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Maternal Immunization: Current Evidence and Key Challenges
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Dengue Vaccine Development and Deployment into Routine Immunization
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Exploring the Challenges of Lipid Nanoparticle Development: The In Vitro–In Vivo Correlation Gap
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Safety and Efficacy of Vaccination During Lactation
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Immunogenicity of a Fast-Growing Hepatitis A Vaccine Candidate
Journal Description
Vaccines
Vaccines
is an international, peer-reviewed, open access journal published monthly online by MDPI.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, Embase, CAPlus / SciFinder, and other databases.
- Journal Rank: JCR - Q2 (Medicine, Research and Experimental) / CiteScore - Q1 (Pharmacology (medical))
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 19.6 days after submission; acceptance to publication is undertaken in 2.8 days (median values for papers published in this journal in the first half of 2025).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
Impact Factor:
3.4 (2024);
5-Year Impact Factor:
3.7 (2024)
Latest Articles
Vaccines and Vaccination: Feature Papers
Vaccines 2025, 13(7), 720; https://doi.org/10.3390/vaccines13070720 (registering DOI) - 1 Jul 2025
Abstract
This Special Issue, entitled “Vaccines and vaccination: Feature Papers”, included articles that addressed various issues related to vaccines and vaccination, including studies assessing interventions to increase vaccination coverage [...]
Full article
(This article belongs to the Special Issue Vaccines and Vaccination: Feature Papers)
Open AccessArticle
Enablers and Barriers of COVID-19 Vaccination in the Philippines
by
Evalyn Roxas, Paulyn Jean Acacio-Claro, Maria Margarita Lota, Alvin Abeleda, Soledad Natalia Dalisay, Madilene Landicho, Yoshiki Fujimori, Jan Zarlyn Rosuello, Jessica Kaufman, Margaret Danchin, Vicente Belizario, Jr. and Florian Vogt
Vaccines 2025, 13(7), 719; https://doi.org/10.3390/vaccines13070719 - 1 Jul 2025
Abstract
Background: The COVID-19 pandemic prompted extensive vaccination efforts globally, yet in the Philippines, many families remained unvaccinated. Caregivers are key decision-makers for family vaccination, but evidence on factors influencing their own vaccine uptake is limited. Methods: A cross-sectional survey of primary
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Background: The COVID-19 pandemic prompted extensive vaccination efforts globally, yet in the Philippines, many families remained unvaccinated. Caregivers are key decision-makers for family vaccination, but evidence on factors influencing their own vaccine uptake is limited. Methods: A cross-sectional survey of primary caregivers was conducted in low COVID-19 vaccine uptake regions in the Philippines from July to October 2023 using a validated questionnaire. Multivariable logistic regression identified enablers and barriers to vaccine uptake. Results: Among 775 respondents, 72.3% completed primary vaccination, 3.3% had incomplete vaccination, and 24.4% were unvaccinated. Key factors for vaccination included self, family, and community protection, and the influence of government regulations. Distrust in vaccine safety was the main barrier. Positive associations with vaccine uptake were found for age [30–45 years (aOR = 2.23) and 46–59 years (aOR = 2.84)], education [secondary (aOR = 2.25) and tertiary (aOR = 4.93)], and employment (aOR = 1.99). Confidence in vaccine safety (aOR = 1.92), vaccine effectiveness (aOR = 2.23), and satisfaction with vaccination efforts (aOR = 2.39) were additional enablers. Disagreement with restrictions on the unvaccinated was a barrier (aOR = 0.31). Conclusions: This study identified multiple factors influencing COVID-19 vaccination among primary caregivers in low uptake areas of the Philippines. Interventions addressing perceptions about vaccine safety and effectiveness, particularly among younger and less educated caregivers, may improve public trust and satisfaction with vaccination efforts.
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(This article belongs to the Special Issue Promoting Research, Development and Access to Vaccines to Address Global Inequities)
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Open AccessArticle
Pre-Vaccination Immune Profiles and Responsiveness to Innate Stimuli Predict Reactogenicity and Antibody Magnitude Following mRNA Vaccination
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Amanda E. Zelkoski, Emilie Goguet, Emily Samuels Darcey, Mohamad-Gabriel Alameh, Hooda Said, Simon Pollett, John H. Powers III, Eric D. Laing, Cara Olsen, Edward Mitre and Allison M. W. Malloy
Vaccines 2025, 13(7), 718; https://doi.org/10.3390/vaccines13070718 - 1 Jul 2025
Abstract
Background: While mRNA vaccines effectively limit hospitalization and severe COVID-19 disease, the precise early innate immune mechanisms associated with their efficacy and reactogenicity remain underexplored. The identification of innate immune correlates prior to vaccination could provide mechanistic insights and potentially predict responses. Methods:
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Background: While mRNA vaccines effectively limit hospitalization and severe COVID-19 disease, the precise early innate immune mechanisms associated with their efficacy and reactogenicity remain underexplored. The identification of innate immune correlates prior to vaccination could provide mechanistic insights and potentially predict responses. Methods: We developed an in vitro model to study the innate immune activation of pre-vaccination peripheral blood mononuclear cells (PBMCs) collected from participants enrolled in a well-characterized COVID-19 BioNTech/Pfizer BNT162b2 vaccine (BNT162b2 vaccine) cohort. Pre-vaccination PBMCs were stimulated with empty lipid nanoparticle (LNP), mRNA-LNP, or Toll-like receptor (TLR) agonists. Using multiparameter spectral flow cytometry, we analyzed the baseline immune state, innate responsiveness to stimuli, and cytokine profiles of study participants. These pre-vaccination in vitro results were analyzed for correlations with post-vaccination symptoms and spike-specific IgG responses. Results: Baseline dendritic cell (DC) states inversely correlated with the magnitude of symptoms following BNT162b2 vaccination. Heightened conventional (cDC) and weaker plasmacytoid DC (pDC) responses to RNA stimuli correlated with the magnitude of an acute IgG response. IgG durability modestly correlated with a lower pDC state but higher cDC2 and monocyte baseline states and inversely correlated with TLR3 agonist responsiveness. Conclusions: The pre-vaccination assessment of innate immune function and resting states can be used to fit models potentially predictive of immunogenicity and reactogenicity to BNT162b2 vaccination. Pre-vaccination DC states may influence reactogenicity, while the response to RNA may impact antibody responses. Our data suggest that pre-vaccination assessment offers insights into the innate mechanisms driving mRNA vaccine responses and has predictive potential.
