
Article
Anti-Tumor Efficacy of a Mesothelin-Based Nanovaccine in a KPC Orthotopic Mouse Model of Pancreatic Cancer
by Daniele P. Ferrari, Özmen Çobanoglu, Sana Sayedipour, Omar Luna, Sonia A. M. Ferkel, David Agorku, Yomkippur Perez, Luis J. Cruz, Fernando Albericio, François Trottein, Frauke Alves, Marietta Andrea Markus and Fernanda Ramos-Gomes
Vaccines 2025, 13(3), 314; https://doi.org/10.3390/vaccines13030314 - 14 Mar 2025
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Abstract
Background/Objectives: Immunotherapy has shown promising results in some cancers, but its efficacy remains limited in pancreatic ductal adenocarcinoma (PDAC). Vaccines in nanoparticle form (nanovaccines) can incorporate immunostimulating components to induce a potent immune response. As mesothelin (MSLN) is a tumor-associated antigen overexpressed [...] Read more.
Background/Objectives: Immunotherapy has shown promising results in some cancers, but its efficacy remains limited in pancreatic ductal adenocarcinoma (PDAC). Vaccines in nanoparticle form (nanovaccines) can incorporate immunostimulating components to induce a potent immune response. As mesothelin (MSLN) is a tumor-associated antigen overexpressed in PDAC, we evaluated the effect of MSLN nanovaccine in a syngeneic orthotopic KPC-PDAC mouse model. Methods: An MSLN peptide combining three MSLN epitopes and two adjuvants, poly I:C and R848, was encapsulated in PLGA–chitosan nanoparticles to generate the nanovaccine. Results: The MSLN nanovaccine was successfully taken up by dendritic cells in vitro and was found in inguinal lymph nodes 24 h after subcutaneous injection into C57BL/6 mice. Nanovaccine re-stimulation of splenocytes from vaccinated mice led to increased levels of interferon-γ in vitro compared to unstimulated splenocytes. Higher levels of MSLN-specific IgM and IgG antibodies were detected in the serum of vaccinated mice compared to that of control mice. Three vaccination regimens were tested: a prophylactic scheme that included vaccination before tumor induction and two therapeutic schemes involving early and late vaccination after tumor cell inoculation. MSLN nanovaccination inhibited KPC tumor progression and metastasis and induced higher CD8+ T cell infiltration in the tumor that developed in response to prophylactic and early therapeutic schedules but not in response to a later vaccination approach. Although the nanovaccine treatment elicited higher humoral and cellular antigen-specific responses in tumor-bearing mice for both vaccination strategies, the therapeutic vaccination also increased the expression of exhaustion markers in CD8+ T cells. Conclusions: Our results support the relevance of an MSLN-based nanovaccine as a new immunotherapy treatment for PDAC and propose an innovative method of vaccine delivery using NPs. Full article
(This article belongs to the Section Cancer Vaccines and Immunotherapy)
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15 pages, 2786 KiB  
Article
Effect of Anti-Programmed Cell Death-1 Antibody on Middle Ear Mucosal Immune Response to Intranasal Administration of Haemophilus influenzae Outer Membrane Protein
by Kazuhiro Yoshinaga, Takashi Hirano, Shingo Umemoto, Yoshinori Kadowaki, Takayuki Matsunaga and Masashi Suzuki
Vaccines 2025, 13(3), 313; https://doi.org/10.3390/vaccines13030313 - 13 Mar 2025
Viewed by 266
Abstract
Background/Objectives: Acute otitis media is a common pediatric infection caused primarily by nontypeable Haemophilus influenzae. With rising antibiotic resistance, vaccines are essential for combating this public health issue. Although the PD-1/PD-L1 pathway has been extensively studied for its role in tumor [...] Read more.
