Vaccines

47 pages, 3011 KB

Open AccessReview

Current Status and Challenges of Vaccine Development for Seasonal Human Coronaviruses

by Bin Zhang, Yaoming Liu, Tao Chen, Jintao Lai, Sen Liu, Xiaoqing Liu, Yiqiang Zhu, Haiyue Rao, Haojie Peng and Xiancai Ma

Vaccines 2025, 13(11), 1168; https://doi.org/10.3390/vaccines13111168 - 16 Nov 2025

Abstract

Seasonal human coronaviruses (HCoVs), including HCoV-229E, HCoV-NL63, HCoV-OC43, and HCoV-HKU1, circulate globally in an epidemic pattern and account for a substantial proportion of common cold cases, particularly in infants, the elderly, and immunocompromised individuals. Although clinical manifestations are typically mild, these HCoVs exhibit [...] Read more.

Seasonal human coronaviruses (HCoVs), including HCoV-229E, HCoV-NL63, HCoV-OC43, and HCoV-HKU1, circulate globally in an epidemic pattern and account for a substantial proportion of common cold cases, particularly in infants, the elderly, and immunocompromised individuals. Although clinical manifestations are typically mild, these HCoVs exhibit ongoing antigenic drift and have demonstrated the potential to cause severe diseases in certain populations, underscoring the importance of developing targeted and broad-spectrum vaccines. This review systematically examines the pathogenesis, epidemiology, genomic architecture, and major antigenic determinants of seasonal HCoVs, highlighting key differences in receptor usage and the roles of structural proteins in modulating viral tropism and host immunity. We summarize recent advances across various vaccine platforms, including inactivated, DNA, mRNA, subunit, viral-vectored, and virus-like particle (VLP) approaches, in the development of seasonal HCoV vaccines. We specifically summarize preclinical and clinical findings demonstrating variable cross-reactivity between SARS-CoV-2 and seasonal HCoV vaccines. Evidence indicates that cross-reactive humoral and cellular immune responses following SARS-CoV-2 infection or vaccination predominantly target conserved epitopes of structural proteins, supporting strategies that incorporate conserved regions to achieve broad-spectrum protection. Finally, we discuss current challenges in pathogenesis research and vaccine development for seasonal HCoVs. We propose future directions for the development of innovative pan-coronavirus vaccines that integrate both humoral and cellular antigens, aiming to protect vulnerable populations and mitigate future zoonotic spillover threats. Full article

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

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12 pages, 387 KB

Open AccessArticle

Immune Responses to SARS-CoV-2 Variants WT and XBB.1.9: Assessing Vulnerabilities and Preparedness

by Limor Kliker, Michal Mandelboim, Menucha Jurkowicz, Neta S. Zuckerman, Enosh Tomer, Yaniv Lustig, Lital Keinan-Boker, Victoria Indenbaum and Ravit Bassal

Vaccines 2025, 13(11), 1167; https://doi.org/10.3390/vaccines13111167 - 16 Nov 2025

Abstract

Objectives: The emergence of SARS-CoV-2 variants with enhanced immune evasion capabilities poses ongoing challenges for maintaining population-level immunity. This study aim to evaluate neutralizing antibody responses to the wild-type (WT) strain and the Omicron sublineage XBB.1.9 in the Israeli population using serum samples [...] Read more.

Objectives: The emergence of SARS-CoV-2 variants with enhanced immune evasion capabilities poses ongoing challenges for maintaining population-level immunity. This study aim to evaluate neutralizing antibody responses to the wild-type (WT) strain and the Omicron sublineage XBB.1.9 in the Israeli population using serum samples collected between August 2022 and January 2023, prior to widespread circulation of XBB.1.9. Methods: Pseudovirus-based microneutralization assays incorporating variant-specific spike proteins were employed to measure neutralizing geometric mean titers (GMTs) across subgroups categorized by age, gender, socioeconomic status, and geographic region. Results: Neutralizing titers against XBB.1.9 were significantly lower than those against WT across all demographic groups, with a 29-fold reduction in neutralization activity against XBB.1.9, underscoring the immune escape potential of XBB.1.9. For WT, older adults (≥65 years) exhibited higher titers than younger individuals (p < 0.01), whereas no significant age-related differences were observed for XBB.1.9 (p > 0.05). Regional disparities in WT immunity were identified, with higher titers in Northern Israel compared to Jerusalem and Southern regions. By contrast, XBB.1.9 neutralization showed no significant regional variation. Conclusions: These findings demonstrate substantially reduced neutralization of XBB.1.9 compared to WT and reveal disparities in WT immunity by age and region. The results emphasize the need for updated vaccines targeting immune-evasive variants and for tailored vaccination strategies to address regional and demographic gaps in protection. Full article

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

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12 pages, 376 KB

Open AccessArticle

Seroprevalence and Vaccination Determinants of Varicella Zoster Virus Among Pediatric and Adolescent Populations in Northern Lebanon

by Nourhan Farhat, Dima El Safadi, Jana Massoud and Sara Khalife

Vaccines 2025, 13(11), 1166; https://doi.org/10.3390/vaccines13111166 - 15 Nov 2025

Abstract

Background: Varicella zoster virus (VZV) remains a significant cause of pediatric morbidity in populations in Lebanon, yet comprehensive data on population immunity and vaccination uptake are limited. This study aimed to estimate VZV seroprevalence and identify factors associated with immunity and vaccine uptake [...] Read more.

Background: Varicella zoster virus (VZV) remains a significant cause of pediatric morbidity in populations in Lebanon, yet comprehensive data on population immunity and vaccination uptake are limited. This study aimed to estimate VZV seroprevalence and identify factors associated with immunity and vaccine uptake among children and adolescents in Northern Lebanon. Methods: A cross-sectional study was conducted among 180 participants aged 1–18 years recruited from urban and rural settings in North Lebanon. After receiving informed parental consent, sociodemographic and clinical information were collected via structured questionnaires. Anti-VZV IgG and IgM antibodies were measured using validated Enzyme-Linked Immunosorbent Assays (ELISA). Associations with seropositivity and vaccination uptake were analyzed using multivariable logistic regression. Results: IgG seroprevalence was 79.4% (95% CI: 72.7–85.1), indicating prior exposure or immunization, while IgM antibodies, reflecting recent infection, were detected in 5.0% (95% CI: 2.3–9.4) of participants. Among vaccinated participants, IgG seropositivity was 63.6% (95% CI: 43.5–83.7) in the one-dose group and 89.5% (95% CI: 83.0–96.0) in the two-dose group. Completing the two-dose regimen was significantly associated with a higher IgG seropositivity (OR = 0.110, 95% CI: 3.2–52.4, p = 0.002). Parental reporting of history of varicella showed high sensitivity (99.0%) and overall accuracy (90.8%) in predicting seropositivity. Primary vaccination barriers included preference for natural infection (67%), perceived non-necessity (19%), and cost (10%). Regular pediatric follow-up strongly predicted vaccination (OR = 15.239, p < 0.001), whereas low parental awareness was associated with decreased vaccine uptake (OR = 0.027, p = 0.015). Conclusions: Suboptimal VZV vaccination coverage and persistent susceptibility underscore the need to integrate varicella vaccination into Lebanon’s national immunization schedule. Targeted educational efforts and enhanced pediatric healthcare engagement are critical to increasing vaccine uptake and reducing disease burden. Full article

