Vaccines

14 pages, 4701 KB

Open AccessArticle

A QS21+ CpG-Adjuvanted Rabies Virus G Subunit Vaccine Elicits Superior Humoral and Moderate Cellular Immunity

by Han Cao, Hui Li, Wenzhi Liu, Ning Luan, Jingping Hu, Meijun Kong, Jie Song and Cunbao Liu

Vaccines 2025, 13(8), 887; https://doi.org/10.3390/vaccines13080887 - 21 Aug 2025

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Abstract

Background: Rabies remains a fatal zoonotic disease caused by rabies virus (RABV), posing substantial global health challenges. Current vaccine production faces challenges in manufacturing efficiency and cost-effectiveness. The RABV glycoprotein (RABV-G) serves as the key antigen for eliciting protective immunity. Methods: We developed [...] Read more.

Background: Rabies remains a fatal zoonotic disease caused by rabies virus (RABV), posing substantial global health challenges. Current vaccine production faces challenges in manufacturing efficiency and cost-effectiveness. The RABV glycoprotein (RABV-G) serves as the key antigen for eliciting protective immunity. Methods: We developed a novel QS21+CpG-adjuvanted RABV-G subunit vaccine and systematically compared its performance against three control formulations: mRNA vaccine composed of H270P-targeted mutation packaged in lipid nanoparticles (LNP), named LNP-mRNA-G-H270P, commercial inactivated vaccine, and alum-adjuvanted RABV-G subunit vaccine. Results: The result show that the G+QS21+CpG subunit vaccine elicited superior humoral immunity, as evidenced by significantly higher RABV-G-specific IgG titers and virus-neutralizing antibody responses compared to all other groups. The LNP-mRNA-G-H270P vaccine maintained its expected cellular immunity advantage, with the G+QS21+CpG group exhibiting moderately reduced but still significant levels of IFN-γ-secreting splenocytes and levels of IL-2 in the supernatant of spleen cells, as well as IFN-γ-producing CD4+ T cells. Both LNP-mRNA-G-H270P and G+QS21+CpG vaccine groups provided 100% protection against lethal challenge (50LD₅₀ RABV). Conclusions: These findings provide novel vaccine/adjuvant strategies for rabies while elucidating platform-specific immunogenicity patterns, offering critical insights for pathogens requiring balanced humoral/cellular immunity. Full article

(This article belongs to the Section Vaccine Design, Development, and Delivery)

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15 pages, 3372 KB

Open AccessArticle

Do Family Physicians’ Recommendations for Influenza and Pneumococcal Vaccines Impact the Elderly Aged ≥60 Years? A Cross-Sectional Study in Six Chinese Cities

by Yuxing Wang, Jianing Dai, Shuai Yuan, Ying Chen, Zhujiazi Zhang, Ling Zhu, Gang Liu, Qiang Zeng, Qian Qiu, Chunyu Luo, Rendan Deng and Lili You

Vaccines 2025, 13(8), 886; https://doi.org/10.3390/vaccines13080886 - 21 Aug 2025

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Abstract

Background: Influenza vaccine and pneumococcal vaccine are essential to protect the health of older adults. This study focuses on the impact of family physicians’ recommendations on influenza and pneumococcal vaccine uptake among urban Chinese older adults and makes recommendations for improving vaccination [...] Read more.

Background: Influenza vaccine and pneumococcal vaccine are essential to protect the health of older adults. This study focuses on the impact of family physicians’ recommendations on influenza and pneumococcal vaccine uptake among urban Chinese older adults and makes recommendations for improving vaccination rates. Methods: A cross-sectional survey on influenza vaccination and pneumonia vaccination was conducted in December 2024 in six cities in China among adults aged ≥60 years. Marginal effects as well as logistic regression models were adopted to measure the relationship between family physician recommendation and influenza vaccination and pneumonia vaccination. Results: The overall influenza vaccination rate was 34.05% and pneumococcal vaccination rate was 22.79%. City, educational level, monthly income, health status, and family physician vaccination recommendation had significant impacts on influenza and pneumococcal vaccination (p < 0.05). Among the investigated elderly population, 48.78% and 28.56% had received recommendations from family physicians regarding influenza and pneumococcal vaccination, respectively. Analysis of marginal effects models revealed that physicians’ recommendations were significantly able to boost influenza and pneumococcal vaccination rates by 26.3% (average marginal effect = 0.263, 95% CI = 0.249–0.277) and 23.7% (average marginal effect = 0.237, 95% CI = 0.225–0.248), respectively (p < 0.001). In the adjusted model, family physician recommendation, compared with no family physician recommendation, was also associated with vaccine policy, monthly income, and age in influenza vaccine and pneumococcal vaccine uptake. Conclusions: Older adults’ influenza and pneumococcal vaccination rates need to be improved. Family physicians’ recommendations show a more significant impact on older adults. Family physician recommendations had the greatest boosting effect on vaccination among individuals aged 70–79. Healthcare providers should adopt different vaccine recommendation strategies based on the characteristics of older adults. Full article

(This article belongs to the Section Vaccines and Public Health)

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14 pages, 995 KB

Open AccessArticle

A Phase II Random, Double-Blind, Placebo-Controlled Study of the Safety and Immunogenicity of a Recombinant G Protein-Based Respiratory Syncytial Virus Vaccine in Healthy Older Adults

by Lunan Zhang, Gan Zhao, Xin Cheng, Shuo Wang, Jiarong Wang, Xuefen Huai, Yu Xia, Yanling Xiao, Sulin Ren, Shijie Zhang, Qiao Wang and Bin Wang

Vaccines 2025, 13(8), 885; https://doi.org/10.3390/vaccines13080885 - 21 Aug 2025

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Abstract

Background: Respiratory syncytial virus (RSV) poses a significant global health threat, particularly to children and the elderly. While progress has been made in RSV vaccine development, gaps remain, especially in protecting the elderly population. BARS13, a recombinant non-glycosylated G protein-based RSV vaccine, [...] Read more.

Background: Respiratory syncytial virus (RSV) poses a significant global health threat, particularly to children and the elderly. While progress has been made in RSV vaccine development, gaps remain, especially in protecting the elderly population. BARS13, a recombinant non-glycosylated G protein-based RSV vaccine, has shown promise in preclinical and Phase 1 studies. This phase II trial sought to determine whether escalating doses of BARS13 could enhance immune responses while maintaining safety and tolerability in healthy older adults aged 60–80 years. Methods: This study employed a rigorous randomized, double-blind, placebo-controlled design involving 125 participants across two Australian centers. Participants were randomized in a 3:1 (vaccine–placebo) ratio for Cohorts 1–2 (30 active, 10 placebo each) and a 2:1 ratio for Cohort 3 (30 active, 15 placebo). Cohort 1 (low dose) received 10 µg rRSV-G + 10 µg CsA in one arm + a placebo in the other (Days 1 and 29); Cohort 2 (high dose) received 10 µg rRSV-G + 10 µg CsA in both arms (20 µg total per dose, Days 1 and 29); Cohort 3 (multi-dose) received the same dose as that of Cohort 2 but with a third dose on Day 57. The placebo groups received IM injections in both arms at matching timepoints. The primary endpoints included safety and tolerability assessments, while the secondary endpoints evaluated the RSV G protein-specific IgG antibody concentrations using enzyme-linked immunosorbent assays (ELISAs). Statistical analysis was performed on both the safety and immunogenicity populations. Results: BARS13 was well-tolerated across all cohorts, with no serious adverse events (SAEs) related to the vaccine. The most common adverse events were mild local reactions (pain and tenderness) and systemic reactions (headache and fatigue), which resolved within 24–48 h. Immunogenicity analysis demonstrated a dose-dependent increase in the RSV G protein-specific IgG geometric mean concentrations (GMCs). Cohort 3, which received multiple high-repeat dose administrations, showed the highest immune response, with the IgG GMC rising from 1195.4 IU/mL on Day 1 to 1681.5 IU/mL on Day 113. Response rates were also the highest in Cohort 3, with 86.2% of participants showing an increase in antibody levels by Day 29. Conclusions: BARS13 demonstrated a favorable safety profile and strong immunogenicity in elderly participants, with a clear dose-dependent antibody response. These results support further development of BARS13 as a potential RSV vaccine candidate for the elderly. Further studies are needed to evaluate the long-term efficacy and optimal dosing schedule. Full article

(This article belongs to the Special Issue Clinical Strategies to Improve Efficacy, Effectiveness, and Safety of Vaccination in Humans)

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11 pages, 280 KB

Open AccessArticle

Participation in a Voluntary Blood Donation Program as an Opportunity to Assess and Enhance Tetanus Immunity in Adult Blood Donors with an Outdated or Unknown Vaccination Status

by Katarzyna Tkaczyszyn, Małgorzata Szymczyk-Nużka and Leszek Szenborn

Vaccines 2025, 13(8), 884; https://doi.org/10.3390/vaccines13080884 - 21 Aug 2025

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Abstract

Background/Objectives: Booster vaccination coverage in the adult population in Poland remains insufficient. The objective of this study was to utilize the opportunity of a visit to the Regional Blood Transfusion Center in Wroclaw—associated with blood donation—as a means to remind individuals about the [...] Read more.