Background/Objectives: Acute otitis media is a common pediatric infection caused primarily by nontypeable Haemophilus influenzae. With rising antibiotic resistance, vaccines are essential for combating this public health issue. Although the PD-1/PD-L1 pathway has been extensively studied for its role in tumor immunity, its impact on mucosal immunity, particularly in vaccine responses, is unclear. Methods: BALB/c mice were intranasally immunized with nontypeable H. influenzae outer membrane protein and treated with anti-PD-L1 antibodies. Immune responses were evaluated in middle ear mucosa (MEM), the cervical lymph node, and the spleen using an enzyme-linked immunosorbent assay, an enzyme-linked immunospot assay, and flow cytometry. The effects on CD4+ T cells, T follicular helper (Tfh) cells, and B-cell differentiation were analyzed. Results: Anti-PD-L1 antibody treatment increased CD3+CD4+CD185+ (CXCR5+) Tfh cells in MEM, which play a crucial role in supporting B-cell activation and antibody production. This correlated with a significant increase in IgA- and IgG-producing cells in MEM, which enhanced local bacterial clearance. Although B-cell activation and differentiation into plasmablasts were observed in MEM, no significant changes were noted in the cervical lymph node and spleen, suggesting a localized enhancement of mucosal immunity. Conclusions: Anti-PD-L1 antibodies promoted Tfh cell expansion and B-cell differentiation in MEM, leading to enhanced antibody production and improved bacterial clearance. These findings suggest that PD-L1 blockade can potentiate mucosal vaccine-induced immunity by strengthening local humoral responses. This supports its potential application in developing intranasal vaccines for acute otitis media. Full article
(This article belongs to the Special Issue Mucosal Immunity and Vaccine)
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21 pages, 3596 KiB  
Article
Robust COVID-19 Vaccine Responses Despite Filarial Co-Infection: Insights from a Lymphatic Filariasis Cohort in Ghana
by Julia Meyer, Jennifer Nadal, Linda Batsa Debrah, Alexander Yaw Debrah, Jubin Osei-Mensah, Derrick Adu Mensah, Patricia Jebett Korir, Janina M. Kuehlwein, Ute Klarmann-Schulz, Achim Hoerauf and Tomabu Adjobimey
Vaccines 2025, 13(3), 312; https://doi.org/10.3390/vaccines13030312 - 13 Mar 2025
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Abstract
Background/Objectives: Although the COVID-19 pandemic has largely concluded, the varied trajectories it has followed in different regions of the world remain incompletely understood. Intensive research is needed to fully grasp its course and the implications for future global health challenges. Notably, the milder [...] Read more.
Background/Objectives: Although the COVID-19 pandemic has largely concluded, the varied trajectories it has followed in different regions of the world remain incompletely understood. Intensive research is needed to fully grasp its course and the implications for future global health challenges. Notably, the milder trajectory of the COVID-19 pandemic in Sub-Saharan Africa has defied initial predictions. An emerging body of evidence suggests that, in addition to the continent’s younger average age and the lower prevalence of relevant comorbidities, co-infections with helminths may have also impressively shaped the pandemic’s milder trajectory in the region. Indeed, helminths are renowned for their ability to modulate human immune responses, which, while potentially beneficial in limiting excessive inflammation, could also diminish vaccine efficacy and impede viral clearance. This study investigated different aspects of the intricate interactions between COVID-19 and Lymphatic Filariasis (LF), a helminth infection caused by parasitic worms such as Wuchereria bancrofti, Brugia malayi, and Brugia timori and endemic to various regions in Sub-Saharan Africa and the tropics. Methods: For this purpose, samples of a larger and ongoing clinical trial (ethical approval codes: CHRPE/AP/525/17 and 325/21; trial registration number ISRCTN14042737) were collected from 222 individuals from endemic areas of Ghana, along with comprehensive clinical and demographic data. The samples include LF patients (n = 222) grouped according to their Lymphoedema (LE) stages, as well as COVID-19 vaccinated (n = 81) and non-vaccinated individuals (n = 141). All vaccinated participants received the COVID-19 vaccine ChAdOx1-S (also known as Vaxzevria) developed by the University of Oxford and AstraZenca. The expressions of SARS-CoV-2 and filarial-specific antibodies (IgG, IgA) were accessed using ELISA, while Luminex-based immunoassays were employed to measure the expression of SARS-CoV-2 variant-specific neutralizing antibodies. The interplay between vaccine responses and demographic factors was analyzed using group comparisons with the Kruskal-Wallis or