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(This article belongs to the Section DNA and mRNA Vaccines)
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Open AccessReview
Challenges and Limitations of Current RSV Prevention Strategies in Infants and Young Children: A Narrative Review
by
Nicola Principi, Serafina Perrone and Susanna Esposito
Vaccines 2025, 13(7), 717; https://doi.org/10.3390/vaccines13070717 - 1 Jul 2025
Abstract
Background: Respiratory syncytial virus (RSV) remains a leading cause of lower respiratory tract infections and hospitalizations in infants and young children globally. Recently, RSV prevention has advanced with the introduction of nirsevimab, a long-acting monoclonal antibody, and the RSV preF vaccine for maternal
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Background: Respiratory syncytial virus (RSV) remains a leading cause of lower respiratory tract infections and hospitalizations in infants and young children globally. Recently, RSV prevention has advanced with the introduction of nirsevimab, a long-acting monoclonal antibody, and the RSV preF vaccine for maternal immunization. While these interventions have improved early protection, several limitations hinder their broader impact and long-term effectiveness. Methods: This narrative review synthesizes evidence from clinical trials, observational studies, and regulatory reports to evaluate the main limitations of nirsevimab and maternal RSV vaccination. Literature searches were conducted in major databases, focusing on efficacy, safety, immunogenicity, implementation, and population-specific challenges. Results: Both nirsevimab and maternal vaccination provide strong protection during the first six months of life, but their effectiveness wanes thereafter. This is concerning as nearly half of RSV-related deaths occur in children over six months old. Maternal vaccine efficacy is uncertain in very-preterm infants, and safety concerns persist, including potential associations with preterm birth, Guillain–Barré syndrome, and hypertensive disorders. Real-world data from low-income countries are lacking, limiting generalizability. Additionally, the risk of vaccine-associated enhanced disease (VAED), although unconfirmed, has delayed pediatric vaccine development. Emerging monoclonal antibodies and live-attenuated vaccines are under investigation to extend protection beyond infancy. Conclusions: Despite substantial progress, current RSV prevention strategies leave critical gaps, particularly for older infants and underserved populations. There is a pressing need for next-generation vaccines, enhanced pharmacovigilance, and equitable global implementation to ensure sustained and inclusive RSV protection.
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(This article belongs to the Special Issue Respiratory Syncytial Virus (RSV) Vaccine)
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How Immunization Information Systems Inform Age-Based HPV Vaccination Recommendations in the United States: A Mixed-Methods Study
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Nadja A. Vielot, Isabelle K. Bucklin, Kristy Westfall, Deanna Kepka, Gregory Zimet and Sherri Zorn
Vaccines 2025, 13(7), 716; https://doi.org/10.3390/vaccines13070716 - 30 Jun 2025
Abstract
Background: Immunization information systems (IISs) in the United States forecast vaccine due dates, which can inform when providers recommend vaccines to patients. IIS forecasting for HPV vaccination at 9 years, the minimum age of licensure, and when vaccination is likely most effective
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Background: Immunization information systems (IISs) in the United States forecast vaccine due dates, which can inform when providers recommend vaccines to patients. IIS forecasting for HPV vaccination at 9 years, the minimum age of licensure, and when vaccination is likely most effective is not documented or well-understood. Methods: We documented characteristics of HPV vaccination forecasts in jurisdictional IISs through Internet searches and requests to immunization program managers. Next, we conducted focus groups with stakeholders from seven jurisdictions to elucidate their processes for determining and implementing HPV vaccination forecasts. Results: Forecast data were available from 49 out of 64 CDC-funded jurisdictions, of which 14 (29%) recommended HPV vaccination at age 9 and 35 (71%) recommended HPV vaccination starting at ages 11 through to 15. Jurisdictions that recommended HPV vaccination at age 9 cited the positions of the American Cancer Society and American Academy of Pediatrics and reported little or no provider opposition to this recommendation. Jurisdictions reported variable flexibility in programming their forecasts. Those that changed their HPV vaccination forecast from 11 to 9 years did so easily while some experienced limitations. Other jurisdictions adhered strictly to the CDC’s routine recommendation at age 11–12 years and would only update the forecast in tandem with updated CDC guidance. The impact of IISs and electronic health record interoperability on how providers view and utilize IIS forecasting is unclear. Conclusions: Jurisdictions can share best practices for forecasting at 9 and future studies can evaluate the effects of forecasting age on the vaccination rates, providing evidence for nationwide vaccination recommendations.
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(This article belongs to the Special Issue Improving HPV Vaccination Coverage: Current Issues, Future Prospects and Strategies)
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Open AccessSystematic Review
Safety, Immunogenicity, and Efficacy of COVID-19 Vaccines in Radiation–Oncology Patients: A Systematic Review and Meta-Analysis
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Paul Thöne, Margot Egger, Michael Stephan Gruber, Georg Gruber, Christina Kasassov, Dalma Nyiri, Eva Weis, Helene Werl, Leonhard Trinkl, Wolfgang Lilleby, Martin Clodi, Elisabeth Bräutigam, Benjamin Dieplinger, Annette Aigner and Hans Geinitz
Vaccines 2025, 13(7), 715; https://doi.org/10.3390/vaccines13070715 - 30 Jun 2025
Abstract
Background/Objectives: The COVID-19 pandemic significantly threatened cancer patients and oncologic care. The rollout of vaccines emerged as a critical milestone, despite the initial lack of evidence regarding their safety and efficacy in this population. This systematic review and meta-analysis evaluate the current
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Background/Objectives: The COVID-19 pandemic significantly threatened cancer patients and oncologic care. The rollout of vaccines emerged as a critical milestone, despite the initial lack of evidence regarding their safety and efficacy in this population. This systematic review and meta-analysis evaluate the current evidence on COVID-19 vaccination in patients undergoing radiotherapy (RT). Methods: PubMed, Livivo, Scopus, and Cochrane Library were systematically reviewed for relevant publications on COVID-19 vaccination in the context of radiation oncology, published by 19 April 2024. The treatment effects were calculated as the proportion of seroconverted individuals. Results: A total of 22 studies published between 2021 and 2024 were included, covering various aspects of vaccination, including safety, tolerability, qualitative and quantitative humoral responses, cellular responses, vaccination efficacy, and booster vaccinations. Notably, patients undergoing RT exhibited a high willingness to receive vaccination. Vaccination was overall well tolerated and safe, with a low incidence of side effects, which were primarily mild. The primary meta-analysis showed a seroconversion proportion of 91% [95% CI: 84–96%] overall, with a somewhat higher proportion of 93% in patients receiving RT alone, compared to 90% in patients receiving either RT or RT combined with chemotherapy. Furthermore, immunization during RT led to a sustained increase in antibody titers, with a notable long-term persistence of IgG. Conclusions: COVID-19 vaccines demonstrate excellent safety, immunogenicity, and efficacy in patients receiving RT, who also exhibit a high willingness to be vaccinated. The outcomes observed are comparable to those in healthy controls and superior to those seen in patients receiving other cancer treatments, such as chemotherapy. The vaccination of radiation oncology patients in future pandemics or epidemics is strongly advocated even during active treatment.