Background/Objectives: Booster vaccination coverage in the adult population in Poland remains insufficient. The objective of this study was to utilize the opportunity of a visit to the Regional Blood Transfusion Center in Wroclaw—associated with blood donation—as a means to remind individuals about the need for tetanus booster vaccination and to assess tetanus immunity in healthy adults (30–40 years after their last mandatory dose) who had not received booster immunizations. Materials and Methods: A total of 97 blood donors aged 50 to 64 years (median age: 54 years) were enrolled, of whom 78% were male. 1. Tetanus immunity was assessed by a single measurement of serum anti-tetanus IgG antibody concentration. 2. A questionnaire was used to collect data relevant to tetanus immune status. 3. Individuals with insufficient protection received a booster dose of the tetanus vaccine, and the post-vaccination serologic response was evaluated. Results: 1. In the study group, 10.3% of participants had no protective immunity against Clostridium tetani, while 5.2% exhibited uncertain protection. An additional 32% demonstrated antibody levels conferring only short-term protection. Satisfactory protection—defined as immunity lasting at least 3 years—or long-term protection (at least 5 years) was identified in 52.5% of patients. Although 72% of donors reported receiving mandatory childhood immunizations, only 5% could provide medical documentation. In this subgroup, a significantly higher geometric mean antibody concentration was observed (0.69 vs. 0.52 IU/mL; p = 0.04), and significantly fewer participants required immediate post-exposure prophylaxis (1/39 vs. 14/54; p = 0.003). 2. Among the 46 individuals eligible for a booster dose, 17 (37%) returned for vaccination. Of these, 16 (94%) achieved antibody titers consistent with long-term protection following a single vaccine dose. Conclusions: Tetanus immunity among adults is heterogeneous and difficult to predict due to the frequent lack of vaccination records and unreliable self-reported histories. A history of injury and associated surgical wound care involving injection often serves as the only indication of prior vaccination. A single booster dose is highly effective in eliciting a robust immune response in individuals vaccinated during childhood but lacking recent boosters. Rising vaccine hesitancy toward both mandatory and recommended immunizations in Poland negatively influences adult decisions regarding tetanus vaccination. Participation in voluntary blood donation programs presents a valuable opportunity for immunization education, immune status screening, and the implementation of effective catch-up vaccination strategies. Full article

(This article belongs to the Section Vaccines and Public Health)

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20 pages, 1744 KB

Open AccessArticle

Immunogenic and Protective Properties of mRNA Vaccine Encoding Hemagglutinin of Avian Influenza A/H5N8 Virus, Delivered by Lipid Nanoparticles and Needle-Free Jet Injection

by Vladimir A. Yakovlev, Victoria R. Litvinova, Nadezhda B. Rudometova, Mariya B. Borgoyakova, Elena V. Tigeeva, Ekaterina V. Starostina, Ksenia I. Ivanova, Andrei S. Gudymo, Natalia V. Danilchenko, Olga N. Perfilyeva, Kristina P. Makarova, Danil I. Vahitov, Boris N. Zaitsev, Elena V. Dmitrienko, Sergey V. Sharabrin, Svetlana I. Krasnikova, Lyubov A. Kisakova, Denis N. Kisakov, Tatiana N. Ilyicheva, Vasiliy Yu. Marchenko, Larisa I. Karpenko, Andrey P. Rudometov and Alexander A. Ilyichev Show full author list Hide full author list

Vaccines 2025, 13(8), 883; https://doi.org/10.3390/vaccines13080883 - 21 Aug 2025

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Abstract

Background/Objectives: The development of a vaccine against highly pathogenic avian influenza viruses subtype A/H5 is an urgent task due to concerns about its pandemic potential. Methods: In this study, we have developed an experimental mRNA vaccine, mRNA-H5, encoding a modified hemagglutinin trimer of influenza [...] Read more.

Background/Objectives: The development of a vaccine against highly pathogenic avian influenza viruses subtype A/H5 is an urgent task due to concerns about its pandemic potential. Methods: In this study, we have developed an experimental mRNA vaccine, mRNA-H5, encoding a modified hemagglutinin trimer of influenza virus A/turkey/Stavropol/320-01/2020 (H5N8). BALB/c mice were immunized with the mRNA-H5 vaccine using lipid nanoparticles (LNPs) and needle-free jet injection (JI). Subsequently, the immune response to vaccine was assessed using ELISA, microneutralization assay, and ICS methods, and a challenge study was conducted. Results: mRNA-H5 was shown to effectively stimulate specific humoral and T-cell immune responses. Moreover, mRNA-H5 delivered by LNPs and JI provided 100% protection of immunized mice against lethal challenge with homologous and heterologous strains of avian influenza virus (A/Astrakhan/3212/2020 (H5N8) and A/chicken/Magadan/14-7V/2022 (H5N1), respectively). Conclusions: The present results indicate that JI can be considered as an alternative to LNPs for mRNA delivery, and according to the literature, JI is safer than delivery using LNP. mRNA-H5 has potential as a vaccine against infection with highly pathogenic avian influenza A/H5 viruses with pandemic potential. Full article

(This article belongs to the Special Issue Influenza Virus Vaccines and Vaccination)

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30 pages, 1145 KB

Open AccessReview

Decrypting the Immune Symphony for RNA Vaccines

by Brian Weidensee and Itishri Sahu

Vaccines 2025, 13(8), 882; https://doi.org/10.3390/vaccines13080882 - 20 Aug 2025

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Abstract

Messenger RNA (mRNA) vaccine technology has revolutionized the field of immunization, offering a non-infectious, non-genome-integrating platform that addresses many limitations of traditional vaccine modalities. Recent advancements in chemical modifications, delivery systems, and manufacturing processes have enhanced the stability, efficacy, and safety of RNA-based [...] Read more.

Messenger RNA (mRNA) vaccine technology has revolutionized the field of immunization, offering a non-infectious, non-genome-integrating platform that addresses many limitations of traditional vaccine modalities. Recent advancements in chemical modifications, delivery systems, and manufacturing processes have enhanced the stability, efficacy, and safety of RNA-based therapeutics, expanding their application beyond infectious diseases to include genetic disorders, cancer, and rare diseases. Central to the success of RNA vaccines is their ability to orchestrate a finely tuned immune response, leveraging both innate and adaptive immunity to achieve robust and durable protection. This review synthesizes current knowledge on the immunological mechanisms underpinning RNA vaccine efficacy, with a focus on the roles of pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs) and RIG-I-like receptors (RLRs) in sensing exogenous RNA, the impact of RNA modifications and manufacturing impurities on innate immune activation, and the subsequent cytokine and chemokine milieu that shapes adaptive responses. We also discuss the dual role of lipid nanoparticle (LNP) delivery systems as both carriers and adjuvants, highlighting their contribution to the vaccine’s immunogenicity and reactogenicity profile. Understanding these complex immune interactions is critical for optimizing RNA vaccine design, minimizing adverse effects, and expanding their therapeutic potential. This review aims to provide a comprehensive overview of the immune symphony orchestrated by RNA vaccines and to identify key areas for future research to further refine and expand the utility of this transformative technology. Full article

(This article belongs to the Special Issue Evaluating the Immune Response to RNA Vaccine)

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22 pages, 2593 KB

Open AccessReview

Therapeutic Vaccines for Non-Communicable Diseases: Global Progress and China’s Deployment Pathways

by Yifan Huang, Xiaohang Lyu and Yiu-Wing Kam

Vaccines 2025, 13(8), 881; https://doi.org/10.3390/vaccines13080881 - 20 Aug 2025

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Abstract

Background: Non-communicable diseases (NCDs) have become a major threat to global public health, with the disease burden particularly severe in developing countries, China being one of them. The preventive and control effects of traditional treatment methods on NCDs are limited, and innovative strategies [...] Read more.