Mann-Whitney U tests. Results: The results indicate that a remarkable portion of unvaccinated individuals (56% IgA seropositive, 39% IgG seropositive) developed antibodies against SARS-CoV-2 despite no confirmed infection. Notably, the study identified a robust antibody response to COVID-19 vaccination, which was independent of the degree of LF pathology or parasitic status. An important observation was the reduced SARS-CoV-2 antibody response in individuals seropositive for Ascaris lumbricoides (p = 0.0264), highlighting an interaction between roundworm infection and COVID-19. Conclusions: The study concludes that the ChAdOx1-S COVID-19 vaccine (AstraZeneca) triggers a strong immune response in LF patients; however, filarial and/or soil-transmitted helminth seropositivity might influence the COVID-19 infection-induced response. These findings emphasize the complexity of infectious disease dynamics in co-infected populations and the need to decipher parasite-induced immunomodulatory mechanisms on COVID-19 vaccination. Full article
(This article belongs to the Special Issue Emerging Insights: Vaccine Efficacy and Clinical Dynamics in the Context of Multiple Pathogen Exposures)
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27 pages, 2149 KiB  
Article
Inflammatory and Humoral Immune Responses to Commercial Autogenous Salmonella Bacterin Vaccines in Light-Brown Leghorn Pullets: Primary and Secondary Vaccine Responses
by Chrysta N. Beck, Jossie M. Santamaria and Gisela F. Erf
Vaccines 2025, 13(3), 311; https://doi.org/10.3390/vaccines13030311 - 13 Mar 2025
Viewed by 203
Abstract
Background/Objectives: Commercial poultry flocks undergo Salmonella vaccinations to manage salmonellosis outbreaks. Due to reports of severe injection site reactions to Salmonella bacterins, assessment of local inflammatory responses is necessary. The objective was to assess local inflammatory and systemic humoral immune responses to commercial [...] Read more.
Background/Objectives: Commercial poultry flocks undergo Salmonella vaccinations to manage salmonellosis outbreaks. Due to reports of severe injection site reactions to Salmonella bacterins, assessment of local inflammatory responses is necessary. The objective was to assess local inflammatory and systemic humoral immune responses to commercial autogenous Salmonella bacterin vaccines (SV1 or SV2) following primary or secondary intradermal (i.d.) vaccination in Light-Brown Leghorns (LBLs). Methods: LBL pullets received primary (14 wks) or secondary (19 wks) vaccination by i.d. growing feather (GF) pulp injection of SV1, SV2, Salmonella Enteritidis (SE) lipopolysaccharide (LPS), or water–oil–water emulsion (V). Local leukocyte levels and relative cytokine mRNA expression were monitored before (0 d) and at 6 h, 1 d, 2 d, 3 d, 5 d, and 7 d post-GF pulp injection (p.i.). Blood was collected through 28 d post-primary or -secondary vaccination, and SE-specific antibodies were quantified via ELISA. Results: Primary vaccine administration increased local heterophil and macrophage levels and increased IL-6 and IL-8 mRNA expressions at 6 h p.i., independent of treatment. Secondary administration extended these local immune activities through 3 d p.i. and included prolonged IL-17A mRNA expression. Primary and secondary GF-pulp injection with V resulted in rapid lymphocyte recruitment by 6 h p.i., comprised primarily of CD4+ and γδ T cells. SV1 and SV2 also produced a T-dependent systemic humoral immune response, as indicated by the IgM-to-IgG isotype switch, along with a memory phenotype in the secondary response. Conclusions: These commercial-killed Salmonella vaccines, when prepared in water–oil–water emulsions, stimulated prolonged innate and T helper (Th) 17-type inflammatory responses at the injection site and produced a classic systemic humoral immune response after a second vaccination. Further research is needed to determine if extended inflammation influences adaptive immune responses in eliminating Salmonella infection. Full article
(This article belongs to the Special Issue Novel Vaccine Designs to Enhance the Engagement of Innate and Adaptive Immunity)
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11 pages, 532 KiB  
Article
Immune Imprinting, Non-Durable Hybrid Immunity, and Hybrid Immune Damping Following SARS-CoV-2 Primary Vaccination with BNT162b2 and Boosting with mRNA-1273
by Alejo Erice, Néstor Nuño, Lola Prieto and Cristina Caballero
Vaccines 2025, 13(3), 310; https://doi.org/10.3390/vaccines13030310 - 13 Mar 2025
Viewed by 360
Abstract
Background/Objectives: Long-term studies on the immune response following multiple doses of SARS-CoV-2 mRNA vaccines remain limited. Methods: Secondary analyses of data from a cohort of non-immunocompromised subjects who received two doses of BNT162b2 (primary vaccination) and a booster with mRNA-1273 nine months later. [...] Read more.