Full article
(This article belongs to the Section COVID-19 Vaccines and Vaccination)
Open AccessArticle
Replication of Vectored Herpesvirus of Turkey (HVT) in a Continuous, Microcarrier-Independent Suspension Cell Line from Muscovy Duck
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Karoline Mähl, Deborah Horn, Sirine Abidi, Benedikt B. Kaufer, Volker Sandig, Alexander Karlas and Ingo Jordan
Vaccines 2025, 13(7), 714; https://doi.org/10.3390/vaccines13070714 - 30 Jun 2025
Abstract
Background/Objectives: More than 33 billion chickens are industrially raised for meat and egg production globally and vaccinated against Marek’s disease virus (MDV). The antigenically related herpesvirus of turkey (HVT) is used as a live-attenuated vaccine, commonly provided as a recombinant vector to protect
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Background/Objectives: More than 33 billion chickens are industrially raised for meat and egg production globally and vaccinated against Marek’s disease virus (MDV). The antigenically related herpesvirus of turkey (HVT) is used as a live-attenuated vaccine, commonly provided as a recombinant vector to protect chickens against additional unrelated pathogens. Because HVT replicates in a strictly cell-associated fashion to low levels of infectious units, adherent primary chicken or duck embryo fibroblasts are infected, dislodged from the cultivation surface and distributed as cryocultures in liquid nitrogen to the site of application. Although viable cells are complex products, application of infected cells in ovo confers protection even in presence of maternal antibodies. Methods/Results: The aim of our study was to determine whether a continuous cell line in a scalable cultivation format can be used for production of HVT-based vaccines. The AGE1.CR cell line (from Muscovy duck) was found to be highly permissive in adherent cultures. Propagation in suspension, however, initially gave very low yields. The induction of cell-to-cell contacts in carrier-independent suspensions and a metabolic shock improved titers to levels suitable for vaccine production (>105 infectious units/mL after infection with multiplicity of 0.001). Conclusions: Production of HVT is challenging to scale to large volumes and the reliance on embryonated eggs from biosecure facilities is complex. We demonstrate that a cell-associated HVT vector can be propagated in a carrier-independent suspension culture of AGE1.CR cells in chemically defined medium. The fed-batch production is independent of primary cells and animal-derived material and can be scaled to large volumes.
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(This article belongs to the Special Issue Animal Herpesviruses: 2nd Edition)
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Social Ecological Influences on HPV Vaccination Among Cape Verdean Immigrants in the U. S.: A Qualitative Study
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Ana Cristina Lindsay, Celestina V. Antunes, Aysha G. Pires, Monica Pereira and Denise L. Nogueira
Vaccines 2025, 13(7), 713; https://doi.org/10.3390/vaccines13070713 - 30 Jun 2025
Abstract
Background: Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States (U.S.) and a major contributor to several cancers, including cervical, anal, penile, and oropharyngeal cancers. Although a safe and effective vaccine is available, HPV vaccination rates remain suboptimal,
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Background: Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States (U.S.) and a major contributor to several cancers, including cervical, anal, penile, and oropharyngeal cancers. Although a safe and effective vaccine is available, HPV vaccination rates remain suboptimal, particularly among racial, ethnic, and immigrant minority groups. This study explored multiple factors, such as cultural, social, and structural influences, influencing HPV vaccine decision-making among Cape Verdean immigrant parents in the U.S., a population currently underrepresented in HPV research. Methods: Qualitative study using individual, in-depth interviews with Cape Verdean immigrant parents of children aged 11 to 17 years living in the U.S. Interviews were transcribed verbatim and analyzed thematically using the social ecological model (SEM) to identify barriers and facilitators at the intrapersonal, interpersonal, organizational, community, and policy levels. Results: Forty-five Cape Verdean parents (27 mothers, 18 fathers) participated. Fathers were significantly older than mothers (50.0 vs. 41.1 years, p = 0.05). Most were married or partnered (60%), had at least a high school education (84.4%), and reported annual household incomes of US$50,000 or more (66.7%), with no significant gender differences. Nearly all spoke Creole at home (95.6%). Fathers had lower acculturation than mothers (p = 0.05), reflecting less adaptation to U.S. norms and language use. Most parents had limited knowledge of HPV and the vaccine, with gendered beliefs and misconceptions about risk. Only seven mothers (25.9%) reported receiving a provider recommendation; all indicated that their children had initiated vaccination (1 dose or more). Mothers were the primary decision-makers, though joint decision-making was common. Trust in providers was high, but poor communication and the lack of culturally and linguistically appropriate materials limited informed decision-making. Stigma, misinformation, and cultural taboos restricted open dialogue. Trusted sources of information included schools, churches, and Cape Verdean organizations. While parents valued the U.S. healthcare system, they noted gaps in public health messaging and provider engagement. Conclusions: Findings revealed that HPV vaccine uptake and hesitancy among Cape Verdean immigrant parents in the U.S. were influenced by individual beliefs, family dynamics, healthcare provider interactions, cultural norms, and structural barriers. These findings highlight the need for multilevel strategies such as culturally tailored education, community engagement, and improved provider communication to support informed vaccination decisions in this population.