Background: Non-communicable diseases (NCDs) have become a major threat to global public health, with the disease burden particularly severe in developing countries, China being one of them. The preventive and control effects of traditional treatment methods on NCDs are limited, and innovative strategies are urgently needed. In recent years, vaccine technology has expanded from the field of infectious diseases to non-communicable diseases (NCDs). Therapeutic vaccines have shown the potential to intervene in chronic diseases through immunomodulation, but their research and development (R & D), as well as promotion, still face multiple challenges. Methods: This article systematically reviews the current development status of NCD vaccines worldwide and points out the imbalance in their matching with disease burden: current research focuses on the field of cancer, while there is a lack of targeted vaccines for high-burden diseases such as hypertension and chronic kidney disease; the progress of independent R & D in China lags behind, and there are implementation obstacles such as uneven distribution of medical resources between urban and rural areas and low public willingness to be vaccinated. Results: By analyzing the biological mechanisms of NCD vaccines and non-biological challenges, phased solutions are proposed: In the short term, focus on target discovery and improvement of vaccine accessibility. In the medium term, strengthen multi-center clinical trials and international technology sharing. In the long term, build a digital health monitoring system and a public–private partnership financing model. Conclusions: The breakthrough of NCD vaccines requires interdisciplinary collaboration and systematic policy support. Their successful application will reshape the paradigm of chronic disease prevention and control, providing a new path for global health equity. Full article

(This article belongs to the Special Issue Virus Pandemics and Vaccinations)

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29 pages, 1172 KB

Open AccessReview

Oncolytic Herpes Simplex Virus Therapy: Latest Advances, Core Challenges, and Future Outlook

by Yiyang Zheng, Yusheng Pei, Chunyan Dong, Jinghui Liang, Tong Cai, Yuan Zhang, Dejiang Tan, Junzhi Wang and Qing He

Vaccines 2025, 13(8), 880; https://doi.org/10.3390/vaccines13080880 - 20 Aug 2025

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Abstract

Oncolytic virus (OV) immunotherapy, particularly with oncolytic herpes simplex virus (oHSV), has become a promising new strategy in cancer treatment. This field has achieved significant clinical milestones, highlighted by the FDA approval of Talimogene laherparepvec (T-VEC) for melanoma in 2015 and the approval [...] Read more.

Oncolytic virus (OV) immunotherapy, particularly with oncolytic herpes simplex virus (oHSV), has become a promising new strategy in cancer treatment. This field has achieved significant clinical milestones, highlighted by the FDA approval of Talimogene laherparepvec (T-VEC) for melanoma in 2015 and the approval of Teserpaturev/G47Δ for malignant glioma in Japan in 2021. This review synthesizes the key preclinical and clinical advancements in oHSV therapy over the last decade, critically analyzing the core challenges in target selection, genetic modification, administration routes, and targeted delivery. Key findings indicate that arming oHSV with immunomodulatory transgenes, such as cytokines and antibodies, and combining it with immune checkpoint inhibitors are critical strategies for enhancing therapeutic efficacy. Future research will focus on precision engineering using CRISPR/Cas9, the development of novel delivery vehicles like nanoparticles and mesenchymal stem cells (MSCs), and biomarker-guided personalized medicine, aiming to provide safer and more effective solutions for refractory cancers. This review synthesizes oHSV advances and analyzes novel delivery and gene-editing strategies. Full article

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17 pages, 3359 KB

Open AccessArticle

Development and Biological Properties of a New Live Attenuated Mumps Vaccine Strain

by Xue Song, Xiumei Ren, Yang Song, Shengbao Yang, Kailang Lu, Yan Zhang and Jiankai Liu

Vaccines 2025, 13(8), 879; https://doi.org/10.3390/vaccines13080879 - 20 Aug 2025

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Abstract

Background/Objectives: This study aimed to develop a new attenuated live mumps vaccine strain and determine its biological properties and effectiveness. Methods: Plaque purification and amplification were performed in chicken embryo cells. Candidate live attenuated mumps MuV-365 strain sequencing was performed. After [...] Read more.

Background/Objectives: This study aimed to develop a new attenuated live mumps vaccine strain and determine its biological properties and effectiveness. Methods: Plaque purification and amplification were performed in chicken embryo cells. Candidate live attenuated mumps MuV-365 strain sequencing was performed. After evaluating the potential neurotoxicity of the MuV-365 mumps strain, a preclinical safety evaluation of measles–mumps–rubella (MMR) live attenuated vaccine containing the MuV-365 strain was performed to support the registration and application of the MMR vaccine. Finally, mumps neutralization antibody titers and the concentration of anti-serum mumps-specific IgG were determined to evaluate the immunogenicity and efficacy of the MuV-365 strain and MMR vaccine in mice and rhesus monkeys. Results: The plaque of the PL-KUM main seed virus was screened, and strains whose sequences were highly homologous to RIT4385 (JL-5 derived) were selected to amplify. The candidate live attenuated mumps MuV-365 strain was then developed. Safety evaluation results indicated that the MuV-365 strain had no potential neurotoxicity, and the MMR vaccine containing the MuV-365 strain also showed no significant safety hazard. The immunogenicity of MuV-365 strain in BALB/c mice was not inferior to S79 and PL-KUM. After two doses of the MuV-365 strain, the concentration of anti-serum mumps-specific IgG of the MuV-365 strain was significantly higher than that of the S79 strain (p < 0.01). In rhesus monkeys, the MMR vaccine had good immunogenicity against measles and rubella after one dose, while immunogenicity against mumps improved after two doses. Conclusions: The developed MuV-365 strain was genetically stable, with adequate safety and immunogenicity. Full article

(This article belongs to the Special Issue Advancements in Vaccine Research: Epidemiology, Immunogenicity, Effectiveness and Safety)

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2 pages, 461 KB

Open AccessCorrection

Correction: Riccò et al. Respiratory Syncytial Virus: A WAidid Consensus Document on New Preventive Options. Vaccines 2024, 12, 1317

by Matteo Riccò, Bahaa Abu-Raya, Giancarlo Icardi, Vana Spoulou, David Greenberg, Oana Falup Pecurariu, Ivan Fan-Ngai Hung, Albert Osterhaus, Vittorio Sambri and Susanna Esposito

Vaccines 2025, 13(8), 878; https://doi.org/10.3390/vaccines13080878 - 20 Aug 2025

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Abstract

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

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39 pages, 6544 KB

Open AccessArticle

Trends in DTP3 Vaccination in Asia (2012–2023)

by Ines Aguinaga-Ontoso, Laura Guillen-Aguinaga, Sara Guillen-Aguinaga, Rosa Alas-Brun, Miriam Guillen-Aguinaga, Enrique Aguinaga-Ontoso, Luc Onambele and Francisco Guillen-Grima

Vaccines 2025, 13(8), 877; https://doi.org/10.3390/vaccines13080877 - 19 Aug 2025

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Abstract

Background/Objectives: DTP3 (diphtheria–tetanus–pertussis vaccine, third dose) coverage is a key indicator of the strength and continuity of routine immunization programs, which demonstrably reduces the burden of infectious diseases globally. This study aims to assess trends in DTP3 vaccination coverage across Asian regions and [...] Read more.

Background/Objectives: DTP3 (diphtheria–tetanus–pertussis vaccine, third dose) coverage is a key indicator of the strength and continuity of routine immunization programs, which demonstrably reduces the burden of infectious diseases globally. This study aims to assess trends in DTP3 vaccination coverage across Asian regions and countries from 2012 to 2023, focusing on changes associated with the COVID-19 pandemic. Methods: DTP3 vaccination data were obtained from official WHO/UNICEF Estimates of National Immunization Coverage (WUENIC) and analyzed using Joinpoint regression to detect statistically significant changes in vaccination trends. Data were grouped by five Asian subregions based on the UN geoscheme (Central, Eastern, Southeastern, Southern, and Western Asia), and trends were weighted using birth cohort sizes. The presence of joinpoints and annual percentage changes (APCs) was calculated, and potential pandemic-related disruptions were contextualized. Results: At the continental level, Asia experienced a modest 0.4% annual increase in DTP3 coverage between 2012 and 2023, with a significant joinpoint detected in 2018. Following this, Southeast Asia’s coverage declined at an annual rate of −4.32% before beginning to recover in 2021, while South Asia showed a similar pattern. Country-level analysis revealed significant heterogeneity, with a comparison between 2019 and 2023 showing profound post-pandemic declines in some nations, such as Lebanon (–21%) and Myanmar (–9.4%), while others, like Iraq and the Philippines, achieved substantial recoveries with coverage increasing by over 6 percentage points. These trends contrasted with persistent declines in fragile states (e.g., Afghanistan, Yemen) and sustained high coverage in others (e.g., Bangladesh, Israel). The pandemic, systemic weaknesses, emerging vaccine hesitancy, and misinformation were identified as key influences. Conclusions: There is progress in DTP3 coverage across Asia. There were pandemic-related disruptions, particularly in regions with fragile health systems. Strategies to address zero-dose and dropout children, improve service continuity, and counter misinformation are essential to meet immunization targets under the Immunization Agenda 2030. Full article

(This article belongs to the Special Issue Vaccination Strategies for Global Public Health)

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17 pages, 2429 KB

Open AccessArticle

BCG Vaccine-Induced Innate and Adaptive Pulmonary Immunity Correlating with Protective Efficacy Against Mycobacterium tuberculosis in the Lungs

by Mayank Khanna and Alistair J. Ramsay

Vaccines 2025, 13(8), 876; https://doi.org/10.3390/vaccines13080876 - 19 Aug 2025

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Abstract

Background/Objectives: Effective prophylaxis for Mycobacterium tuberculosis (Mtb) requires greater understanding of immune correlates of protection. With renewed interest in BCG as an Mtb vaccine, particularly via the intravenous (IV) route, our objective was to characterize both innate and adaptive immune correlates of vaccine-induced [...] Read more.