(This article belongs to the Special Issue Bacterial and Viral Infections: Current Challenges and Vaccine Innovations)

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16 pages, 274 KB

Open AccessArticle

Effectiveness of an Active Offer of Influenza Vaccination to Hospitalized Frail Patients

by Alessandra Fallucca, Davide Anzà, Claudio Costantino, Cristina Genovese, Giovanni Genovese, Caterina Elisabetta Rizzo, Tania Vitello, Luigi Zagra and Vincenzo Restivo

Vaccines 2025, 13(11), 1165; https://doi.org/10.3390/vaccines13111165 - 15 Nov 2025

Abstract

Background/Objectives: Following the COVID-19 pandemic, the influenza season returned to its typical pre-pandemic circulation patterns. The category of people most vulnerable to severe influenza was older adults, and frail individuals, confirming their central role as a priority group for vaccination. The objective [...] Read more.

Background/Objectives: Following the COVID-19 pandemic, the influenza season returned to its typical pre-pandemic circulation patterns. The category of people most vulnerable to severe influenza was older adults, and frail individuals, confirming their central role as a priority group for vaccination. The objective of this study was to evaluate the impact of an active influenza vaccination program in an area with low influenza vaccination rates and propensity to vaccine co-administration. Methods: People recruited were hospitalized frail individuals, patients over the age of 60, and those with chronic illnesses or comorbidities. It was administered a questionnaire to investigate adherence to influenza vaccination and the Health Action Process Approach was used to evaluate the propensity to co-administration. Results: A total of 418 hospitalized patients were enrolled in the study, of whom 58.4% (n = 244) received the influenza vaccine and 17.9% (n = 75) had a higher propensity to have co-administration of influenza and other recommended vaccines. The factors associated with influenza vaccination acceptance were received advice from hospital healthcare workers (aOR = 10.6 p < 0.001) and previous influenza vaccination (aOR = 18.1; p < 0.001). Propensity to vaccine co-administration was associated with a higher educational level (aOR = 4.21; p = 0.002), receiving vaccination advice from hospital healthcare workers (aOR = 2.80; p = 0.03), perceived positive outcome (aOR = 1.29; p = 0.02) and perceived self-efficacy (aOR = 1.48; p < 0.001). Conslusions: This study explored the impact on influenza vaccination coverage in implementing in hospital vaccination offer. The reliability of this strategy, together with the standard vaccination offer, could allow reaching the recommended vaccination coverage, particularly among at-risk people. Full article

(This article belongs to the Special Issue Factors Affecting and Strategies Enhancing the Willingness to Receive and Uptake of Seasonal Influenza Vaccination)

17 pages, 633 KB

Open AccessReview

Brief Comparison of Novel Influenza Vaccine Design Strategies

by Shiqi Chai, Chuantao Ye, Chao Fan and Hong Jiang

Vaccines 2025, 13(11), 1164; https://doi.org/10.3390/vaccines13111164 - 15 Nov 2025

Abstract

Influenza viruses remain a major global public health concern, causing significant morbidity and mortality annually despite widespread vaccination efforts. The limitations of current seasonal vaccines, including strain-specific efficacy and manufacturing delays, have accelerated the development of next-generation candidates aiming for universal protection. This [...] Read more.

Influenza viruses remain a major global public health concern, causing significant morbidity and mortality annually despite widespread vaccination efforts. The limitations of current seasonal vaccines, including strain-specific efficacy and manufacturing delays, have accelerated the development of next-generation candidates aiming for universal protection. This review comprehensively summarizes the recent progress in universal influenza vaccine research. We first outline the key conserved antigenic targets, such as the hemagglutinin (HA) stem, neuraminidase (NA), and matrix proteins (M2e, NP, and M1), which are crucial for eliciting broad cross-reactive immunity. We then delve into advanced antigen design strategies, including immunofocusing, multi-antigen combinations, computationally optimized broadly reactive antigens (COBRA), and nanoparticle-based platforms. Furthermore, we evaluate evolving vaccine delivery systems, from traditional inactivated and live-attenuated vaccines to modern mRNA and viral vector platforms, alongside the critical role of novel adjuvants in enhancing immune responses. The convergence of these disciplines—structural biology, computational design, and nanotechnology—is driving the field toward a transformative goal. We conclude that the successful development of a universal influenza vaccine will likely depend on the strategic integration of these innovative approaches to overcome existing immunological and logistical challenges, ultimately providing durable and broad-spectrum protection against diverse influenza virus strains. Full article

(This article belongs to the Special Issue The Recent Development of Influenza Vaccine: 2nd Edition)

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14 pages, 2116 KB

Open AccessArticle

Two-Year Follow-Up of Humoral and Cellular Immune Responses to SARS-CoV-2 in Healthcare Professionals

by Silvie Ostřížková, Jan Martinek, Denisa Budirská, Hana Zelená, Alena Kloudová, Eduard Ježo, Rastislav Maďar and Hana Tomášková

Vaccines 2025, 13(11), 1163; https://doi.org/10.3390/vaccines13111163 - 14 Nov 2025

Abstract

Background/Objectives: Following the global spread of SARS-CoV-2, there was an urgent need for vaccine development to support immune protection. This study aimed to evaluate the impact of active and hybrid immunity on the durability of immunoglobulin G (IgG), neutralizing antibodies, and cellular immune [...] Read more.