Full article
(This article belongs to the Special Issue Vaccine Strategies for HPV-Related Cancers: 2nd Edition)
Open AccessArticle
Adverse Events and Associated Economic Burden of COVID-19 Vaccination in Queensland, Australia: Findings from the Cross-Sectional QoVAX-Statewide Study
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Qing Xia, Kerry-Ann F. O’Grady, Peter Vardon, Selina Ward, Rebecca Gregory, Janet Davies and Hannah E. Carter
Vaccines 2025, 13(7), 712; https://doi.org/10.3390/vaccines13070712 - 30 Jun 2025
Abstract
Background/Objectives: The economic impact of adverse events following COVID-19 immunisation (AEFIs) in Australia is underexplored. This study aimed to assess the economic burden of AEFIs on both healthcare systems and societal productivity. Methods: A cross-sectional survey was conducted in Queensland residents
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Background/Objectives: The economic impact of adverse events following COVID-19 immunisation (AEFIs) in Australia is underexplored. This study aimed to assess the economic burden of AEFIs on both healthcare systems and societal productivity. Methods: A cross-sectional survey was conducted in Queensland residents aged ≥18 years who had received at least one dose of a COVID-19 vaccine in the preceding 12 months. Overall, 6964 participants were recruited from July to September 2022 via email and broad social media campaigns. The survey collected data on the incidence, type and duration of AEFIs; healthcare utilisation; and work-related absenteeism. Healthcare costs were estimated using national healthcare reimbursement data, and productivity costs were estimated using Australian Bureau of Statistics Average Weekly Earnings. Results: Of the 6797 eligible respondents (predominantly female [62%]; median age: 52 years), AEFIs were reported by 53.4%, 44.1%, 40.7%, and 40.9% following doses 1 to 4, respectively. Pain and tenderness were predominant local AEFIs, while tiredness and headaches were the most frequent systemic AEFIs, generally resolving within three days. Relatively few participants reporting AEFIs consulted medical professionals: 7.0%, 7.3%, 5.1%, and 1.9% following each dose, respectively. The mean healthcare cost per person reporting AEFIs was AUD 24, AUD 88, AUD 22, and AUD 4 following each respective dose. Work absenteeism was recorded in 16.5%, 18.2%, 15.2%, and 11.2% following each dose with mean absenteeism days per person of 4.7, 7.4, 3.6 and 2.1, respectively, and mean productivity costs per person reporting AEFIs amounting to AUD 1494, AUD 2388, AUD 1136, and AUD 690, respectively. Conclusions: Participants reported mostly mild AEFIs with only a small proportion of individuals seeking medical services. Productivity costs attributable to these AEFIs exceeded direct healthcare expenses incurred.
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(This article belongs to the Section COVID-19 Vaccines and Vaccination)
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Measles Epidemiology and Coverage of Immunization Against Measles in the Autonomous Province of Vojvodina, Serbia: Local Trends in a Regional Context
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Mioljub Ristić, Svetlana Ilić, Smiljana Rajčević, Mirjana Štrbac, Snežana Medić, Tatjana Pustahija, Vladimir Vuković, Marko Koprivica, Gorana Dragovac and Vladimir Petrović
Vaccines 2025, 13(7), 711; https://doi.org/10.3390/vaccines13070711 - 30 Jun 2025
Abstract
Background: Despite ongoing global elimination efforts, measles remains a persistent public health threat. Methods: This retrospective observational study examines trends in crude measles incidence and vaccination coverage from 1948 to 2024 in the northern region of Serbia—Autonomous Province of Vojvodina (AP Vojvodina)—which accounts
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Background: Despite ongoing global elimination efforts, measles remains a persistent public health threat. Methods: This retrospective observational study examines trends in crude measles incidence and vaccination coverage from 1948 to 2024 in the northern region of Serbia—Autonomous Province of Vojvodina (AP Vojvodina)—which accounts for 26.9% of the national population. This study further explores measles vaccination coverage across the province’s seven districts, along with the number of reported measles cases, age distribution, and vaccination status of affected individuals from 2000 to 2024. Data were obtained from official annual immunization records maintained by public health institutions within the framework of Serbia’s national mandatory immunization program. Results: A notable resurgence of measles occurred in Serbia during 2017–2018, following a decline in vaccination coverage. In AP Vojvodina, outbreaks were recorded in 2007, 2014–2015, and 2017–2018, predominantly affecting unvaccinated children and adults aged 20–39 years. Since 2019, the measles incidence has significantly declined. During the 2018 outbreak, the highest incidence was observed among children aged 1–4 years (40.6 per 100,000), followed by infants under 1 year (17.3 per 100,000) and adults aged 20–39 years (12.5 per 100,000). An analysis of the data from 2000 to 2024 revealed substantial age- and dose-related differences in measles incidence, particularly among unvaccinated individuals, those who had received one or two doses of a measles-containing vaccine (MCV), and those with unknown vaccination status. During the 2017–2018 epidemic, unvaccinated children under 1 year and those aged 1–4 years were the most affected. A marked increase in cases among single-dose recipients was noted in 2018, especially in adults aged 20–39 years (9.5%) and those ≥40 years (13.5%). A considerable proportion of measles cases in these age groups had unknown vaccination status: 33.1% among individuals aged 20–39 years and 18.2% among those aged ≥ 40 years. Epidemiological investigation linked the 2007 and 2014–2015 outbreaks in AP Vojvodina to importations from Bosnia and Herzegovina. No specific source was identified for the 2017–2018 outbreak, suggesting possible endemic transmission. Conclusions: These findings underscore the impact of fluctuating vaccination coverage on measles resurgence. Sustaining high two-dose MCV coverage, strengthening routine immunization programs, enhancing surveillance systems, and ensuring timely outbreak preparedness are critical measures for achieving effective measles control.