Background/Objectives: Effective prophylaxis for Mycobacterium tuberculosis (Mtb) requires greater understanding of immune correlates of protection. With renewed interest in BCG as an Mtb vaccine, particularly via the intravenous (IV) route, our objective was to characterize both innate and adaptive immune correlates of vaccine-induced pulmonary immunity as potential biomarkers for protective efficacy in a murine model of Mtb infection. Methods: Mice were given BCG via different routes and some boosted with recombinant virus constructs encoding Mtb Ag85B. Responding innate lymphoid cell (ILC) populations, T cells and B cells were analyzed by fluorescence activated cell sorting (FACS) for surface markers and by intracellular cytokine staining or antibody ELISPOT. Some immunized mice were challenged with aerosolized Mtb and monitored for bacterial growth in the lungs and spleen. Results: BCG given IV, but not intranasally or subcutaneously, resulted in marked increases in IFNγ expression at 72 h by pulmonary CD49⁺ NK cells, CD69⁺ ILC1, and two ILC3 populations, NCR-ILC3 and LTi cells, the latter also producing IL-22. Pulmonary ILC2 populations in these mice had significantly increased IL-13 expression at 24 h compared to the other routes. Interestingly, high levels of NK cells and ILC1 expressing IFNγ and/or TNFα were sustained at 8 wk, with sustained expression of IL-17A by pulmonary NCR-ILC3 and pronounced tissue-resident and effector memory CD4⁺ and CD8⁺ T cell responses. Intranasal boosting with Ad-Ag85B enhanced these T cell responses and generated Mtb-specific pulmonary IgA and IgG B cells, correlating with significantly reduced bacterial loads following Mtb challenge. Conclusions: BCG given IV primed for both early and persistent pulmonary ILC1/ILC3 responses of a predominantly Th1/Th17-type profile along with local Mtb-specific memory T cell and B cell populations, correlating with enhanced protective efficacy. These are worthy of further study as compartmentalized biomarkers for effective vaccine-induced local immunity against Mtb. Full article

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13 pages, 1016 KB

Open AccessArticle

Putting the Polio Workforce to Work in a Public Health Crisis: Contributions of the National Stop Transmission of Polio (NSTOP) Program to the COVID-19 Response in Pakistan

by Aslam Pervaiz, Rana Muhammad Safdar, Mumtaz Ali Laghari, Nadeem Shah, Amjad Mehmood, Kifayat Ullah, Richard Franka and Chukwuma Mbaeyi

Vaccines 2025, 13(8), 875; https://doi.org/10.3390/vaccines13080875 - 19 Aug 2025

Viewed by 450

Abstract

Background: Pakistan reported its first case of COVID-19 in February 2020 and joined other countries in activating a national emergency response following the declaration of the COVID-19 pandemic by the World Health Organization (WHO). Playing a vital role in the early phase [...] Read more.

Background: Pakistan reported its first case of COVID-19 in February 2020 and joined other countries in activating a national emergency response following the declaration of the COVID-19 pandemic by the World Health Organization (WHO). Playing a vital role in the early phase of the country’s response was the National Stop Transmission of Polio (NSTOP) program, a highly trained cadre of polio workers who ordinarily support polio eradication efforts in the country. Methods: We developed a reporting tool using Microsoft Excel that tracked the activities of NSTOP officers to support the COVID-19 response. All NSTOP officers submitted their activity reports fortnightly using this reporting tool. Each provincial NSTOP officer reviewed and compiled their respective officers’ reports and sent them to the federal NSTOP Team. We present a summary of the reports for the period from 1 March 2020 to 31 July 2020. Results: A total of 71 officers of the NSTOP program supported various aspects of Pakistan’s COVID-19 response, including coordination, detection and response activities, surveillance, quarantine/isolation management, training and orientation sessions for healthcare personnel, data analysis, community engagement, and risk communication. They successfully investigated 32,729 suspected COVID-19 cases, of which about one-third were confirmed cases, and facilitated the collection and dispatch of >57,000 samples from these cases. Conclusions: This report details NSTOP contributions to the early phase of the COVID-19 response in Pakistan, demonstrating the value of polio investments beyond eradicating the disease to encompass having a workforce that is ready to respond to emergent disease threats and outbreaks. Such a workforce could also play a role in strengthening the capacity of existing immunization systems to help improve routine vaccination coverage in resource-limited settings. Full article

(This article belongs to the Special Issue Vaccines and Vaccinations in the Pandemic Period)

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14 pages, 1644 KB

Open AccessArticle

Exploring TREC and KREC Levels in Nursing Home Residents and Staff and Their Association with SARS-CoV-2 Antibody Response After Vaccination

by Eline Meyers, Natalja Van Biesen, Liselore De Rop, Tine De Burghgraeve, Marina Digregorio, Laëtitia Buret, Samuel Coenen, Beatrice Scholtes, Jan Y. Verbakel, Stefan Heytens and Piet Cools

Vaccines 2025, 13(8), 874; https://doi.org/10.3390/vaccines13080874 - 19 Aug 2025

Viewed by 588

Abstract

Background: T-cell receptor excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs) are markers of recent thymic and bone marrow output, respectively. As they have previously been associated with immunosenescence, we aimed to investigate their association with anti-spike SARS-CoV-2 (S1RBD) IgG antibody response [...] Read more.

Background: T-cell receptor excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs) are markers of recent thymic and bone marrow output, respectively. As they have previously been associated with immunosenescence, we aimed to investigate their association with anti-spike SARS-CoV-2 (S1RBD) IgG antibody response after COVID-19 vaccination in nursing home residents (NHRs) and staff (NHS). Methods: We measured TREC and KREC levels and S1RBD IgG antibody levels from dried blood spots (DBSs) using in-house qPCRs and a commercial ELISA kit, respectively, in 200 participants (50 NHRs and 150 NHS). DBSs were collected in April 2021, approximately two months after primary course COVID-19 vaccination (BNT162b2). We assessed the association between TREC and KREC as dependent variables and age, sex, infection-priming status, and post-vaccination S1RBD-specific IgG concentrations as independent variables by simple and multiple linear regression. Results: TREC and KREC levels were significantly lower in NHRs compared with NHS and were negatively correlated with age (p < 0.001). Neither TREC nor KREC levels were significantly associated with SARS-CoV-2 antibody concentrations (p > 0.05). Conclusions: In our study population, TREC and KREC levels decreased with age and were statistically significantly lower in NHRs than NHS. They were, however, not associated with the antibody response after COVID-19 vaccination. Yet, additional research is warranted to explore their potential relevance in cellular immune responses or in combination with other biomarkers of immune function. Full article

(This article belongs to the Special Issue Understanding Immune Responses to COVID-19 Vaccines)

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10 pages, 578 KB

Open AccessArticle

IgG Antibodies to Pneumococcal Serotypes 1 and 5 in Relation to PCV13 Vaccination Status in Children Aged Under 5 Years in Lao PDR: A Cross-Sectional Survey

by Zheng Quan Toh, Ke Xin Tang, Keoudomphone Vilivong, Jana Lai, Toukta Bounkhoun, Valin Chanthaluanglath, Anisone Chanthongthip, Anne Balloch, Paul N. Newton, Audrey Dubot-Pérès, David A. B. Dance, Paul V. Licciardi and Fiona M. Russell

Vaccines 2025, 13(8), 873; https://doi.org/10.3390/vaccines13080873 - 18 Aug 2025

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Abstract

Background/Objectives: Pneumococcal serotypes 1 and 5 are associated with invasive pneumococcal disease (IPD). However, data on the circulation of these serotypes in Asia following the introduction of the pneumococcal conjugate vaccine (PCV) is limited. The Lao People’s Democratic Republic (Lao PDR) introduced PCV13 [...] Read more.

Background/Objectives: Pneumococcal serotypes 1 and 5 are associated with invasive pneumococcal disease (IPD). However, data on the circulation of these serotypes in Asia following the introduction of the pneumococcal conjugate vaccine (PCV) is limited. The Lao People’s Democratic Republic (Lao PDR) introduced PCV13 into its national immunisation programme in 2013. We undertook a serosurvey to assess the IgG responses to serotypes 1 and 5 from a convenience sample of children aged under 5 years in Vientiane, Lao PDR. Methods: This cross-sectional analysis used a convenience sample of the close contacts of children under five years old who had been hospitalised with acute respiratory infections between 2013 and 2016 in Vientiane, Lao PDR. Serotype-specific IgG concentrations to serotypes 1 and 5 were measured using a modified WHO ELISA method. Results: A total of 214 participants were included, 130 of whom were unvaccinated and 84 were vaccinated with PCV13. Compared to unvaccinated participants, a higher number of PCV-vaccinated participants met the IgG threshold for IPD (≥0.35 μg/mL) [41.5% (54/130) vs. 71.4% (60/84)] for serotype 1. In contrast, for serotype 5, a similar number of participants in the PCV-vaccinated and unvaccinated group met the IgG threshold for IPD (85.7% (72/84) vs. 82.3% (107/130). Among unvaccinated children, serotype 1 IgG levels peaked at 12 and 23 months at 0.49 µg/mL (95% CIs: 0.25–0.96), while serotype 5 IgG levels were similar across age groups, ranging from 0.55 to 0.79 µg/mL. Conclusions: Our findings indicate the considerable circulation of serotypes 1 and 5 within the community in Lao PDR. Ongoing surveillance is important for informing PCV vaccination strategies. Full article

(This article belongs to the Special Issue Host Immunity and Vaccines for Respiratory Pathogens)

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14 pages, 1955 KB

Open AccessArticle

Protective Efficacy of Subunit Vaccine Expressing Rv0976c Against Tuberculosis

by Ziwei Zhou, Dan Chen, Fuzeng Chen, Wenxi Xu, Zhifen Pan, Zhihao Xiang, Xiaoxiao Gao, Yeyu Li, Fagang Zhong, Jun Liu and Lu Zhang

Vaccines 2025, 13(8), 872; https://doi.org/10.3390/vaccines13080872 - 17 Aug 2025

Viewed by 602

Abstract

Objectives: The construction of subunit vaccines based on antigens that can induce strong cellular immunity is a widely accepted strategy to develop new tuberculosis vaccines. This study screens immunogens with potential for subunit vaccine development from seven candidate antigens and then verifies their [...] Read more.