Background/Objectives: Following the global spread of SARS-CoV-2, there was an urgent need for vaccine development to support immune protection. This study aimed to evaluate the impact of active and hybrid immunity on the durability of immunoglobulin G (IgG), neutralizing antibodies, and cellular immune responses over a two-year period. Methods: This longitudinal study was conducted from February 2021 to December 2023 at the Public Health Institute in Ostrava, Czech Republic. Anti-S IgG was measured using ELISA (Euroimmun), neutralizing antibodies via an in-house virus neustralization test (VNT), and cellular immune response using the IGRA test (ELISA, Euroimmun). Participants also completed a questionnaire on demographics, COVID-19 history, symptoms, and vaccination. Statistical analysis included descriptive and non-parametric tests (Mann–Whitney U, Kruskal–Wallis) at a 5% significance level. Results: The cohort included 149 individuals, 97.3% of whom were vaccinated with Comirnaty (Pfizer/BioNTech). A total of 17% had confirmed infection prior to vaccination and showed up to two-fold higher neutralizing antibody levels (p < 0.001) within 2–6 weeks postvaccination. Postvaccination infection was reported in 35% of participants. Although antibody levels declined over the 2–100 week period, participants remained seropositive across all three parameters. Cellular immune response (interferon-γ) remained consistently high throughout follow-up. Conclusions: The study demonstrates long-term durability of IgG and neutralizing antibodies and confirms durable cellular immunity up to two years postvaccination. Hybrid immunity significantly enhanced neutralizing antibody levels, supporting its added value in protective immunity against SARS-CoV-2. Full article

(This article belongs to the Special Issue Humoral and Cellular Response After Vaccination)

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18 pages, 6383 KB

Open AccessArticle

Adjuvanted Recombinant Hemagglutinin Vaccine Provides Durable and Broad-Spectrum Immunogenicity in Mice

by Rui Yu, Yan Guo, Senyan Zhang, Yuanbao Ai, Rui Wei, Yan Li, Hang Chen, Shuyun Liu, Caixia Zhang, Yuanfeng Yao, Meng Lv, Yingying Li, Yulin Chen, Peng Zhou, Siting Tu, Meijuan Fu, Yongshun Su, Yu Lin, Min Yang, Yanbin Ding, Siyu Tian, Cai Jing, Hang Chen, Tao Ma, Chunping Deng, Yu Zhou, Yuanyuan Li and Jing Jin Show full author list Hide full author list

Vaccines 2025, 13(11), 1162; https://doi.org/10.3390/vaccines13111162 - 14 Nov 2025

Abstract

Background: Seasonal influenza vaccines must be reformulated annually due to the high genetic variability and antigenic drift of circulating influenza viruses. The annual update, guided by World Health Organization (WHO) recommendations, results in significant challenges, including compressed production time periods, elevated manufacturing [...] Read more.

Background: Seasonal influenza vaccines must be reformulated annually due to the high genetic variability and antigenic drift of circulating influenza viruses. The annual update, guided by World Health Organization (WHO) recommendations, results in significant challenges, including compressed production time periods, elevated manufacturing costs, and global distribution pressures. Moreover, mismatches between vaccine strains and circulating viruses can severely reduce protective efficacy, underscoring the urgent need for broadly protective and long-lasting influenza vaccines. Methods: In this study, we developed an adjuvanted trivalent recombinant influenza virus-like particle vaccine (a-RIV) using the baculovirus–insect cell expression system and formulated it with an AS01-like adjuvant. The vaccine comprises full-length hemagglutinin (HA) proteins from WHO-recommended seasonal influenza strains: A/H1N1 (AH1), A/H3N2 (AH3), and B/Victoria (B/vic) lineages. The purified HA proteins were subsequently formulated with a liposomal adjuvant to enhance the immunogenicity. Results: In mouse immunization studies, the a-RIV vaccine elicited significantly stronger humoral and cellular immune responses than the licensed recombinant vaccine Flublok and the conventional inactivated influenza vaccine (IIV). High levels of functional anti-HA antibodies and antigen-specific T cell responses persisted for at least six months post-vaccination. Moreover, a-RIV induced broadly reactive antibodies capable of cross-binding to heterologous AH1 and AH3 influenza strains. Conclusions: Our data demonstrate that the a-RIV elicits enhanced, durable, and broadly cross-reactive immune responses against multiple influenza subtypes. These findings support the potential of adjuvanted recombinant HA-based vaccine as a promising candidate for the development of next-generation influenza vaccine. Full article

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

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14 pages, 955 KB

Open AccessBrief Report

Evaluating the Immune Response in Rabbits to an Escalating Dose of mRNA-Based HIV-1 Env Immunogens

by Shamim Ahmed, Durgadevi Parthasarathy, Tashina C. Picard, Gary R. Matyas, Mangala Rao and Alon Herschhorn

Vaccines 2025, 13(11), 1161; https://doi.org/10.3390/vaccines13111161 - 14 Nov 2025

Abstract

Background: The development of an effective HIV-1 vaccine remains a major challenge due to HIV-1’s extraordinary diversity, high mutation rate, and the rarity of broadly neutralizing antibody (bnAb) precursors. To address these challenges, we have previously immunized rabbits with mRNA-LNPs encoding for HIV-1 [...] Read more.

Background: The development of an effective HIV-1 vaccine remains a major challenge due to HIV-1’s extraordinary diversity, high mutation rate, and the rarity of broadly neutralizing antibody (bnAb) precursors. To address these challenges, we have previously immunized rabbits with mRNA-LNPs encoding for HIV-1 envelope glycoproteins (Envs), together with mRNA-LNPs encoding for HIV-1 Gag, which likely mediated the generation of virus-like particles presenting HIV-1 Envs to the immune system in vivo. Methods: Here, we investigated whether an escalating dose (ED) immunization using mRNA-LNP priming, followed by boosts with synthetic, protein-based, virus-like particles (synVLPs) displaying HIV-1 SOSIP trimers via SpyTag/SpyCatcher conjugation (group 1), could improve the quality and durability of the antibody responses compared to conventional bolus immunization (group 2). Previous studies have shown that, in contrast to single bolus immunization, the ED priming strategy could enhance B cell activation and prolong affinity maturation, resulting in higher-quality antibody responses. Results: Upon vaccination, rabbits from both groups developed strong homologous anti-Env antibody responses, with an increasing ability of sera from immunized rabbits to bind Envs following subsequent boosts. Antibodies in rabbit sera bound heterologous Envs, but there was no statistically significant difference in binding between the two groups. Overall, antibody responses were comparable across all animals and declined similarly over time in both groups, indicating that neither the adjuvants nor the ED priming led to any marked differences within this small sample size. Neutralization activity against homologous tier-2 HIV-1_AD8 (mRNA prime) and tier-2 HIV-1₁₀₅₉ (protein boost) was generally low across both groups; however, a higher neutralization titer was observed for the ED group against HIV-1_AD8 following the final boost. One of the rabbits from the bolus group exhibited exceptionally high neutralization titers that correlated with elevated Env-specific binding against HIV-1₁₀₅₉. Conclusions: These results highlight the challenges in eliciting broad and potent neutralizing antibody (nAb) responses. Our findings underscore the need for the continued development and refinement of immunogen design and delivery strategies to guide the elicitation of nAb. Full article