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(This article belongs to the Special Issue Epidemiology of Diseases Preventable by Vaccination)
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Open AccessArticle
In Situ Vaccination with a Vpr-Derived Peptide Elicits Systemic Antitumor Immunity by Improving Tumor Immunogenicity
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Danjie Pan, Ling Du, Jiayang Liu, Kudelaidi Kuerban, Xuan Huang, Yue Wang, Qiuyu Guo, Huaning Chen, Songna Wang, Li Wang, Pinghong Zhou, Zhefeng Meng and Li Ye
Vaccines 2025, 13(7), 710; https://doi.org/10.3390/vaccines13070710 - 30 Jun 2025
Abstract
Background: Cancer vaccines represent a groundbreaking advancement in cancer immunotherapy, utilizing tumor antigens to induce tumor-specific immune responses. However, challenges like tumor-induced immune resistance and technical barriers limit the widespread application of predefined antigen vaccines. Here, we investigated the potential of viral protein
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Background: Cancer vaccines represent a groundbreaking advancement in cancer immunotherapy, utilizing tumor antigens to induce tumor-specific immune responses. However, challenges like tumor-induced immune resistance and technical barriers limit the widespread application of predefined antigen vaccines. Here, we investigated the potential of viral protein R (Vpr) peptides as effective candidates for constructing anonymous antigen vaccines in situ by directly injecting at the tumor site and releasing whole-tumor antigens, inducing robust anti-tumor immune responses to overcome the limitations of predefined antigen vaccines. Methods: The cytotoxic effects of Vpr peptides were evaluated using the CCK8 reagent kit. Membrane penetration ability of Vpr peptides was observed using a confocal laser scanning microscope and quantitatively analyzed using flow cytometry. EGFR levels in the cell culture supernatants of cells treated with Vpr peptides were evaluated using an ELISA. Surface exposure of CRT on the tumor cell surface was observed using a confocal laser scanning microscope and quantitatively analyzed using flow cytometry. The secretion levels of ATP from tumor cells were evaluated using an ATP assay kit. HMGB1 release was evaluated using an ELISA. Mouse (Male C57BL/6 mice aged 4 weeks) MC38 and LLC bilateral subcutaneous tumor models were established to evaluate the therapeutic effects of Vpr peptides through in situ vaccination. Proteomic analysis was performed to explore the mechanism of anti-tumor activity of Vpr peptides. Results: Four Vpr peptides were designed and synthesized, with P1 and P4 exhibiting cytotoxic effects on tumor cells, inducing apoptosis and immunogenic cell death. In mouse tumor models, in situ vaccination with Vpr peptide significantly inhibited tumor growth and activated various immune cells. High-dose P1 monotherapy demonstrated potent anti-tumor effects, activating DCs, T cells, and macrophages. Combining ISV of P1 with a CD47 inhibitor SIRPαFc fusion protein showed potent distant tumor suppression effects. Proteomic analysis suggested that Vpr peptides exerted anti-tumor effects by disrupting tumor cell morphology, movement, and adhesion, and promoting immune cell infiltration. Conclusions: The designed Vpr peptides show promise as candidates for in situ vaccination, with significant anti-tumor effects, immune activation, and favorable safety profiles observed in mouse models. In situ vaccination with Vpr-derived peptides represents a potential approach for cancer immunotherapy.
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(This article belongs to the Special Issue New Approaches to Vaccine Development and Delivery)
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Open AccessArticle
Field Monitoring of Colostral BVDV-, BoHV-1-, and BRSV-Specific Serum Antibody Levels in Dairy Calves from Birth to Weaning Fed with Pasteurized Colostrum Pools Obtained from Vaccinated Dams
by
Veysel Soydal Ataseven, Ufuk Kaya, Müge Doğan, Sultan Şengül, Seda Turan, Fatma Türkarslan Akbaba and İsmail İlker Kocaer
Vaccines 2025, 13(7), 709; https://doi.org/10.3390/vaccines13070709 - 29 Jun 2025
Abstract
Background/Objectives: This study aimed to determine the changes in BVDV (bovine viral diarrhea virus), BoHV-1 (bovine herpesvirus-1), and BRSV (bovine respiratory syncytial virus) antibody levels until weaning in calves who ingested colostrum from vaccinated dairy cattle. Additionally, it aimed to measure the
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Background/Objectives: This study aimed to determine the changes in BVDV (bovine viral diarrhea virus), BoHV-1 (bovine herpesvirus-1), and BRSV (bovine respiratory syncytial virus) antibody levels until weaning in calves who ingested colostrum from vaccinated dairy cattle. Additionally, it aimed to measure the antibody levels induced by the vaccine administered before and after socialization after weaning. Methods: Exposure to respiratory viral and bacterial agents was monitored by PCR analysis using nasal swabs at regular intervals from birth to weaning (pre-colostral and after the 2nd, 7th, 15th, 25th, 35th, 45th, 55th, and 65th days). The levels of colostral BVDV, BoHV-1, and BRSV antibodies were monitored using an enzyme-linked immunosorbent assay (ELISA) at the same intervals from birth to weaning (pre-colostral and after the 2nd, 7th, 15th, 25th, 35th, 45th, 55th, and 65th days). Results: The highest level of maternal antibodies in the blood was detected on day 7. BoHV-1, BVDV, and BRSV antibody levels decreased steadily until weaning by 69.14%, 38%, and 53%, respectively. Conclusions: Vaccination strategies should be planned by considering the presence of maternally derived antibodies and minimizing stress that may negatively affect vaccine titers, thus maximizing vaccine efficacy in calves.
Full article
(This article belongs to the Special Issue Vaccine and Vaccination in Veterinary Medicine)
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Open AccessArticle
Comparative Study of Two Immunisation Protocols in Goats Using Thiol-Sepharose Chromatography-Enriched Extracts from Adult Haemonchus contortus Worms
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Magnolia M. Conde-Felipe, José Adrián Molina, Antonio Ruiz, Otilia Ferrer, Mª Cristina Del Rio, Emma Carmelo, Juan R. Hernández-Fernaud, Francisco Rodríguez and José Manuel Molina
Vaccines 2025, 13(7), 708; https://doi.org/10.3390/vaccines13070708 - 29 Jun 2025
Abstract
Background: A comparative analysis was conducted between two immunisation protocols using different amounts of protein extracts from adult Haemonchus contortus worms, purified by thiol-Sepharose chromatography (625 μg/animal vs. 200 μg/animal). These protocols involved either five or two inoculations of the immunogen, respectively.