Objectives: The construction of subunit vaccines based on antigens that can induce strong cellular immunity is a widely accepted strategy to develop new tuberculosis vaccines. This study screens immunogens with potential for subunit vaccine development from seven candidate antigens and then verifies their vaccine efficacy. Design: C57BL/6 mice were immunized subcutaneously with purified PPE19, PPE50, FadD21, Rv1505c, Rv1506c, Rv2035, and Rv0976c proteins formulated with Freund’s adjuvant to evaluate both the antigen-specific Th1 cellular immune responses and IgG level. After the vaccination of mice with recombined pcDNA3.1 expressing Rv0976c, intravenous or aerosol infection with M. tb were further challenged to assess protective efficacy. Results: Purified PPE19, PPE50, FadD21, and Rv0976c proteins generated strong antigen-specific Th1 cellular immune responses in mice. Compared to Ag85A, Rv0976c also stimulated higher IgG antibody level in mice. In particular, Rv0976c stimulated high and specific IgG antibody levels in serum from TB patients. The vaccination of mice with DNA vaccines expressing Rv0976c, followed by intravenous challenge with Bacillus Calmette–Guerin (BCG) Pasteur or M. tb, resulted in significant levels of protection that are comparable to or better than that afforded by the two leading antigens, Ag85A and PPE18. Conclusions: These results indicated that Rv0976c was a better protective antigen. Future studies to combine Rv0976c with other antigens and evaluate its effectiveness as a booster of BCG or as a therapeutic vaccine are warranted. Full article

(This article belongs to the Section Vaccines and Public Health)

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16 pages, 1000 KB

Open AccessArticle

Immune Response to Childhood Vaccination in Vertically Infected People Living with HIV: A Long-Term Evaluation

by Annachiara Zin, Elisa Barbieri, Giulia Brigadoi, Andrea Berlese, Lorenzo Chiusaroli, Daniele Mengato, Andrea Francavilla, Carlo Giaquinto, Daniele Donà and Osvalda Rampon

Vaccines 2025, 13(8), 871; https://doi.org/10.3390/vaccines13080871 - 16 Aug 2025

Viewed by 559

Abstract

Background: Despite virological suppression through antiretroviral therapy (ART), people living with HIV (PLHIV) may exhibit inadequate immune responses to vaccination, placing them at continued risk for preventable infectious diseases. Evidence regarding the durability of vaccine-induced immunity in PLHIV with vertically acquired infection remains [...] Read more.

Background: Despite virological suppression through antiretroviral therapy (ART), people living with HIV (PLHIV) may exhibit inadequate immune responses to vaccination, placing them at continued risk for preventable infectious diseases. Evidence regarding the durability of vaccine-induced immunity in PLHIV with vertically acquired infection remains limited. Methods: We conducted a cross-sectional observational study to evaluate humoral immunity to routine childhood vaccines in a cohort of PLHIV with perinatally acquired infection. Antibody titers against diphtheria, tetanus, measles, mumps, rubella, varicella, and hepatitis B (HBV) were retrospectively assessed via serological testing and review of medical records. Seroprotection rates were analyzed at predefined intervals following the completion of the primary immunization schedule. Multivariate analysis was used to explore potential predictors of long-term immune response. Results: A total of 85 individuals were included. Two years after completing the primary vaccination series, seroprotection rates were as follows: diphtheria 71%, tetanus 79%, measles 79%, mumps 67%, rubella 87%, and varicella 54%. Five years post-vaccination, 50–70% of participants maintained protective antibody levels, declining further to 50–58% after ten years. By twenty years, protective immunity dropped below 30% for all antigens except rubella (47%). HBV vaccine responses were notably poor, with only 60%, 37%, 24%, and 7.5% retaining protective anti-HBs titers at 2, 5, 10, and 20 years post-immunization, respectively. Time elapsed since vaccination was the sole significant predictor of seroprotection across all vaccines. Conclusions: In this cohort of vertically infected PLHIV, vaccine-induced immunity was suboptimal and declined markedly over time compared to the general population. These findings highlight the need for tailored immunization strategies, including timely boosters and regular serological monitoring, to maintain long-term protection in this high-risk group. Full article

(This article belongs to the Special Issue Effectiveness and Safety of Vaccines in Special Populations)

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21 pages, 1183 KB

Open AccessReview

Exploring the Contextual Factors That Influence Polio Supplementary Immunisation Activities in the WHO African Region: A Rapid Review

by Abdu A. Adamu, Duduzile Ndwandwe, Modjirom Ndoutabe, Usman S. Adamu, Rabiu I. Jalo, Khalid Abubakar, Johnson Muluh Ticha, Samafilan A. Ainan, Messeret Shibeshi, Terna Nomhwange, Jamal A. Ahmed and Charles Shey Wiysonge

Vaccines 2025, 13(8), 870; https://doi.org/10.3390/vaccines13080870 - 16 Aug 2025

Viewed by 824

Abstract

Introduction: Polio supplementary immunisation activities (SIA) are implemented to rapidly increase vaccination coverage and interrupt the transmission of poliovirus in a specified geographical area. Polio SIA complements routine immunisation and is crucial for the eradication of the disease by increasing population immunity. [...] Read more.

Introduction: Polio supplementary immunisation activities (SIA) are implemented to rapidly increase vaccination coverage and interrupt the transmission of poliovirus in a specified geographical area. Polio SIA complements routine immunisation and is crucial for the eradication of the disease by increasing population immunity. However, several contextual factors (i.e., implementation determinants) can influence the success or failure of polio SIA implementation; as such, understanding their dynamics can enhance proactive planning for practice improvement. This study aimed to explore and map the contextual factors of polio SIA implementation in the African region using a critical systems thinking approach. Methods: A rapid review of published and grey literature was conducted. The search included the Global Polio Eradication Initiative library for programmatic reports and two databases (PubMed and Google Scholar). Data extraction was performed using a structured tool. Thematic analysis was performed to categorise the identified contextual factors according to the domains and constructs of the Consolidated Framework for Implementation Research (CFIR). Then, a causal loop diagram (CLD) was used to map the linkages between the identified factors. Results: A total of seventy-eight contextual factors across the five CFIR domains were identified: three for innovation, twenty for outer setting, sixteen for inner setting, twenty-six for individuals, and thirteen for the implementation process. A system map of all the factors using CLD revealed multiple contingent connections, with eleven reinforcing loops and four balancing loops. Conclusions: This study identified the multilevel nature of the contextual factors that influence polio SIA, including their dynamics. The integration of CLD and CFIR in this study offers critical insights into the potential feedback loops that exists between the contextual factors which can be used as leverage points for policy and practice improvements, including tailoring strategies to enhance polio campaign implementation effectiveness, especially with the expanded use of the novel Oral Polio Vaccine type 2 (nOPV2) across countries in the region. Full article

(This article belongs to the Section Vaccines and Public Health)

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25 pages, 1959 KB

Open AccessArticle

Knowledge and Attitudes of Parents of School-Aged Children Regarding Vaccinations, and an Analysis of Measles and Pertussis Vaccination Coverage Using the Example of the City of Radomsko in Central Poland

by Paweł Nowicki, Magdalena Górajska and Anna Garus-Pakowska

Vaccines 2025, 13(8), 869; https://doi.org/10.3390/vaccines13080869 - 16 Aug 2025

Viewed by 805

Abstract

Background: Vaccinations are crucial for preventing infectious diseases. Parental knowledge and attitudes significantly impact vaccination decisions. Methods: This study analyzed parental knowledge and opinions on childhood vaccinations (focus: measles, pertussis) and assessed vaccination coverage rates in Radomsko, Poland. A cross-sectional study [...] Read more.