(This article belongs to the Special Issue Advances in HIV Vaccine Development, 2nd Edition)

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18 pages, 1422 KB

Open AccessArticle

Sustaining Local Production of Influenza Vaccines: A Global Study of Enabling Factors Among Vaccine Manufacturers

by Christopher Chadwick, Claudia Nannei, Erin Sparrow, William Ampofo, Antoine Flahault and Seth Berkley

Vaccines 2025, 13(11), 1160; https://doi.org/10.3390/vaccines13111160 - 14 Nov 2025

Abstract

Background/Objectives: Local production is a global priority for increasing access to routine, outbreak, and pandemic vaccines and leads to a variety of direct and indirect benefits for countries. This study aimed to characterize the enabling environment for the sustainable production of influenza vaccines, [...] Read more.

Background/Objectives: Local production is a global priority for increasing access to routine, outbreak, and pandemic vaccines and leads to a variety of direct and indirect benefits for countries. This study aimed to characterize the enabling environment for the sustainable production of influenza vaccines, including for epidemic and pandemic preparedness. Methods: National/local vaccine manufacturers were surveyed to capture data on influenza vaccine market contributions, government support for local production, and involvement in national pandemic preparedness activities. Using a conceptual framework for sustainable local production of influenza vaccines for epidemic and pandemic preparedness, manufacturers described 41 global/regional, national, and institutional sustainability factors across policy, health system, research and development (R&D), and regulatory thematic domains. In addition to the survey, key findings from country-level sustainability assessments of vaccine production in Bangladesh, Brazil, Indonesia, Serbia, and Viet Nam were analyzed to complement survey results. Results: This study included 12 participants representing 11 manufacturers from 10 countries. Of the 11 manufacturers, six reported that their countries have policies that support local production, but most manufacturers reported benefiting from some level of direct or indirect support by the government. Manufacturers considered 40/41 factors as important for sustainable production of influenza vaccines, and among the four domains, influenza prevention and control policies, influenza burden data, quality management, and regulatory filing capacity ranked highly. Additionally, manufacturers ranked factors related to cohesive policies for local production promotion and business/strategic planning at the manufacturer level as the top sustainability factors. Conclusions: Manufacturers broadly agreed on the importance of cohesive policies, evidence-based public health priorities, robust R&D and manufacturing investments, and regulatory readiness, though perceptions varied across contexts and company characteristics. Sustainable local production of influenza vaccines should be driven by the alignment of policies, investments, and demand. Full article

(This article belongs to the Special Issue Pandemic Influenza Vaccination)

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13 pages, 1133 KB

Open AccessArticle

Evaluation of Cholera Toxin B Subunit as a Novel Carrier Protein for Polysaccharide Conjugate Vaccines

by Chathuranga Siriwardhana, Aakriti Bajracharya, Florence Seal, Anup Datta and Subhash Kapre

Vaccines 2025, 13(11), 1159; https://doi.org/10.3390/vaccines13111159 - 13 Nov 2025

Abstract

Background: The immunogenicity of polysaccharide conjugate vaccines is critically influenced by the choice of carrier protein, which promotes a T-cell-dependent immune response mechanism leading to strong antibody production. In this study, the cholera toxin B subunit (CTB), a non-toxic pentameric protein, was evaluated [...] Read more.

Background: The immunogenicity of polysaccharide conjugate vaccines is critically influenced by the choice of carrier protein, which promotes a T-cell-dependent immune response mechanism leading to strong antibody production. In this study, the cholera toxin B subunit (CTB), a non-toxic pentameric protein, was evaluated as a novel carrier protein for pneumococcal polysaccharide antigens. Methods: Recombinant CTB was produced in Escherichia coli and purified using scalable chromatographic methods. Pneumococcal polysaccharides from serotypes 7F, 22F, and 33F were chemically activated with CDAP and conjugated to CTB. Results: The resulting glycoconjugates were characterized by SEC-MALS, confirming successful conjugation, high molecular weights, consistent polysaccharide-to-protein ratios, and acceptable endotoxin levels. Immunogenicity was assessed in rabbits following immunization with alum-adjuvanted formulations. Results: Robust IgG responses were elicited by all CTB-based conjugates, with antibody levels found to be comparable to those induced by CRM197 conjugates, demonstrating the potential of CTB as a promising alternative for the next generation of conjugate vaccines. Full article

(This article belongs to the Section Vaccines, Clinical Advancement, and Associated Immunology)

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14 pages, 1397 KB

Open AccessArticle

Influenza Vaccination in the Elderly in Three Cities in China: Current Status and Influencing Factors Under Different Funding Policies

by Rina Su, Hongting Zhao, Xiaokun Yang, Ying Qin, Jiandong Zheng, Xinyi Liu, Xinwei Du and Zhibin Peng

Vaccines 2025, 13(11), 1158; https://doi.org/10.3390/vaccines13111158 - 12 Nov 2025

Abstract

Background: Influenza is a major health threat to the elderly in China. Despite this, influenza vaccination rates still remain low and vary across regions that have different funding policies. In this study, we compare the vaccination status and influencing factors among older [...] Read more.