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Background: A comparative analysis was conducted between two immunisation protocols using different amounts of protein extracts from adult Haemonchus contortus worms, purified by thiol-Sepharose chromatography (625 μg/animal vs. 200 μg/animal). These protocols involved either five or two inoculations of the immunogen, respectively. Methods: To evaluate the level of immunoprotection, animals were challenged with L3 of H. contortus two weeks after the last inoculation of the immunogen and humanely sacrificed at 8 weeks post-infection. Parasitological, biopathological, and serological parameters were monitored through the experiment. Parasite burden, abomasal-specific antibody responses, and histopathological changes were determined at the end of the trial. Results: The immunisation protocols resulted in similar reductions in cumulative faecal egg counts (60.5–64.9%) and the total worm burden (47.5–50%) compared to non-immunized (control) animals. Overall, these parasitological data showed an early recovery of the haematocrit (PCV) after challenge in the immunised groups relative to control. Similarly, levels of H. contortus-specific IgG and IgA antibodies increased in both the serum and gastric mucus of immunised groups. Conclusions: These findings represent a further step towards the potential application of this type of immunogen under field conditions, as protective responses (associated with a reduction in faecal egg output) were achieved using a simplified protocol, with lower immunogen doses and fewer inoculations required to induce immunoprotection, thereby mitigating the pathological effects of the parasite and reducing its ability to spread and infect susceptible hosts.
Full article
(This article belongs to the Special Issue Infectious Diseases and Immunization in Animals)
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Open AccessArticle
Nasopharyngeal Carriage, Serotype Distribution, and Antimicrobial Susceptibility of Streptococcus pneumoniae Among PCV13-Vaccinated and -Unvaccinated Children in Iran
by
Fatemeh Ashrafian, Mona Sadat Larijani, Saiedeh Haji Maghsoudi, Delaram Doroud, Alireza Fahimzad, Zahra Pournasiri, Elham Jafari, Masoumeh Parzadeh, Sara Abdollahi, Elham Haj Agha Gholizadeh Khiavi, Anahita Bavand, Morvarid Shafiei, Mahdi Rohani and Amitis Ramezani
Vaccines 2025, 13(7), 707; https://doi.org/10.3390/vaccines13070707 - 29 Jun 2025
Abstract
Background and Aim: Pneumococcal pneumonia is a major cause of death globally, emphasizing the importance of vaccination, especially in low- and middle-income countries. In Iran, the 13-valent pneumococcal conjugate vaccine (PCV13) is available exclusively through private healthcare systems, resulting in a lack
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Background and Aim: Pneumococcal pneumonia is a major cause of death globally, emphasizing the importance of vaccination, especially in low- and middle-income countries. In Iran, the 13-valent pneumococcal conjugate vaccine (PCV13) is available exclusively through private healthcare systems, resulting in a lack of studies on the prevalence of Streptococcus pneumoniae (S. pneumoniae) serotypes among vaccinated children. This research aimed to explore and compare the prevalence of nasopharyngeal pneumococcal carriage, serotype distribution, and antibiotic resistance patterns in healthy PCV13-vaccinated and -unvaccinated children. Methods: From August 2023 to November 2024, a multi-center, cross-sectional observational study was conducted in Tehran, Iran. This study included 204 nasopharyngeal samples collected from children aged from 18 to 59 months, involving both cases of children vaccinated with PCV13 and unvaccinated populations. S. pneumoniae was identified through a combination of culture methods and biochemical tests, confirmed by real-time PCR. Serotyping was achieved using cpsB sequencing, and the minimum inhibitory concentration method was employed to assess antibiotic resistance. Results: This study revealed similar S. pneumoniae carriage rates between PCV13-vaccinated and -unvaccinated Iranian children (20.6% vs. 21.6%). Serotypes 23F and 19F were prevalent in unvaccinated children, while 15B/15C was more prevalent in PCV13-vaccinated children. The included S. pneumoniae serotypes in PCV13 were detected more in the unvaccinated group. PCV13-vaccinated children exhibited no penicillin-resistant pneumococcal isolates, although four isolates were non-susceptible in unvaccinated children. Both groups showed substantial resistance to erythromycin and SXT. Previous respiratory infections, daycare attendance, residence in Tehran, and a history of antibiotic consumption increased the risk of pneumococcal carriage. Conclusions: PCV13 vaccination influences pneumococcal serotype distribution and antimicrobial susceptibility, although there was no significant difference regarding carriage rates between vaccinated and unvaccinated groups. These findings highlight the critical importance of vaccination in reducing invasive serotypes and antimicrobial resistance in children under five years old, emphasizing the importance of national PCV vaccination programs alongside continuous serotype surveillance.
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(This article belongs to the Section Epidemiology)
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BCG Vaccination Potentially Modulates the Transcriptome of Infant CD4 T Cells in Addition to Age-Dependent Immune Ontogeny-Associated Changes
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Vidya Vijayan Karuvan Kandiyil, Eunchong Kang, Emily Coates, Portia Kamthunzi, Gerald Tegha, Mina Hosseinipour, Di Wu, Fei Zou and Kristina De Paris
Vaccines 2025, 13(7), 706; https://doi.org/10.3390/vaccines13070706 - 29 Jun 2025
Abstract
Background: The Bacille Calmette–Guérin (BCG) vaccine is part of the Extended Programme on Immunization (EPI) and as such is generally administered at birth. The global introduction of BCG not only protected many vaccinated infants against severe complications of tuberculosis but also resulted in
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Background: The Bacille Calmette–Guérin (BCG) vaccine is part of the Extended Programme on Immunization (EPI) and as such is generally administered at birth. The global introduction of BCG not only protected many vaccinated infants against severe complications of tuberculosis but also resulted in markedly reduced overall childhood mortality. Studies in human adults determined that BCG vaccination induces epigenetic reprogramming of innate immune cells (also known as trained immunity) and can also enhance T cell responses to both mycobacterial and non-mycobacterial antigens. Goal and Methods: The current study tested the hypothesis that BCG immunization similarly impacts the functionally distinct infant immune system. Towards this goal, we applied RNA sequencing to assess transcriptome changes in circulating CD4+ T cells of Malawian infants prior to and 2 to 13 weeks after BCG immunization. Results: In the first three months of life, transcriptome changes of infant CD4 T cells implied a functional shift towards T helper 1 and Th17 immunity. Vaccination with BCG resulted in additional modulation of the CD4 T cell transcriptome and differentially expressed genes could be linked to metabolomic function. Conclusions: These findings are consistent with data reported in BCG vaccinated adults and contribute to the understanding of molecular changes in infant CD4 T cells that may explain the improved capacity of the infant immune system to respond to pathogens after BCG vaccination.