Background: Vaccinations are crucial for preventing infectious diseases. Parental knowledge and attitudes significantly impact vaccination decisions. Methods: This study analyzed parental knowledge and opinions on childhood vaccinations (focus: measles, pertussis) and assessed vaccination coverage rates in Radomsko, Poland. A cross-sectional study (Jan–Mar 2025) combined the following: (1) parent questionnaires (children aged 6–11 years), including opinions based on the validated VAX scale and (2) analysis of official vaccination coverage data (sanitary inspection). Statistical analysis included descriptive statistics and logistic regression; results are presented as odds ratios (OR). Results: A total of 459 parents participated (mean age 38.9 years, 95% female, 67% Master’s-level education). Conclusions: Most correctly identified measles (92%) and pertussis (85%) vaccines as mandatory. Considerable confusion existed about newer mandatory vaccines and varicella (78% incorrectly thought mandatory). Analysis revealed the influence of both knowledge and opinions from the VAX scale on vaccination decisions. Higher parental education significantly increased vaccination adherence for pertussis (OR = 2.03; p < 0.001) and both diseases (OR = 1.83; p < 0.001). While general vaccination awareness was high (97%), detailed knowledge of Poland’s mandatory schedule was alarmingly low, especially for newer vaccines. Parental education level is a key determinant of both accurate knowledge and vaccination compliance. Targeted educational interventions are urgently needed to improve parental understanding and support public health goals. Full article

(This article belongs to the Section Vaccines and Public Health)

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20 pages, 3230 KB

Open AccessArticle

Modelling the Impact of Vaccination and Other Intervention Strategies on Asymptomatic and Symptomatic Tuberculosis Transmission and Control in Thailand

by Md Abdul Kuddus, Sazia Khatun Tithi and Thitiya Theparod

Vaccines 2025, 13(8), 868; https://doi.org/10.3390/vaccines13080868 - 15 Aug 2025

Viewed by 1117

Abstract

Background: Tuberculosis (TB) remains a major global health challenge, including in Thailand, where both asymptomatic and symptomatic cases sustain transmission. The disease burden increases treatment complexity and mortality, requiring integrated care and coordinated policies. Methods: We developed a deterministic compartmental model to examine [...] Read more.

Background: Tuberculosis (TB) remains a major global health challenge, including in Thailand, where both asymptomatic and symptomatic cases sustain transmission. The disease burden increases treatment complexity and mortality, requiring integrated care and coordinated policies. Methods: We developed a deterministic compartmental model to examine the transmission dynamics of TB in Thailand, incorporating both latent and active stages of infection, as well as vaccination coverage. The model was calibrated using national TB incidence data, and sensitivity analysis revealed that the TB transmission rate was the most influential parameter affecting the basic reproduction number (R₀). We evaluated the impact of several intervention strategies, including increased treatment coverage for latent and active TB infections and improved vaccination rates. Results: Our analysis indicates that among the single interventions, scaling up effective treatment for latent TB infections produced the greatest reduction in asymptomatic and symptomatic cases, while enhanced treatment for active TB cases was second most effective for reducing both asymptomatic and symptomatic cases. Importantly, our results indicate that combining multiple interventions yields significantly greater reductions in overall TB incidence than any single approach alone. Our findings suggest that a modest investment in integrated TB control can substantially reduce TB transmission and disease burden in Thailand. However, complete eradication of TB would require a comprehensive and sustained investment to achieve near-universal coverage of both preventive and curative strategies. Conclusions: TB remains a significant public health threat in Thailand. Targeted interventions and integrated strategies are key to reducing disease burden and improving treatment outcomes. Full article

(This article belongs to the Section Vaccines and Public Health)

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22 pages, 10265 KB

Open AccessArticle

Long-Term Protection Against Symptomatic Omicron Infections Requires Balanced Immunity Against Spike Epitopes After COVID-19 Vaccination

by Heiko Pfister, Carsten Uhlig, Zsuzsanna Mayer, Eleni Polatoglou, Hannah Randeu, Silke Burglechner-Praun, Tabea Berchtold, Susanne Sernetz, Felicitas Heitzer, Andrea Strötges-Achatz, Ludwig Deml, Michaela Sander and Stefan Holdenrieder

Vaccines 2025, 13(8), 867; https://doi.org/10.3390/vaccines13080867 - 15 Aug 2025

Viewed by 692

Abstract

Background: Systematic studies providing differentiated insight into the contribution of immunity directed against conserved and non-conserved epitopes of SARS-CoV-2 Spike on long-term protection are rare and insufficiently guide future pan-variant vaccine research. The present observational cohort study aimed to evaluate the correlation [...] Read more.

Background: Systematic studies providing differentiated insight into the contribution of immunity directed against conserved and non-conserved epitopes of SARS-CoV-2 Spike on long-term protection are rare and insufficiently guide future pan-variant vaccine research. The present observational cohort study aimed to evaluate the correlation of neutralizing antibody levels and cellular immunity against the Spike protein with symptomatic Omicron breakthrough infection. Methods: Neutralizing antibody levels against multiple (sub)variants were analyzed 6 months following the second wild-type mRNA vaccination and 6 months after booster in 107 subjects using a multiplex surrogate virus neutralization assay. To assess cellular immunity, cytokine mRNA expression levels were determined after peptide pool stimulation in whole blood samples of a study subgroup. Results: Neutralizing antibody titers were found to serve as a reasonably reliable correlate of protection prior to booster immunization. However, the predictive power of neutralizing antibody titers was diminished after boosting. This loss appears to be due to a critical remodeling of the antibody repertoire—a process that was dose-dependent on pre-boost humoral immunity. Vaccination against Omicron infection was most effective when a balanced immune response to both conserved and non-conserved epitopes of the viral Spike protein was induced. While neutralizing antibodies against receptor-binding domain epitopes affected by mutations were specifically associated with protection from symptomatic variant infection, cellular immunity was most effective when targeting conserved Spike epitopes. Conclusions: Optimal long-term protection against Omicron infection requires balanced immunity to both conserved and non-conserved epitopes of the viral Spike protein. The limited availability of cross-neutralizing antibodies targeting non-conserved epitopes and their inherently lower efficacy renders them a limiting factor as humoral immunity wanes over time. Future pan-SARS-CoV-2 variant vaccines that primarily target conserved epitopes may therefore provide less effective long-term protection against symptomatic variant infection than vaccines targeting a broader epitope spectrum including both conserved and non-conserved epitopes. Full article

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

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14 pages, 926 KB

Open AccessArticle

Safety and Immunogenicity of a 23-Valent Pneumococcal Polysaccharide Vaccine (PPSV23) in Chinese Children, Adults and the Elderly: A Phase 4, Randomized, Double-Blind, Active-Controlled Clinical Trial

by Xiaoyu Liu, Gang Shi, Yuanyuan Dong, Wanqi Yang, Yinan Wang, Xianying Ye, Juxiang Zhang, Xinyi Yang, Dan Yu, Dan Song, Yuehong Ma, Zeng Wang, Hong Li and Weijun Hu

Vaccines 2025, 13(8), 866; https://doi.org/10.3390/vaccines13080866 - 15 Aug 2025

Viewed by 691

Abstract

Objectives: This randomized, double-blind, active-controlled non-inferiority phase 4 clinical trial was conducted to evaluate the immunogenicity and safety of a 23-valent pneumococcal polysaccharide vaccine (PPSV23) compared to an active comparator vaccine. Methods: Pneumococcal vaccine-naïve participants aged ≥2 years were randomly assigned in a [...] Read more.

Objectives: This randomized, double-blind, active-controlled non-inferiority phase 4 clinical trial was conducted to evaluate the immunogenicity and safety of a 23-valent pneumococcal polysaccharide vaccine (PPSV23) compared to an active comparator vaccine. Methods: Pneumococcal vaccine-naïve participants aged ≥2 years were randomly assigned in a 2:1 ratio to receive a single dose of either the investigational vaccine (n = 1199) or the comparator vaccine (n = 600). Immunogenicity was evaluated at baseline and 30 days post-vaccination by measuring serotype-specific IgG antibodies against all 23 pneumococcal serotypes using enzyme-linked immunosorbent assay. The primary outcome was seroconversion, defined as a ≥two-fold increase in serotype-specific IgG antibody titers at day 30 compared to baseline. Results: At one month post-vaccination, seroconversion rates for each of the 23 serotypes ranged from 59.22% to 95.67% in the treatment group, compared to 59.66% to 94.07% in the control group. Non-inferiority was demonstrated for all serotypes, with the lower bounds of the 95% confidence intervals (95%CI) for rate differences exceeding the predefined −10% margin. Moreover, superiority was observed for 12 serotypes (6B, 23F, 1, 2, 4, 8, 9N, 9V, 11A, 15B, 17F and 18C), as the lower bounds of their 95%CI for rate differences were above 0. Adverse reactions were reported in 236 (19.68%) participants of the investigational group and 118 (19.67%) of the control group within 30 days post-vaccination, with no significant differences between groups. Conclusions: The PPSV23 vaccine administered among individual aged ≥2 years was safe, well tolerated and immunogenic, eliciting an immune response either comparable to or higher than control vaccine. These findings support its use as a safe and effective option for pneumococcal immunization. Full article

(This article belongs to the Special Issue Safety and Immunogenicity of Vaccination)

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17 pages, 1623 KB

Open AccessArticle

Accelerating Neoantigen Discovery: A High-Throughput Approach to Immunogenic Target Identification

by Lena Pfitzer, Gitta Boons, Lien Lybaert, Wim van Criekinge, Cedric Bogaert and Bruno Fant

Vaccines 2025, 13(8), 865; https://doi.org/10.3390/vaccines13080865 - 15 Aug 2025

Viewed by 662

Abstract

Background: Antigen-targeting immunotherapies hinge on the accurate identification of immunogenic epitopes that elicit robust T-cell responses. However, current computational approaches focus primarily on MHC binding affinity, leading to high false-positive rates and limiting the clinical utility of antigen selection methods. Methods: [...] Read more.