Background/Objectives: Long-term studies on the immune response following multiple doses of SARS-CoV-2 mRNA vaccines remain limited. Methods: Secondary analyses of data from a cohort of non-immunocompromised subjects who received two doses of BNT162b2 (primary vaccination) and a booster with mRNA-1273 nine months later. Antibodies targeting the receptor-binding domain of the S1 subunit of the SARS-CoV-2 spike (anti-RBD) were measured at eight time points during follow-up; the SARS-CoV-2-specific T cell response was measured 16 and 25 months after primary vaccination using an interferon-γ release assay. Results: During the 9-month follow up period after primary vaccination and before the mRNA-1273 booster, anti-RBD were significantly higher at all time points in subjects with documented SARS-CoV-2 infection before the first study time point (previously infected subjects; n = 50) compared to naïve subjects (n = 208; p < 0.05). During a 16-month follow up period following the mRNA-1273 booster, anti-RBD were lower at all time points in previously infected subjects (n = 21) compared to naïve subjects (n = 109), although the differences were non-significant. Breakthrough SARS-CoV-2 infections increased over time in both groups, particularly after the mRNA-1273 booster. Most participants had a persistent SARS-CoV-2 specific T cell response regardless of prior infection. Conclusions: These findings suggest a modulating effect of previous SARS-CoV-2 infection on the humoral immune response to mRNA vaccination, a non-durable hybrid immunity following mRNA vaccination in previously infected subjects, and attenuation of the humoral immune response (immune damping) after repeated exposure to SARS-CoV-2 antigens through mRNA vaccination and/or infection. Full article
(This article belongs to the Special Issue SARS-CoV-2 Variants, Vaccines, and Immune Responses)
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14 pages, 274 KiB  
Article
The Effectiveness of Four Quadrivalent, Inactivated Influenza Vaccines Administered Alone or in Combination with Pneumococcal and/or SARS-CoV-2 Vaccines: A Population-Wide Cohort Study
by Cecilia Acuti Martellucci, Annalisa Rosso, Enrico Zauli, Alessandro Bianconi, Matteo Fiore, Graziella Soldato, Patrizia Marani Toro, Marco De Benedictis, Graziano Di Marco, Roberto Carota, Rossano Di Luzio, Maria Elena Flacco and Lamberto Manzoli
Vaccines 2025, 13(3), 309; https://doi.org/10.3390/vaccines13030309 - 13 Mar 2025
Viewed by 468
Abstract
Background: Several influenza vaccine formulations are available, including adjuvanted, high-dose, trivalent, and quadrivalent vaccines, and direct, comparative evidence on the relative effectiveness is limited. Real-life data on the potential impact of the co-administration of pneumococcal and/or SARS-CoV-2 vaccinations are also very scarce. [...] Read more.
Background: Several influenza vaccine formulations are available, including adjuvanted, high-dose, trivalent, and quadrivalent vaccines, and direct, comparative evidence on the relative effectiveness is limited. Real-life data on the potential impact of the co-administration of pneumococcal and/or SARS-CoV-2 vaccinations are also very scarce. During the 2023–2024 influenza season, we carried out a retrospective cohort study on the entire elderly population of the Pescara province, Italy, in order to evaluate the effectiveness of the quadrivalent influenza vaccine, offered alone or in combination with other recommended vaccinations. Methods: All the immunization, demographic, co-payment, and hospitalization data were extracted from the official National Healthcare System, and the follow-up lasted from October 2023 to September 2024. The outcomes were all-cause mortality and hospital admissions for influenza and/or pneumonia. All the Cox models were adjusted (or stratified) for gender, age, hypertension, diabetes, COPD, CVD, renal disorders, cancer, and previous SARS-CoV-2 infection. Results: Overall, 43.9% of the population aged ≥60 years received an influenza vaccine (n = 46,355/105,527). A total of 3188 (3.0%) and 1047 (1.0%) individuals died of any cause or were hospitalized for influenza and/or pneumonia, respectively. During the follow-up, compared with the unvaccinated, those who received an influenza vaccine showed almost half the likelihood of death (adjusted HR: 0.52; 95%CI: 0.49–0.56) and hospitalization (aHR: 0.55; 95%CI: 0.48–0.62), regardless of the gender and age group. As compared with sole influenza immunization, the co-administration of a pneumococcal or COVID-19 vaccine was associated with a significantly lower risk of both outcomes. No substantial differences were observed by influenza vaccine formulation (MF59 adjuvanted; non-adjuvanted, standard dose; non-adjuvanted, high dose), with the exception of a greater mortality reduction for the MF59-adjuvanted vaccine as compared with the high-dose formulation. Conclusions: During the influenza season 2023–2024, all the influenza vaccines were largely effective among the elderly, with no substantial differences by formulation, age, or gender. However, the co-administration of a pneumococcal and/or SARS-CoV-2 vaccine further reduced the risk of both death and hospitalization. Specific, head-to-head randomized trials are required to confirm both findings. Full article
(This article belongs to the Special Issue Pharmacoepidemiology in Vaccine Safety and Efficacy)
13 pages, 922 KiB  
Review
Vaccination Strategies: Mixing Paths Versus Matching Tracks
by Achilleas Livieratos, Charalambos Gogos, Iason Thomas and Karolina Akinosoglou
Vaccines 2025, 13(3), 308; https://doi.org/10.3390/vaccines13030308 - 13 Mar 2025
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Abstract
Vaccination strategies play a pivotal role in achieving broad and robust immune protection. With the advent of new technologies and challenges posed by emerging infectious diseases such as SARS-CoV-2, evaluating the efficacy of homologous (matching tracks) and heterologous (mixing paths) vaccination regimens is [...] Read more.