Background: Influenza is a major health threat to the elderly in China. Despite this, influenza vaccination rates still remain low and vary across regions that have different funding policies. In this study, we compare the vaccination status and influencing factors among older adults under the free, partial reimbursement, and self-paid vaccination strategies. Methods: Three cities with free, partial reimbursement, and self-paid influenza vaccination policies were selected. A cross-sectional, anonymous survey was then conducted. A total of 2265 elderly individuals aged 60 years and above were recruited using probability proportionate to size sampling. A standardized questionnaire was used during face-to-face interviews to collect data regarding the influenza vaccination status and influencing factors. The statistical analyses included chi-square tests, a multivariate logistic regression, and random forest models. Results: Among the 2265 participants (free policy region: n = 426; partial reimbursement region: n = 633; self-paid region: n = 1206), vaccination rates during the 2023–2024 season were significantly higher in the free policy region (53.29%) than in the partial reimbursement (20.85%) and self-paid (13.60%) regions (p < 0.001). The intention to vaccinate for the 2024–2025 season was also highest in the free policy region (68.78%), followed by partial reimbursement (47.71%) and self-paid (37.15%) regions (p < 0.001). This result demonstrated the same trend as the vaccination behavior. Cues to action (e.g., healthcare worker or family member recommendations) positively influenced vaccinations across all of the regions. In the self-paid region, perceived barriers, such as vaccine cost and side effect concerns, significantly reduced both behaviors and the next-season intention to vaccinate. Healthcare worker recommendations were key positive factors, while misconceptions and costs were major barriers to vaccination. Conclusions: Vaccination rates varied significantly across regions with different influenza vaccine subsidy policies. The free policy region demonstrated the highest coverage rate, while the self-paid region exhibited the lowest, suggesting that financial policies are a key determinant of vaccination uptake. Furthermore, free vaccination policies were associated with improved influenza vaccine knowledge among the elderly. Analysis of other influencing factors revealed that healthcare workers’ recommendations played a crucial role across all policy regions, though their impact on current-season vaccination behavior and next-season vaccination intention differed by subsidy context. Further studies are needed to explore the best approaches for optimizing region-specific subsidy strategies for promoting influenza vaccination among the elderly in China. Full article

(This article belongs to the Section Epidemiology and Vaccination)

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13 pages, 379 KB

Open AccessArticle

Cost-Effectiveness Analysis of Universal Rotavirus Vaccination Schedules in Syria

by Mania Mershed, Razan Altarabishi, Rasha Mohamed, Lamia Abu ajaj, Dima Alrashee, Manar Kamel and Salah Al Awaidy

Vaccines 2025, 13(11), 1157; https://doi.org/10.3390/vaccines13111157 - 12 Nov 2025

Abstract

Background: Rotavirus (RV) continues to be the leading cause of acute gastroenteritis (AGE) globally among children under five. National RV vaccination efforts have lowered morbidity and mortality. Vaccination is a key public health tool to alleviate this substantial burden of RV in middle- [...] Read more.

Background: Rotavirus (RV) continues to be the leading cause of acute gastroenteritis (AGE) globally among children under five. National RV vaccination efforts have lowered morbidity and mortality. Vaccination is a key public health tool to alleviate this substantial burden of RV in middle- and low-income countries. In Syria, RV morbidity accounts for 27% of severe GE. We conducted a cost-effectiveness analysis of introducing rotavirus vaccinations (RVV) into Syria’s National Immunization Program. Methods: A decision tree model was developed to assess the cost-saving of two-dose rotavirus vaccinations (Rotarix^®) compared to no vaccination. A birth cohort of 573,944 newborns was simulated throughout a 5-year time frame to capture the near-term health and economic effects. The analysis adopted an incremental cost-saving approach, evaluating a hypothetical 2023 birth cohort from the government’s perspective. Outcomes included the cost per disability-adjusted life year (DALY) prevented and the cost per death averted. Model inputs were derived from local data, specifically including healthcare and vaccination costs and deaths attributable to RVGE, the scientific literature, and national/international databases. The incremental cost-effectiveness ratio (ICER) measures the cost of avoiding one disability-adjusted life year (DALY) adopted. Results: Over five years, the two-dose RV strategy would avert 77,500 RVGE cases, reduce outpatient visits by 59%, and reduce severe RV hospitalizations by 41%. The vaccination program would cost $21,817,918 USD and avert $3,239,907 USD in healthcare costs, resulting in a net cost of $18,578,011 USD. The incremental cost-effectiveness ratio (ICER) was $2098 USD per DALY averted, which is below three times Syria’s GDP per capita ($753.6 USD), indicating high cost-effectiveness according to WHO benchmarks. Conclusions: Introducing rotavirus vaccination is highly cost-saving and will result in a substantial reduction in healthcare burdens and lives lost. Policy planners must ensure its inclusion in the National Immunization Programs, ensuring sustainable financing and equitable access. Full article

(This article belongs to the Special Issue Childhood Immunization and Public Health)

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19 pages, 5627 KB

Open AccessSystematic Review

Immunogenicity of a 20-Valent Pneumococcal Conjugate Vaccine Versus a 13-Valent Vaccine in Infants: A Systematic Review and Meta-Analysis

by María-Dolores Pacheco-Haro, Sergio Núñez de Arenas-Arroyo, Valentina Díaz-Goñi, Elisa-Janeth Velasco-Lucio, Carol-Ingrid Castellares-González, Valeria Reynolds-Cortez, Adriana Simeón-Prieto, Elsa Ignateva and Vicente Martínez-Vizcaíno

Vaccines 2025, 13(11), 1156; https://doi.org/10.3390/vaccines13111156 - 12 Nov 2025

Abstract

Background/Objectives: The 20-valent pneumococcal conjugate vaccine (PCV20) was approved for use in children and infants on the basis of studies comparing its safety and immunogenicity with those of the 13-valent vaccine (PCV13). PCV20 offers expanded coverage of seven additional serotypes. This meta-analysis aimed [...] Read more.