Background: Antigen-targeting immunotherapies hinge on the accurate identification of immunogenic epitopes that elicit robust T-cell responses. However, current computational approaches focus primarily on MHC binding affinity, leading to high false-positive rates and limiting the clinical utility of antigen selection methods. Methods: We developed the neoIM (for “neoantigen immunogenicity”) model, a first-in-class, high-precision immunogenicity prediction tool that overcomes these limitations by focusing exclusively on overall CD8 T-cell response rather than MHC binding. neoIM, a random forest classifier, was trained solely on MHC-presented non-self peptides (n = 61.829). Its performance was assessed against that of currently existing alternatives on several in vitro immunogenicity datasets. In addition, its clinical impact was investigated in two retrospective analyses of clinical trial data by assessing the effect of neoIM-based antigen selection on the positive immunogenicity rate of personal vaccine designs. Finally, the potential for neoIM as a biomarker was investigated by assessing the correlation between neoIM scores and overall survival in a melanoma patient cohort treated with checkpoint inhibitors (CPI). Results: neoIM was found to substantially outperform publicly available tools in regards to in vitro benchmarks based on ELISpot assays, with an increase in predictive power of at least 30%, reducing false positives and improving target selection efficiency. In addition, using neoIM scores during patient-specific antigen prioritization and selection was shown to yield up to 50% more clinically actionable antigens for individual patients in two recent clinical trials. Finally, we showed that neoIM could further refine response prediction to checkpoint inhibition therapy, further demonstrating the importance of evaluating neoantigen immunogenicity. Conclusions: These findings establish neoIM as the first computational tool capable of accurately predicting epitope immunogenicity beyond MHC affinity. By enabling more precise target discovery and prioritization, neoIM has the potential to accelerate the development of next-generation antigen-based immunotherapies. Full article

(This article belongs to the Special Issue Tumor Vaccines: Current Processes, Prevailing Challenges and Future Perspectives)

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26 pages, 3208 KB

Open AccessArticle

Efficacy of Three Vaccine Regimens Against Infectious Hematopoietic Necrosis Virus Transmission Potential in Rainbow Trout

by Juliette Doumayrou, Mary G. Frazier, Hannah N. Brown and Andrew R. Wargo

Vaccines 2025, 13(8), 864; https://doi.org/10.3390/vaccines13080864 - 15 Aug 2025

Viewed by 676

Abstract

Background: Vaccination is often a highly effective approach for protecting against clinical disease and mortality caused by viruses. However, vaccine efficacy against viral transmission has rarely been assessed, which can provide vital information on the eradication efficacy and sustainability of vaccines in the [...] Read more.

Background: Vaccination is often a highly effective approach for protecting against clinical disease and mortality caused by viruses. However, vaccine efficacy against viral transmission has rarely been assessed, which can provide vital information on the eradication efficacy and sustainability of vaccines in the field. Methods: Here, we evaluated the host mortality, shedding, and direct fish-to-fish transmission protection efficacy of three vaccine regimens (DNA, inactivated, and attenuated) against infectious hematopoietic necrosis virus (IHNV) in rainbow trout. We quantified protection against single- and mixed-genotype IHNV infections when the vaccines were delivered by intramuscular injection, intraperitoneal injection, and bath immersion, respectively, to reflect field conditions. Results: All three vaccine regimens provided significant protection against fish mortality. The DNA vaccine regimen was qualitatively the most protective and the attenuated vaccine regimen the least. However, these three vaccines provided limited protection against viral shedding. Cumulative shedding over the course of the infection was only slightly reduced compared to unvaccinated fish. There was some indication that the viral genotype fish were exposed to influenced vaccine efficacy, perhaps as a result of genetic similarity to the vaccine strain. Likewise, the DNA vaccine reduced direct transmission in fish cohabitation experiments from 100% to 50%. The inactivated and attenuated vaccine had little impact on IHNV transmission. Conclusions: Collectively, our results suggest that existing IHNV vaccines that increase host survival provide minimal virus transmission protection in rainbow trout, which is likely to limit their long-term efficacy in the field. This work contributes to a growing body of evidence that enhancement of the transmission protection of IHNV and other vaccines will likely bolster disease reduction in the field. Full article

(This article belongs to the Section Veterinary Vaccines)

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25 pages, 376 KB

Open AccessReview

Research Progress of Universal Influenza Vaccine

by Liangliang Wang, Qian Xie, Pengju Yu, Jie Zhang, Chenchen He, Weijin Huang, Youchun Wang and Chenyan Zhao

Vaccines 2025, 13(8), 863; https://doi.org/10.3390/vaccines13080863 - 15 Aug 2025

Viewed by 1472

Abstract

Influenza viruses continue to undergo antigenic drift and shift, resulting in the need to update existing vaccines annually. Therefore, the development of a universal influenza vaccine has become an urgent global need. This paper reviews the functions of common antigenic targets of influenza [...] Read more.

Influenza viruses continue to undergo antigenic drift and shift, resulting in the need to update existing vaccines annually. Therefore, the development of a universal influenza vaccine has become an urgent global need. This paper reviews the functions of common antigenic targets of influenza vaccines and their advantages and disadvantages in universal vaccine design. We also summarize the common design strategies for universal influenza vaccines, which mainly include the immunofocusing strategy, multi-target combination strategy, T-cell strategy, computationally optimized broadly cross-reactive antigenic strategy (COBRA), and artificial intelligence strategy. In addition, we also sort out the latest research progress of universal influenza vaccines under different technological routes. This will help researchers better grasp the latest developments of universal influenza vaccines. Full article

(This article belongs to the Special Issue Influenza Virus Vaccines and Vaccination)

12 pages, 833 KB

Open AccessArticle

Efficacy of Heterologous Vaccination Using Virus-Like Particles and Vaccinia Virus Containing MIC8 and AMA1 Proteins of Toxoplasma gondii

by Hae-Ji Kang and Fu-Shi Quan

Vaccines 2025, 13(8), 862; https://doi.org/10.3390/vaccines13080862 - 15 Aug 2025

Viewed by 476

Abstract

Background: Toxoplasma gondii (T. gondii) infection causes serious diseases in immunocompromised patients and causes congenital toxoplasmosis in infants. T. gondii microneme protein 8 (MIC8) and apical membrane antigen 1 (AMA1) are essential proteins involved in parasitic invasion. Methods: In this [...] Read more.

Background: Toxoplasma gondii (T. gondii) infection causes serious diseases in immunocompromised patients and causes congenital toxoplasmosis in infants. T. gondii microneme protein 8 (MIC8) and apical membrane antigen 1 (AMA1) are essential proteins involved in parasitic invasion. Methods: In this study, we generated virus-like particles (VLPs) and recombinant vaccinia virus (rVV) containing MIC8 or AMA1 proteins. Vaccine efficacy was evaluated in mice (BALB/c) upon challenge infection with T. gondii ME49. Results: Intramuscular immunization with heterologous vaccines (rVV + VLPs; rVV for prime and VLPs for boost) elicited T. gondii-specific IgG antibody responses in mice. Four weeks after the boost, all mice were orally challenged with T. gondii ME49, and protective immunity was assessed. The responses of antibody-secreting cells for IgG2a and IgG2b and those of memory B cells and CD4+ and CD8+ T cells were higher in the rVV + VLP group than in the VLP + VLP group. The rVV + VLP group exhibited a significant reduction in cyst count in the brain. Conclusions: These findings indicate that heterologous vaccination with vaccinia viruses and VLPs improves vaccine efficacy. Full article

(This article belongs to the Special Issue Virus-Like Particle Vaccine Development)

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14 pages, 856 KB

Open AccessReview

Rural–Urban Disparities in COVID-19 Vaccine Uptake and Associated Mortality and Cardiovascular Disease Outcomes in the United States

by Bailey Smith, Fahad Farakh, Asma Hanif, Javed H Tunio and Shumaila Nida Javed Tunio

Vaccines 2025, 13(8), 861; https://doi.org/10.3390/vaccines13080861 - 14 Aug 2025

Viewed by 822

Abstract

Background: The COVID-19 pandemic magnified long-standing health disparities in the United States, particularly among rural, disadvantaged populations. These communities experience greater barriers to healthcare access, a higher prevalence of chronic illness, and increased vaccine hesitancy factors that collectively contribute to poorer health outcomes. [...] Read more.