Vaccination strategies play a pivotal role in achieving broad and robust immune protection. With the advent of new technologies and challenges posed by emerging infectious diseases such as SARS-CoV-2, evaluating the efficacy of homologous (matching tracks) and heterologous (mixing paths) vaccination regimens is critical. This article explores mechanistic insights and empirical evidence on the benefits and limitations of these approaches. Full article
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12 pages, 879 KiB  
Perspective
The Mpox Response Among Key Populations at High Risk of or Living with HIV in Rwanda: Leveraging the Successful National HIV Control Program for More Impactful Interventions
by Gallican Rwibasira, Tafadzwa Dzinamarira, Jean Claude Semuto Ngabonziza, Albert Tuyishime, Ayman Ahmed and Claude Mambo Muvunyi
Vaccines 2025, 13(3), 307; https://doi.org/10.3390/vaccines13030307 - 13 Mar 2025
Viewed by 296
Abstract
Mpox, an emerging zoonotic infectious disease, presents a significant public health threat, especially among high-risk groups like female sex workers and men who have sex with men. This commentary reviews and summarizes Rwanda’s response to mpox, focusing on its intersection with HIV. Rwanda [...] Read more.
Mpox, an emerging zoonotic infectious disease, presents a significant public health threat, especially among high-risk groups like female sex workers and men who have sex with men. This commentary reviews and summarizes Rwanda’s response to mpox, focusing on its intersection with HIV. Rwanda has adopted an integrated strategy to tackle both mpox and HIV by leveraging lessons and experience from the country’s success in the management of HIV and COVID-19, enhancing community engagement and health outcomes. To ensure long-term resilience, Rwanda must continue to invest in surveillance and research, expand vaccination efforts, address stigma, and foster regional impactful partnerships. Investing in fostering scientific and operational research will generate invaluable evidence that could lead to the implementation of evidence-based policymaking and cost-effective interventions. Full article
(This article belongs to the Special Issue Strategies for the Monitoring, Treatment, and Prevention of Mpox and Other Poxvirus Infections)
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21 pages, 663 KiB  
Systematic Review
Intestinal Microbiota and Vaccinations: A Systematic Review of the Literature
by Francesco Loddo, Pasqualina Laganà, Caterina Elisabetta Rizzo, Serena Maria Calderone, Bruno Romeo, Roberto Venuto, Daniele Maisano, Francesco Fedele, Raffaele Squeri, Alessandro Nicita, Antonio Nirta, Giovanni Genovese, Linda Bartucciotto and Cristina Genovese
Vaccines 2025, 13(3), 306; https://doi.org/10.3390/vaccines13030306 - 12 Mar 2025
Viewed by 401
Abstract
Background: Vaccination constitutes a low-cost, safe, and efficient public health measure that can help prevent the spread of infectious diseases and benefit the community. The fact that vaccination effectiveness varies among populations, and that the causes of this are still unclear, indicates [...] Read more.