Background/Objectives: The 20-valent pneumococcal conjugate vaccine (PCV20) was approved for use in children and infants on the basis of studies comparing its safety and immunogenicity with those of the 13-valent vaccine (PCV13). PCV20 offers expanded coverage of seven additional serotypes. This meta-analysis aimed to summarize the available evidence on the comparative immunogenicity between PCV20 and PCV13. Methods: A systematic search of the PubMed, Web of Science, Scopus, Cochrane, and ClinicalTrials.gov databases was conducted in September 2024. The following inclusion criteria were used: (i) design: randomized clinical trials; (ii) outcomes: studies that included immunogenicity outcomes; (iii) compared vaccines: any study directly comparing the immunogenicity of PCV20 and PCV13; and (iv) population: infant population <2 years of age. No language or temporal restrictions were applied in the study. A random-effects meta-analysis was conducted via the Hartung–Knapp–Sidik–Jonkman method, with subgroup analyses according to the serotype and vaccination schedule (3 + 1 and 2 + 1). We used the revised Cochrane risk of bias 2 tool (RoB 2.0) to assess the risk of bias. The following parameters of immunogenicity were estimated: (i) the pooled geometric mean ratio (GMR PCV20/PCV13) of serotype-specific pneumococcal anticapsular antibodies, (ii) the pooled difference (PCV20-PCV13) in the percentage (DP) of participants who achieved predefined antibody levels for each serotype, and (iii) the pooled geometric mean titres (GMTs) of serotype-specific opsonophagocytic activity (OPA) in PCV20 and PCV13, along with their 95% confidence intervals (95% CIs). Results: Four studies (4093 infants aged 42–180 days) that compared the PCV20 and PCV13 vaccines, published between 2021 and 2024, were included in this meta-analysis. The immunogenicity of both groups was compared one month after the primary series and one month after the booster dose. The pooled results indicated that PCV20 elicited lower immune responses for the 13 serotypes shared with PCV13, according to the GMR and OPA outcomes. For the DP outcome, no statistically significant differences were observed between the two groups. Immune responses were higher for the additional serotypes in the PCV20 group; however, these differences were not statistically significant for all serotypes. Conclusions: This meta-analysis offers an overview of the evidence on the comparative immunogenicity of PCV20 and PCV13. Although some outcomes indicate that PCV20 elicits lower immune responses for the 13 serotypes shared with PCV13, it provides immunity against seven additional serotypes associated with IPD. Further studies are warranted to strengthen the evidence base, and continuous IPD surveillance remains essential to monitor shifts in serotype prevalence, assess the impact of current and future vaccines, and guide vaccine policy recommendations. Full article

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

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15 pages, 1201 KB

Open AccessArticle

Preparation and Immunological Efficacy Evaluation of mRNA Vaccines Targeting the Spike Protein of Bovine Coronavirus

by Shuyue Liu, Zhen Gong, Ping Wang, Fu Chen, Xiulong Fu, Haoyu Fan, Yue Li, Xiangshu Han, Junli Chen, Lixue Zhang, Lijun Xue, Hangfei Bai, Shufan Liu, Lulu Huang, Wei Du, Ang Lin and Jun Xia

Vaccines 2025, 13(11), 1155; https://doi.org/10.3390/vaccines13111155 - 12 Nov 2025

Abstract

Objectives: Bovine coronaviruses (BCoV) are endemic worldwide, causing diarrhea, winter dysentery, and bovine respiratory disease in newborn calves. These lead to higher calf mortality, reduced growth of fattening cows, and lower milk production in adult cows, resulting in significant losses to the cattle [...] Read more.

Objectives: Bovine coronaviruses (BCoV) are endemic worldwide, causing diarrhea, winter dysentery, and bovine respiratory disease in newborn calves. These lead to higher calf mortality, reduced growth of fattening cows, and lower milk production in adult cows, resulting in significant losses to the cattle industry. Since commercial preventive drugs are not available in China, and existing treatments can only reduce the mortality of sick calves without fundamental control, the development of safe and effective vaccines is crucial. Methods: Two mRNA vaccines targeting the BCoV spiny receptor-binding domain (S-RBD) were prepared: XBS01 and XBS02. These two mRNAs, optimized for coding by AI and encapsulated in lipid nanoparticles (LNPs), were injected intramuscularly into mice (10 μg per mouse, twice, 2 weeks apart); a blank control group was not immunized. Serum antibodies, memory B/T cell activation and cytokine secretion were assessed by ELISA, flow cytometry and ELISpot. Results: Both vaccines induced humoral and cellular immunity:anti-S-RBD IgG titers were higher than those of the control group, and there was memory B-cell production and T-cell activation. XBS02 was superior to XBS01 in terms of peak antibody, memory B-cell frequency, T-cell activation rate, and IFN-γ/IL-2 secretion, and showed a stronger Th 1 response. Conclusions: Both BCoV S-RBD mRNA vaccines had good immunogenicity, with XBS02 providing better protection. This study supports the optimization and application of BCoV mRNA vaccines and accumulates data for mRNA technology in veterinary practice. Full article

(This article belongs to the Special Issue Vaccine and Vaccination in Veterinary Medicine)

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14 pages, 232 KB

Open AccessArticle

Active Surveillance of Adverse Events Following Influenza Immunization in Jiangsu Province, China: A 2019–2023 Retrospective Study

by Zhiguo Wang, Sufang Wu, Xun Li, Ran Hu, Jing Yu, Borong Xu, Yuanyuan Zhu and Poning Liu

Vaccines 2025, 13(11), 1154; https://doi.org/10.3390/vaccines13111154 - 11 Nov 2025

Abstract

Background: Influenza vaccines have been administered in Jiangsu Province. This study aimed to conduct a comprehensive retrospective analysis of influenza vaccine safety in the region from 2019 to 2023. Methods: Data were sourced from the Chinese National Adverse Events Following Immunization Information System [...] Read more.

Background: Influenza vaccines have been administered in Jiangsu Province. This study aimed to conduct a comprehensive retrospective analysis of influenza vaccine safety in the region from 2019 to 2023. Methods: Data were sourced from the Chinese National Adverse Events Following Immunization Information System (CNAEFIS) and Jiangsu Provincial Electronic Immunization Registries System (JSEIRS) systems. A comprehensive retrospective analysis was performed to calculate the incidence rates of adverse events following immunization (AEFI) and to identify potential safety signals through disproportionality analysis. Results: Out of 4,906,905 administered doses, 2080 AEFI cases were reported, yielding an overall incidence rate of 42.39 per 1,000,000 doses. Significantly higher rates were observed in children aged 6–35 months (71.03 per 1,000,000) and among recipients of trivalent vaccines (52.79 per 1,000,000) compared to quadrivalent vaccines (36.03 per 1,000,000). The vast majority of AEFIs were mild, common adverse reactions (94.47%, predominantly fever and local reactions), occurring predominantly within one day post-vaccination, while disproportionality analysis identified expected signals for common adverse reactions and rare local purulent infections. Conclusions: Overall, the findings affirm the vaccine’s favorable safety profile, align with pre-marketing data, and underscore the critical role of continuous post-marketing surveillance in maintaining public confidence and monitoring the safety of both established and new vaccine formulations. Full article

(This article belongs to the Section Influenza Virus Vaccines)

35 pages, 1508 KB

Open AccessArticle

Estimating the Global, Regional, and National Economic Costs of COVID-19 Vaccination During the COVID-19 Pandemic

by Yansheng Chen, Haonan Zhang, Chaofan Wang and Hai Fang

Vaccines 2025, 13(11), 1153; https://doi.org/10.3390/vaccines13111153 - 11 Nov 2025

Abstract

Background: The COVID-19 pandemic led to an unprecedented global health and economic crisis, and vaccination emerged as a critical intervention to control the spread of the virus and mitigate its impact on health systems and economies. Despite the rapid development and deployment of [...] Read more.