Background: The COVID-19 pandemic magnified long-standing health disparities in the United States, particularly among rural, disadvantaged populations. These communities experience greater barriers to healthcare access, a higher prevalence of chronic illness, and increased vaccine hesitancy factors that collectively contribute to poorer health outcomes. Methods: This narrative review examines rural–urban disparities in COVID-19 vaccine uptake and their impact on mortality, with a focus on cardiovascular disease (CVD) outcomes. We synthesized the peer-reviewed literature, CDC data, and U.S. Census reports to assess factors contributing to vaccine hesitancy, vaccination coverage, COVID-19-related mortality, and CVD mortality trends. Results: Rural residents were less likely to initiate COVID-19 vaccination, showed greater vaccine hesitancy, and experienced higher rates of both COVID-19 and CVD mortality. These disparities were further driven by safety concerns surrounding mRNA technology, misinformation, infrastructural barriers, and sociodemographic factors including political affiliation, education, poverty, and religion. Notably, pre-existing CVD increased vulnerability to severe COVID-19 outcomes in rural communities. Conclusions: Expanding vaccination efforts and improving healthcare infrastructure are essential for addressing these widening health inequities. Future public health strategies should prioritize culturally tailored interventions and rural-specific outreach to reduce vaccine hesitancy and improve mortality outcomes in underserved populations. Full article

(This article belongs to the Special Issue COVID-19 Vaccination and Public Health: Addressing Global, Regional and Within-Country Inequalities)

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20 pages, 973 KB

Open AccessReview

New Vaccine Introduction in Middle-Income Countries Across the Middle East and North Africa—Progress and Challenges

by Chrissy Bishop, Deeksha Parashar, Diana Kizza, Motuma Abeshu, Miloud Kaddar, Abdallah Bchir, Atef El Maghraby, Hannah Schirrmacher, Zicheng Wang, Ulla Griffiths, Shahira Malm, Sowmya Kadandale and Saadia Farrukh

Vaccines 2025, 13(8), 860; https://doi.org/10.3390/vaccines13080860 - 14 Aug 2025

Viewed by 1297

Abstract

Background/Objectives: The middle-income countries (MICs) in the Middle East and North Africa (MENA) region face multifaceted challenges—including fiscal constraints, conflict, and vaccine hesitancy—that impede the timely introduction of critical vaccines. This study examines the status, barriers, and facilitators to introducing three critical [...] Read more.

Background/Objectives: The middle-income countries (MICs) in the Middle East and North Africa (MENA) region face multifaceted challenges—including fiscal constraints, conflict, and vaccine hesitancy—that impede the timely introduction of critical vaccines. This study examines the status, barriers, and facilitators to introducing three critical vaccines—human papillomavirus vaccine (HPV), pneumococcal conjugate vaccine (PCV), and rotavirus vaccine (RV)—across seven MENA MICs, to identify actionable solutions to enhance vaccine uptake and immunisation coverage. Methods: Using the READ methodology (ready materials, extract, analyse, and distil data), this review systematically analysed policy documents, reports, and the literature on the introduction of HPV, PCV, and RV vaccines in seven MENA MICs. A data extraction framework was designed to capture the status of vaccine introduction and barriers and facilitators to introduction. Findings and data gaps were validated with stakeholder consultations. Results: Of the seven study countries, progress in introducing PCV and RV has been uneven across the region (five countries have introduced PCV, four have introduced RV, and only a single country has introduced HPV at time of writing), hindered by vaccine hesitancy, fiscal challenges, and insufficient epidemiological data. Morocco is the only country to introduce all three vaccines, while Egypt has yet to introduce any. Other common barriers include the impact of conflict and displacement on healthcare infrastructure, delayed introduction due to the 2020 COVID-19 pandemic, and limited local production facilities and regional cooperation. In addition, not all countries eligible for Gavi MICs support have applied. These findings provide a roadmap for policymakers to accelerate equitable vaccine introduction in the MENA region. Conclusions: Targeted efforts, such as addressing fiscal constraints, improving local manufacturing, tackling gender barriers, and fostering public trust, paired with regional collaboration, can help bridge gaps and ensure no community is left behind in preventing vaccine-preventable diseases. Full article

(This article belongs to the Section Vaccines and Public Health)

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13 pages, 1290 KB

Open AccessSystematic Review

Immunogenicity as a Predictor of Influenza Vaccine Efficacy: A Systematic Review

by André Miguel Martins, Luis Félix Valero Juan, Marlene Santos and João P. Martins

Vaccines 2025, 13(8), 859; https://doi.org/10.3390/vaccines13080859 - 14 Aug 2025

Viewed by 653

Abstract

Background/Objectives: Influenza represents a significant burden on global public health, and vaccination is the most effective strategy to reduce it. The large investment in vaccination programs and the need for adjustments in vaccine serotypes are important reasons for evaluating the influenza vaccine’s efficacy [...] Read more.

Background/Objectives: Influenza represents a significant burden on global public health, and vaccination is the most effective strategy to reduce it. The large investment in vaccination programs and the need for adjustments in vaccine serotypes are important reasons for evaluating the influenza vaccine’s efficacy every year. Establishing a relationship between immunogenicity data and efficacy is also crucial for predicting the efficacy of a vaccine during its development. Antibody response measurement is one of the most common methods for evaluating immunogenicity, particularly in vaccines and biologics. The aim of this systematic review was to define a model that relates the immunogenicity of a given vaccine to its efficacy, based on hemagglutination inhibition titer levels. Methods: To achieve this goal, information was gathered from articles linking immunogenicity with the efficacy of the influenza vaccine in the Medline and Scopus databases. Different mathematical models were developed and applied to assess the relationship between HAI titers and the effectiveness of the flu vaccine. This analysis was conducted for the various existing vaccines, for the different influenza virus strains, and for their efficacy in paediatric populations. Results: The r² obtained ranged from 0.2579 to 0.966, which points to the importance of this immunological factor in the efficacy of the influenza vaccine. Conclusions: The efficacy values for titer level 40 confirm the validity of the data provided by Hobson. Full article

(This article belongs to the Special Issue Influenza Virus Vaccines and Vaccination)

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20 pages, 8252 KB

Open AccessArticle

Evaluation of Cross-Protection of African Swine Fever Vaccine ASFV-G-ΔI177L Between ASFV Biotypes

by Manuel V. Borca, Elizabeth Ramirez-Medina, Christine Mutisya, Rose Ojuok, Josiah Odaba, Mark Dihbol, Anna Lacasta and Douglas P. Gladue

Vaccines 2025, 13(8), 858; https://doi.org/10.3390/vaccines13080858 - 13 Aug 2025

Viewed by 910

Abstract

Background/Objectives: Vaccine development for the prevention of ASF has been very challenging due to the extensive genetic and largely unknown antigenic diversity. Inactivated vaccines, using different inactivation methods and a variety of adjuvants, have been consistently inefficacious. Historically, animals recovering from an infection [...] Read more.

Background/Objectives: Vaccine development for the prevention of ASF has been very challenging due to the extensive genetic and largely unknown antigenic diversity. Inactivated vaccines, using different inactivation methods and a variety of adjuvants, have been consistently inefficacious. Historically, animals recovering from an infection with an attenuated virus became protected from the development of a clinical disease caused by an antigenically related strain. Therefore, immunization of susceptible animals with attenuathe ted virus strains has become a common method of vaccination with the first two commercially available vaccines based on recombinant live-attenuated viruses (LAVs). An important limitation is that the efficacy of the LAV is restricted to those strains that are antigenically related and, in most cases, only provide protection against homologous strains. Due to the unknown antigenic heterogeneity among all ASFV field isolates, the development of broad-spectrum vaccines is a challenge. Besides the anecdotal data, there is not a large amount of information describing patterns of cross-protection between different ASFV strains. Methods: We evaluated the cross-protection induced by the ASFV live-attenuated vaccine ASFV-G-ΔI177L against different biotypes of ASFV and compared their genomic sequences to determine potential genetic mutations that could cause the lack of cross-protection. Results: Results presented here demonstrate different patterns of protection when ASFV-G-ΔI177L vaccinated pigs were challenged with six different ASFV field isolates belonging to different biotypes. Conclusions: The presence of cross-protection cannot be predicted solely by the classical methodology for genotyping-based B646L ORF only. Biotyping, considering the entire virus proteome, appears to be a more promising prediction tool, although additional gathering of experimental data will be necessary to fully validate it; until then, the presence of cross-protection needs to be confirmed in efficacy trials challenging vaccinated animals. Full article

(This article belongs to the Special Issue Swine Vaccines and Vaccination)

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Vaccines, Volume 13, Issue 8 (August 2025) – 112 articles

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