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(This article belongs to the Section Attenuated/Inactivated/Live and Vectored Vaccines)
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Open AccessArticle
Influenza Vaccination Coverage Among Elderly Patients with Chronic Lung Respiratory Disease in Ningbo, China: Impact of Free Vaccination Policies and the COVID-19 Pandemic
by
Xiaoqing Wu, Jieping Chen, Pingping Li, Tianchi Yang and Lixia Ye
Vaccines 2025, 13(7), 705; https://doi.org/10.3390/vaccines13070705 - 29 Jun 2025
Abstract
Background: Elderly patients with chronic lower respiratory diseases (CLRDs) demonstrate an increased susceptibility to complications arising from influenza. Influenza vaccination remains the most effective strategy against influenza-related diseases among elderly CLRD patients. This study aimed to evaluate the influenza vaccination status of older
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Background: Elderly patients with chronic lower respiratory diseases (CLRDs) demonstrate an increased susceptibility to complications arising from influenza. Influenza vaccination remains the most effective strategy against influenza-related diseases among elderly CLRD patients. This study aimed to evaluate the influenza vaccination status of older CLRD patients and the factors affecting influenza vaccination. Methods: Using population-based health registries, we analyzed the longitudinal uptake of influenza vaccination among elderly patients with CLRDs in Ningbo from the 2018/19 season to the 2022/23 season. A multivariate logistic regression analysis was performed to identify behavioral determinants influencing influenza vaccination among elderly CLRD patients under Ningbo’s post-pandemic free vaccination policy. Results: An average of 487,309 older patients with CLRDs were included in our analysis for each season. The influenza vaccination rate increased from 3.59% in 2018/19 to 43.32% in the 2022/23 influenza season. There was a significant increase in the proportion of timely influenza vaccinations prior to November 15, rising from 3.01% before the COVID-19 pandemic to 33.90% during the pandemic period. The multivariate logistic regression analysis indicated that both the COVID-19 pandemic and free vaccination policy significantly promoted influenza vaccine uptake. Older CLRD patients with comorbidities such as diabetes, hypertension, or cancer exhibited higher influenza vaccination coverage, whereas those who have experienced acute cardiovascular events showed a lower vaccination rate. Additionally, a prior vaccination history significantly influenced uptake. Conclusions: Despite the significant improvement in vaccination rates, coverage among elderly patients with CLRDs remains below the WHO target. Addressing this gap requires integrated interventions that combine expanding the population eligible for free vaccinations, community mobilization efforts, and effective communication regarding cardiovascular safety to mitigate vaccine hesitancy within high-risk groups.
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(This article belongs to the Section Human Vaccines and Public Health)
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Open AccessArticle
Evaluation of Recombinant Foot-and-Mouth Disease SAT2 Vaccine Strain in Terms of Antigen Productivity, Virus Inactivation Kinetics, and Immunogenicity in Pigs for Domestic Antigen Bank
by
Jae Young Kim, Sun Young Park, Gyeongmin Lee, Mijung Kwon, Jong Sook Jin, Jong-Hyeon Park and Young-Joon Ko
Vaccines 2025, 13(7), 704; https://doi.org/10.3390/vaccines13070704 - 28 Jun 2025
Abstract
Background: Since the massive outbreak of foot-and-mouth disease (FMD) in South Korea in 2010–2011, cloven-hoofed livestock have been immunized with serotype O and A vaccines across the country. Other serotypes of FMD vaccines were stockpiled in overseas FMD vaccine factories as antigen banks.
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Background: Since the massive outbreak of foot-and-mouth disease (FMD) in South Korea in 2010–2011, cloven-hoofed livestock have been immunized with serotype O and A vaccines across the country. Other serotypes of FMD vaccines were stockpiled in overseas FMD vaccine factories as antigen banks. Once a manufacturing facility has been established in South Korea, the overseas antigen banks will be replaced by domestic one. Therefore, this study aimed to evaluate the commercial potential of the previously developed SAT2 vaccine candidate (SAT2 ZIM-R). Methods: The optimal condition was determined at various virus concentrations, infection times, and pH levels, resulting in 0.01 MOI for SAT2 ZIM-R for 24 h infection at a pH of 7.5. Results: When the SAT2 ZIM-R virus was produced in flasks from 40 to 1000 mL in fivefold increments, all scales of production yielded > 7.0 µg/mL of antigens. Using a bioreactor, 5.6 µg/mL of antigens was recovered from a 1 L viral culture. The optimal conditions of viral inactivation kinetics were determined to be 1 mM of binary ethyleneimine (BEI) treatment at 26 °C for 24 h, with approximately 91% of the antigen being retained after virus inactivation. When the SAT2 ZIM-R experimental vaccine was administered twice to pigs, the neutralizing antibody titer increased approximately 500-fold after booster immunization. Conclusions: To the best of our knowledge, this is the first study to evaluate the antigen productivity, viral inactivation kinetics, and immunogenicity of the SAT vaccine strain in pigs. In the future, the SAT2 ZIM-R vaccine may be a useful candidate vaccine for a domestic antigen bank.
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(This article belongs to the Special Issue Innovations in Vaccine Technology)
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Recent Advances in Bioconjugate Vaccine Development
by
Brendan W. Wren, Catherine L. Hall, Vanessa S. Terra, Mark A. Harrison, Elizabeth Atkins, Fauzy Nasher and Ian J. Passmore
Vaccines 2025, 13(7), 703; https://doi.org/10.3390/vaccines13070703 - 28 Jun 2025
Abstract
Glycoconjugate vaccines, consisting of a protein component covalently linked to a glycan antigen, have led to a significant reduction in the global occurrence of bacterial meningitis and pneumonia. They provide robust, lasting immunity in all age groups. However, their production by traditional chemical
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Glycoconjugate vaccines, consisting of a protein component covalently linked to a glycan antigen, have led to a significant reduction in the global occurrence of bacterial meningitis and pneumonia. They provide robust, lasting immunity in all age groups. However, their production by traditional chemical conjugation approaches has drawbacks in terms of complexity, cost, and lack of flexibility in design, which explains their limited application to a few pathogenic bacteria in the past four decades. Protein glycan coupling technology (PGCT) or bioconjugation, where glycoconjugates are produced in purpose-engineered bacterial cells, is a useful alternative to chemical conjugation and promises an array of low-cost custom-made glycoconjugate vaccines with vast protein glycan combinations. The technology has undergone significant development since its inception, and new advances and refinements continually drive the field forward. Several bioconjugate vaccines are currently in clinical trials, demonstrating the potential of the technology. We will review the wide applicability of bioconjugation and recent developments in each of the components of the technology, namely, glycan expression, protein selection, and the coupling of selected glycan with proteins, all within custom-designed E. coli cells. These advances promise to deliver effective glycoconjugate vaccines for multiple unmet medical needs.