Background: The COVID-19 pandemic led to an unprecedented global health and economic crisis, and vaccination emerged as a critical intervention to control the spread of the virus and mitigate its impact on health systems and economies. Despite the rapid development and deployment of vaccines, the financial commitments required for these vaccination programs are substantial, necessitating a comprehensive understanding of the associated costs to inform future public health strategies and resource allocation. Method: This analysis estimates the global, regional, and national economic costs of COVID-19 vaccination across 234 countries and regions in the period 2020–2023, consisting of vaccine procurement costs and administration costs. Result: As of 31 December 2023, the global costs of COVID-19 vaccination programs were estimated at USD 246.2 billion, with vaccine procurement accounting for approximately USD 140.2 billion and administration costs totaling USD 96.4 billion. Globally, a cumulative total of 136.9 billion doses of COVID-19 vaccines had been administered. Factoring in an estimated wastage rate of 10%, it is projected that approximately 150.6 billion doses were used. On a global scale, the average number of vaccine doses administered per capita was estimated at 1.73. The mean cost per capita was USD 17.70 (95% CI: USD 15.84–19.56) for vaccine procurement and USD 12.16 (95% CI: USD 10.29–14.02) for administration, resulting in a total average cost of USD 29.85 (95% CI: USD 26.33–33.37) per capita. Significant disparities in costs were observed across income groups and regions. High-income countries incurred a notably higher average cost per capita of USD 76.90 (95% CI: USD 72.38–81.41) in contrast to low-income countries, where the per capita cost was USD 7.20 (95% CI: USD 5.38–9.02). For middle-income countries, the average per capita costs were USD 15.02 (95% CI: USD 10.64–19.40) in lower-middle-income countries and USD 28.21 (95% CI: USD 23.60–32.83) in upper-middle-income countries. Regionally, the Americas (AMR) reported the highest total cost at USD 70.8 billion, with an average per capita cost of USD 65.23 (95% CI: USD 56.18–74.28). The Western Pacific Region (WPR) followed with a total cost of USD 63.9 billion and an average per capita cost of USD 31.93 (95% CI: USD 20.35–43.51). Conversely, the African Region (AFR) had the lowest total spending at USD 10.8 billion and a per capita cost of USD 8.85 (95% CI: USD 5.34–12.37), reflecting both lower vaccine procurement and administration costs. The European Region (EUR) recorded a high average per capita cost of USD 53.36 (95% CI: USD 46.79–59.94), with procurement costs at USD 31.28 (95% CI: USD 27.41–35.14) and administration costs of USD 22.09 (95% CI: USD 19.31–24.87). Conclusions: The global rollout of COVID-19 vaccination revealed substantial variation in cost structures across income groups. Procurement costs imposed greater burdens on low- and lower-middle-income countries, whereas delivery and administration costs dominated in higher-income settings. These disparities highlight persistent fiscal inequities and emphasize the need for stronger international coordination and cost transparency to enhance equity, efficiency, and preparedness in future vaccination efforts. Full article

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

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18 pages, 1913 KB

Open AccessArticle

Primary and Booster COVID-19 Vaccination in Patients with Sjögren’s Disease: Data from the Longitudinal SAFER Cohort Study

by Maressa Barbosa Beloni Lirio, Ketty Lysie Libardi Lira Machado, Olindo Assis Martins-Filho, Samira Tatiyama Miyamoto, Yasmin Gurtler Pinheiro de Oliveira, Érica Vieira Serrano, José Geraldo Mill, Karina Rosemarie Lallemand Tapia, Lunara Baptista Ferreira, Juliana Ribeiro de Oliveira, Maria da Penha Gomes Gouvea, Laura Gonçalves Rodrigues Aguiar, Barbara Oliveira Souza, Vitor Alves Cruz, Ricardo Machado Xavier, Andréa Teixeira Carvalho, Viviane Angelina de Souza, Gilda Aparecida Ferreira, Odirlei André Monticielo, Edgard Torres dos Reis Neto, Emilia Inoue Sato, Gecilmara Salviato Pileggi and Valéria Valim Show full author list Hide full author list

Vaccines 2025, 13(11), 1152; https://doi.org/10.3390/vaccines13111152 - 11 Nov 2025

Abstract

Introduction: The COVID-19 pandemic posed additional challenges for this vulnerable population, such as Sjögren’s disease (SjD), underscoring the need for effective and safe vaccination strategies. Objective: To evaluate the immunogenicity and safety of COVID-19 vaccines in patients with SjD. Methods: This prospective, observational, [...] Read more.