Background: Vaccination constitutes a low-cost, safe, and efficient public health measure that can help prevent the spread of infectious diseases and benefit the community. The fact that vaccination effectiveness varies among populations, and that the causes of this are still unclear, indicates that several factors are involved and should be thoroughly examined. The “intestinal microbiota” is the most crucial of these elements. Numerous clinical studies demonstrate the intestinal microbiota’s significance in determining the alleged “immunogenicity” and efficacy of vaccines. This systematic review aimed to review all relevant scientific literature and highlight the role of intestinal microbiota in COVID-19, Salmonella typhi, Vibrio cholerae, and rotavirus vaccinations. Materials and Methods: The MESH terms “vaccines” and “microbiota” were used to search the major scientific databases PubMed, SciVerse Scopus, Web of Knowledge, and the Cochrane Central Register of Controlled Clinical Trials. Results: Between February 2024 and October 2024, the analysis was conducted using electronic databases, yielding a total of 235 references. Finally, 24 RCTs were chosen after meeting all inclusion criteria: eight studies of COVID-19, two studies of Salmonella typhi, three studies of Vibrio cholerae, and eleven studies of rotavirus. Only six of these demonstrated good study quality with a Jadad score of three or four. Conclusions: According to the review’s results, the intestinal microbiota surely plays a role in vaccinations’ enhanced immunogenicity, especially in younger people. As it is still unclear what mechanisms underlie this effect, more research is needed to better understand the role of the intestinal microbiota. Full article
(This article belongs to the Section Clinical Immunology)
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11 pages, 2876 KiB  
Article
Bacillus Calmette–Guérin Vaccination Promotes Efficient and Comprehensive Immune Modulation in Guinea Pig Models
by In-Ohk Ouh, Min Jung Kim, Kwangwook Kim, Heeji Lim, Ye Jin Yang, Ji Woong Heo, Han Nim Choi, Hun Hwan Kim, Hu-Jang Lee, Phil-Ok Koh, Seo Young Moon, Eun Bee Choi, Yoo-Kyung Lee and Kwang Il Park
Vaccines 2025, 13(3), 305; https://doi.org/10.3390/vaccines13030305 - 12 Mar 2025
Viewed by 287
Abstract
Background/Objectives: Tuberculosis (TB), caused by Mycobacterium tuberculosis H37Rv (M. tuberculosis), primarily affects the lungs. The Bacillus Calmette–Guérin (BCG) vaccine is the only available TB vaccine. Guinea pigs serve as an excellent preclinical model due to the similarity to human Tuberculosis pathology. [...] Read more.
Background/Objectives: Tuberculosis (TB), caused by Mycobacterium tuberculosis H37Rv (M. tuberculosis), primarily affects the lungs. The Bacillus Calmette–Guérin (BCG) vaccine is the only available TB vaccine. Guinea pigs serve as an excellent preclinical model due to the similarity to human Tuberculosis pathology. However, the lack of a standardized vaccination protocol in guinea pigs causes inconsistencies in efficacy assessments, limiting precise evaluation and its application in vaccine studies. This study aims to address this gap by establishing a consistent and reliable protocol for evaluating the immunological efficacy of BCG vaccination. Methods: Guinea pigs were divided into control, M. tuberculosis-infected, and BCG-vaccinated groups. Four weeks post-vaccination, the infected and vaccinated groups were challenged with M. tuberculosis. The bacterial burden in the lungs and spleen was measured, histopathological changes were analyzed using hematoxylin and eosin (H&E) staining, and the infection levels of M. tuberculosis, as well as the presence of interleukin-2 (IL-2), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ) positive cells, were evaluated through immunohistochemical (IHC) staining. Results: BCG vaccination reduced the bacterial load to 3.60 × 104 CFU/lung and 5.52 × 103 CFU/spleen compared to 3.78 × 105 CFU/lung and 1.54 × 104 CFU/spleen in the infected group. The mean histopathological score for lungs was 1.67 compared to 2.67 in the infected group. Similarly, the mean histopathological score for the spleen was 1.33 compared to 2.33 in the infected group. IHC analysis showed a notable reduction in M. tuberculosis and inflammatory cytokine-positive cells in the vaccinated group. The TNF-α, IL-2, and IFN-γ staining intensity decreased by 9.3, 4.8, and 11, respectively, compared to the infected group. Conclusions: This protocol enhances consistency in vaccine assessments, providing a reliable benchmark for the development of safer, more effective, and accessible TB vaccines. Full article
(This article belongs to the Special Issue Research Progress of New Tuberculosis Vaccines and Vaccine Design)
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