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(This article belongs to the Special Issue The Current Development of Glycoconjugate Vaccines for Infectious Diseases)
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An mRNA Vaccine Expressing Blood-Stage Malaria Antigens Induces Complete Protection Against Lethal Plasmodium yoelii
by
Amy C. Ott, Patrick J. Loll and James M. Burns, Jr.
Vaccines 2025, 13(7), 702; https://doi.org/10.3390/vaccines13070702 - 28 Jun 2025
Abstract
Background and Objectives: To evaluate the mRNA vaccine platform for blood-stage Plasmodium parasites, we completed a proof-of-concept study using the P. yoelii mouse model of malaria and two mRNA-based vaccines. Both encoded PyMSP119 fused to PyMSP8 (PyMSP1/8). One
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Background and Objectives: To evaluate the mRNA vaccine platform for blood-stage Plasmodium parasites, we completed a proof-of-concept study using the P. yoelii mouse model of malaria and two mRNA-based vaccines. Both encoded PyMSP119 fused to PyMSP8 (PyMSP1/8). One was designed for secretion of the encoded protein (PyMSP1/8-sec); the other encoded membrane-bound antigen (PyMSP1/8-mem). Methods: Secretion of PyMSP1/8-sec and membrane localization of PyMSP1/8-mem were verified in mRNA-transfected cells. As recombinant PyMSP1/8 (rPyMSP1/8) is known to protect mice against lethal P. yoelii 17XL infection, we first compared immunogenicity and efficacy of the PyMSP1/8-sec mRNA vaccine versus the recombinant formulation in outbred mice. Animals were immunized three times followed by challenge with a lethal dose of P. yoelii 17XL-parasitized RBCs (pRBCs). Similar immunization and challenge experiments were conducted to compare PyMSP1/8-sec versus PyMSP1/8-mem mRNA vaccines. Results: Immunogenicity of the PyMSP1/8-sec mRNA vaccine was superior to the recombinant formulation, inducing higher antibody titers against both vaccine components. Following challenge with P. yoelii 17XL pRBCs, all PyMSP1/8-sec-immunized animals survived, with 50% of these showing no detectible pRBCs in circulation (<0.01%). In addition, mean peak parasitemia in PyMSP1/8-sec mRNA-immunized mice was significantly lower than that in the rPyMSP1/8 vaccine group. Both PyMSP1/8-sec and PyMSP1/8-mem were protective against P. yoelii 17XL challenge, with PyMSP1/8-mem immunization providing a significantly higher level of protection than PyMSP1/8-sec immunization considering the number of animals with no detectable pRBCs in circulation and the mean peak parasitemia in animals with detectable parasitemia. Conclusions: mRNA vaccines were highly immunogenic and potently protective against blood-stage malaria, outperforming a similar recombinant-based vaccine. The membrane-bound antigen was more effective at inducing protective antibody responses, highlighting the need to consider antigen localization for mRNA vaccine design.
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(This article belongs to the Special Issue Vaccination Against Vector-Borne Diseases: Bridging Public Health and Epidemiology)
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Immunogenicity of Matrix Protein 2 Ectodomain (M2e) Displayed on Nodavirus-like Particles as Avian Influenza Vaccine for Poultry
by
Anis Suraya Mohamad Abir, Wen Siang Tan, Abdul Rahman Omar, Kok Lian Ho, Munir Iqbal and Abdul Razak Mariatulqabtiah
Vaccines 2025, 13(7), 701; https://doi.org/10.3390/vaccines13070701 - 27 Jun 2025
Abstract
Avian influenza is an economically significant disease affecting poultry worldwide and is caused by influenza A viruses that can range from low to highly pathogenic strains. These viruses primarily target the respiratory, digestive, and nervous systems of birds, leading to severe outbreaks that
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Avian influenza is an economically significant disease affecting poultry worldwide and is caused by influenza A viruses that can range from low to highly pathogenic strains. These viruses primarily target the respiratory, digestive, and nervous systems of birds, leading to severe outbreaks that threaten poultry production and pose zoonotic risks. The ectodomain of the avian influenza virus (AIV) matrix protein 2 (M2e), known for its high conservation across influenza strains, has emerged as a promising candidate for developing a universal influenza vaccine in a mouse model. However, the efficacy of such expression against poultry AIVs remains limited. The objective of this study was to evaluate the immunogenicity of nodavirus-like particles displaying the M2e proteins. In this study, three synthetic heterologous M2e genes originated from AIV strains H5N1, H9N2 and H5N2 were fused with the nodavirus capsid protein (NVC) of the giant freshwater prawn Macrobrachium rosenbergii (NVC-3xAvM2e) prior to immunogenicity characterisations in chickens. The expression vector pTRcHis-TARNA2 carrying the NVC-3xAvM2e gene cassette was introduced into E. coli TOP-10 cells. The recombinant proteins were purified, inoculated into one-week-old specific pathogen-free chickens subcutaneously and analysed. The recombinant protein NVC-3xAvM2e formed virus-like particles (VLPs) of approximately 25 nm in diameter when observed under a transmission electron microscope. Dynamic light scattering (DLS) analysis revealed that the VLPs have a polydispersity index (PDI) of 0.198. A direct ELISA upon animal experiments showed that M2e-specific antibodies were significantly increased in vaccinated chickens after the booster, with H5N1 M2e peptides having the highest mean absorbance value when compared with those of H9N2 and H5N2. A challenge study using low pathogenic AIV (LPAI) strain A/chicken/Malaysia/UPM994/2018 (H9N2) at 106.5 EID50 showed significant viral load in the lung and cloaca, but not in the oropharyngeal of vaccinated animals when compared with the unvaccinated control group. Collectively, this study suggests that nodavirus-like particles displaying three heterologous M2e have the potential to provide protection against LPAI H9N2 in chickens, though the vaccine’s efficacy and cross-protection across different haemagglutinin (HA) subtypes should be further evaluated.
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(This article belongs to the Special Issue Veterinary Vaccines and Host Immune Responses)
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