Introduction: The COVID-19 pandemic posed additional challenges for this vulnerable population, such as Sjögren’s disease (SjD), underscoring the need for effective and safe vaccination strategies. Objective: To evaluate the immunogenicity and safety of COVID-19 vaccines in patients with SjD. Methods: This prospective, observational, longitudinal study included SjD patients from the SAFER cohort. Immunogenicity was assessed via anti-spike IgG (IgG-S) titers using chemiluminescence reported as geometric mean titers (GMT) and fold increase in GMT (FI-GMT). Disease activity was evaluated using the ESSDAI score. Adverse events and COVID-19 infections were also monitored. Assessments were conducted at four time points: pre-first dose (T1), pre-second dose (T2), pre-booster (T3), and four weeks post-booster (T4). Primary vaccination involved ChAdOx1 nCoV-19 or inactivated vaccine (CoronaVac), and boosters were either homologous (ChAdOx1 nCoV-19) or heterologous (BNT162b2). Results: Among 51 participants (mean age 46 years; 90% female), 41% had comorbidities and 27% (n = 14/51) were highly immunosuppressed. Among those 73% (n = 37/51) under low immunosuppression, n = 8/51 (13%) were not using any medication. At baseline, 11% (n = 4/35) showed moderate/high disease activity, which decreased to 6.5% (n = 2/31) at T4. Primary vaccination was ChAdOx1 in 94% (n = 48/51) and CoronaVac in 6% (n = 3/51); 73% (n = 37/51) received heterologous and 27% (n = 14/51) homologous boosters. COVID-19 infection post-booster occurred in 20% (n = 10/51). Seroconversion rates reached nearly 100% across all medication subgroups except for biologic users, who showed delayed but stable seroconversion by T4. IgG-S titers increased progressively through T4. Primary immunization induced an ascending GMT in both vaccine types. At T4, the GMT was significantly higher in the BNT162b2 group (2148.03 [1452.05–3155.84]; p < 0.001; 95% CI) than in the ChAdOx1 group (324.29 [107.92–974.48]; p < 0.001; 95% CI); the fold-increase in immune response was six times greater with BNT162b2 (5.98 [2.97–12.03]; p = 0.001; 95% CI). Seroconversion was 100% in the heterologous group versus 83% in the homologous group (p > 0.01). Those with prior infection showed significantly higher titers, particularly at T2 and T3 (p < 0.001 for T1–T3). Adverse events were mild and not statistically significant. Multivariate regression confirmed BNT162b2 as an independent factor for higher antibody titers. Conclusion: COVID-19 vaccination in patients with SjD was safe and induced high anti-spike antibody titers and seropositivity. Heterologous boosting, particularly with BNT162b2, demonstrated superior immunogenicity. No association was found between vaccination and SjD disease flares or worsening activity. Full article

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

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15 pages, 947 KB

Open AccessArticle

Correlation of HPV Status with Colposcopy and Cervical Biopsy Results Among Non-Vaccinated Women: Findings from a Tertiary Care Hospital in Kazakhstan

by Talshyn Ukybassova, Gulzhanat Aimagambetova, Kuralay Kongrtay, Kuat Kassymbek, Milan Terzic, Sanimkul Makhambetova, Makhabbat Galym and Nazira Kamzayeva

Vaccines 2025, 13(11), 1151; https://doi.org/10.3390/vaccines13111151 - 11 Nov 2025

Abstract

Background/Objectives: Cervical cancer is one of the most frequent malignancies among women in Kazakhstan, where human papillomavirus (HPV) vaccination was initiated in 2024. Despite the implementation of vaccination and cytology-based screening programs, diagnostic limitations remain, and local evidence linking HPV infection to [...] Read more.

Background/Objectives: Cervical cancer is one of the most frequent malignancies among women in Kazakhstan, where human papillomavirus (HPV) vaccination was initiated in 2024. Despite the implementation of vaccination and cytology-based screening programs, diagnostic limitations remain, and local evidence linking HPV infection to clinical outcomes is scarce. This study aimed to evaluate the correlation between HPV status, cervical cytology results, colposcopic impression, and biopsy results in a non-vaccinated female population. Methods: A cross-sectional study was conducted at the University Medical Center, Astana, between November 2024 and March 2025. A total of 396 women of reproductive age were enrolled. Cervical samples underwent liquid-based cytology and high-risk HPV testing with the RealBest assay. Colposcopy was performed following abnormal cervical cytology results, and colposcopy-guided biopsies were obtained where indicated. Sociodemographic characteristics were assessed, and associations between HPV genotype and clinical outcomes were analyzed using descriptive and inferential statistics. Results: HPV infection was detected in 140 women (35.4%). HPV-16 was the most common genotype (11.4%), followed by HPV-52 (6.6%) and HPV-33 (5.3%). Among 198 women evaluated by colposcopy, abnormal findings were observed in 72.2%, with HPV-16 showing a significant association with higher-grade abnormalities (p < 0.001). Biopsies were available for 40 participants: 12 had CIN I, 12 had CIN II, 10 had CIN III, and 4 had carcinoma in situ. HPV-16 was the only genotype significantly linked to CIN II/III lesions. Conclusions: HPV-16 was strongly associated with abnormal colposcopic findings and high-grade histology, underscoring its oncogenic importance. The prevalence of HPV-52 and HPV-33 further supports the need for HPV nonavalent vaccination. These findings highlight the importance of HPV-based screening, genotype-specific triage, and expanded vaccination to reduce cervical cancer incidence in Kazakhstan. Full article

(This article belongs to the Special Issue Recent Advances and Strategies for the Management of CIN and HPV Eradication Starategies for the Prevention of Uterine Cervical Cancer)

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18 pages, 1162 KB

Open AccessReview

Shaping Antitumor Immunity with Peptide Vaccines: Implications of Immune Modulation at the Vaccine Site

by Amrita Sarkar, Emily Pauline Rabinovich and Craig Lee Slingluff, Jr.

Vaccines 2025, 13(11), 1150; https://doi.org/10.3390/vaccines13111150 - 11 Nov 2025

Abstract

Cancer vaccines have emerged as a class of therapeutics designed to harness the immune system to stimulate durable anti-tumor responses with lower systemic toxicity than conventional therapies. Many platforms have been explored, including protein, peptide, DNA, RNA, and cell-based vaccines. Within this landscape, [...] Read more.

Cancer vaccines have emerged as a class of therapeutics designed to harness the immune system to stimulate durable anti-tumor responses with lower systemic toxicity than conventional therapies. Many platforms have been explored, including protein, peptide, DNA, RNA, and cell-based vaccines. Within this landscape, peptide vaccines remain a promising approach. Most clinical trials have examined peripheral immune responses and clinical outcomes, but there is growing interest in the vaccine site microenvironment (VSME) as a window to understand local immune activation and its implications for systemic immunity and tumor control. Studies of the VSME have investigated the effects of adjuvants, local immune cell dynamics, and their correlation with systemic responses and outcomes. Local adjuvants typically enhance immune cell infiltration, though there are concerns regarding VSME sequestration or dysfunction of immune cells, which could impact systemic efficacy. Repeated vaccination at a single site may improve antigen presentation and immune responses, but factors such as injection site location may be linked to variability in clinical outcomes. Current studies are limited by substantial variability in sampling, timing, and analyses used in VSME assessment. This limits the comparability of findings and broader inferences regarding the influence of vaccine site dynamics on therapeutic efficacy. Standardized VSME assessment as part of future vaccine trials may improve evaluation of immune responses and provide a more consistent surrogate for vaccine effectiveness. This refinement may inform optimal vaccine strategies and further support the development of next-generation cancer immunotherapies. Full article

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

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