Vaccines

7 pages, 156 KiB

Open AccessConference Report

Strengthening Vaccine Safety Systems, Research, and Regional Collaboration in Africa: A Call to Action

by Beckie N. Tagbo, Chioma S. Ejekam, Winfred Oppong-Amoako, Tene Marceline Yameogo, Afework Mitiku, Dorothy O. Esangbedo, Nelisiwe Khuzwayo, Gugu Mahlangu, Samia M. Badar, Edinam A. Agbenu, Rhanda M. Adechina and Kwasi A. Nyarko

Vaccines 2025, 13(6), 661; https://doi.org/10.3390/vaccines13060661 - 19 Jun 2025

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Abstract

The 8th meeting of the African Advisory Committee on Vaccine Safety (AACVS), constituted in 2021, convened by the Vaccine Research and Innovation Unit within the Vaccine Preventable Diseases Program, WHO Regional Office for Africa, was held virtually from 14 to 16 April 2025. [...] Read more.

The 8th meeting of the African Advisory Committee on Vaccine Safety (AACVS), constituted in 2021, convened by the Vaccine Research and Innovation Unit within the Vaccine Preventable Diseases Program, WHO Regional Office for Africa, was held virtually from 14 to 16 April 2025. The meeting brought together independent vaccine experts to provide advice to the Regional Director, WHO, on vaccine safety issues critical to the African region. Discussions focused on critical updates regarding ongoing regional outbreaks, safety data, and associated safety concerns, with emphasis on newly introduced vaccines, including the malaria vaccines (RTS, S and R21), the MenFive pentavalent meningitis vaccine, and the Mpox vaccines—MVA-BN and LC16—alongside the ongoing Mpox response. The Committee conducted a deep dive into comprehensive safety considerations for new vaccine introduction, active surveillance strategies, strengthening the responsiveness of pharmacovigilance systems, and advancing vaccine research and development in Africa. Key observations highlighted significant gaps in safety surveillance systems. These included delays in data collection, access, and signal detection; a lack of harmonized real-time monitoring frameworks; the underutilization of digital technologies; and inadequate manufacturer responsibilities and accountability in post-market safety monitoring. The meeting concluded with a call to action emphasizing the need for sustainable pharmacovigilance funding mechanisms, improved regional coordination, real-time data sharing, standardized early safety study protocols, strengthened manufacturer accountability, and investments in risk communication and community engagement to bolster public trust. Strengthening vaccine safety systems and enhancing regional collaboration were recognized as urgent priorities to support the safe and effective deployment of vaccines and protect public health across Africa. Full article

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

15 pages, 228 KiB

Open AccessArticle

Body Mass Index and COVID-19: An Overview Among an Italian Multicentric Cohort of Healthcare Workers in the Pre- and Post-Vaccination Eras—ORCHESTRA Project

by Gianluca Spiteri, Lorena Torroni, Maria Grazia Lourdes Monaco, Angela Carta, Francesco Taus, Alberto Modenese, Loretta Casolari, Maria Luisa Scapellato, Filippo Liviero, Francesca Larese Filon, Francesca Rui, Giuseppe Verlato and Stefano Porru

Vaccines 2025, 13(6), 660; https://doi.org/10.3390/vaccines13060660 - 19 Jun 2025

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Abstract

Background The prevalence of obesity is increasing all over the world, resulting in a global health emergency. The impact of obesity on the risk of SARS-CoV-2 infection and symptom severity, especially among high-risk working populations such as health workers, deserves further studies. Methods [...] Read more.

Background The prevalence of obesity is increasing all over the world, resulting in a global health emergency. The impact of obesity on the risk of SARS-CoV-2 infection and symptom severity, especially among high-risk working populations such as health workers, deserves further studies. Methods A multicentric retrospective cohort study was conducted among health workers at four Italian University Hospitals belonging to the ORCHESTRA Project. Data were collected through an online survey, investigating sociodemographic and clinical data, until September 2022. Results The questionnaire was filled out by 5777 health workers. The median age was 46 years old (I–III quartile 20–72) and 75.5% were females. Data on BMI was available for 5470 participants. Overweight and obese subjects amounted to 23.4% and 9.8%, respectively. Naïve health workers were the majority (57.4%). Overweight and obese subjects were at a higher risk of infection only before vaccination with respect to normoweight subjects (RRR = 1.28 (IC 95% 1.01–1.62, p = 0.039) and 1.36 (1.00–1.86, p = 0.047), respectively). Major acute and post-acute COVID-19 symptoms were more common among obese subjects, as compared to those with a normal weight (35.2% vs. 23.5%, and 14.2% vs. 9.3%). BMI did not reduce antibody levels after vaccination. On the contrary, overweight and obese health workers had a significantly higher RGM after the third dose (1.12 and 1.48, respectively; normal weight as reference). Conclusions Overweight and obese subjects are at a higher risk of SARS-CoV-2 infection. However, SARS-CoV-2 vaccination fosters a high antibody response even in these individuals. Vaccination against SARS-CoV-2 should be prioritized in subjects with a high BMI, especially in highly exposed workers, such as health workers. Full article

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

15 pages, 1952 KiB

Open AccessArticle

Engineering and Evaluation of a Live-Attenuated Vaccine Candidate with Enhanced Type 1 Fimbriae Expression to Optimize Protection Against Salmonella Typhimurium

by Patricia García, Arianna Rodríguez-Coello, Andrea García-Pose, María Del Carmen Fernández-López, Andrea Muras, Miriam Moscoso, Alejandro Beceiro and Germán Bou

Vaccines 2025, 13(6), 659; https://doi.org/10.3390/vaccines13060659 - 19 Jun 2025

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Abstract

Background:Salmonella Typhimurium is a major zoonotic pathogen, in which type 1 fimbriae play a crucial role in intestinal colonization and immune modulation. This study aimed to improve the protective immunity of a previously developed growth-deficient strain—a double auxotroph for D-glutamate and D-alanine—by [...] Read more.

Background:Salmonella Typhimurium is a major zoonotic pathogen, in which type 1 fimbriae play a crucial role in intestinal colonization and immune modulation. This study aimed to improve the protective immunity of a previously developed growth-deficient strain—a double auxotroph for D-glutamate and D-alanine—by engineering the inducible expression of type 1 fimbriae. Methods: P_tetA-driven expression of the fim operon was achieved by λ-Red mutagenesis. fimA expression was quantified by qRT-PCR, and fimbriation visualized by transmission electron microscopy. Adhesive properties were evaluated through FimH sequence analysis, yeast agglutination, mannose-binding/inhibition assays, and HT-29 cell adherence. BALB/c mice were immunized orogastrically with IRTA ΔΔΔ or IRTA ΔΔΔ P_tetA::fim. Safety and immunogenicity were assessed by clinical monitoring, bacterial load, fecal shedding, ELISA tests, and adhesion/blocking assays using fecal extracts. Protection was evaluated after challenging with wild-type and heterologous strains. Results: IRTA ΔΔΔ P_tetA::fim showed robust fimA expression, dense fimbrial coverage, a marked mannose-sensitive adhesive phenotype and enhanced HT-29 attachment. Fimbrial overexpression did not alter intestinal colonization or translocation to mesenteric lymph nodes (mLNs). Immunization elicited a mixed IgG1/IgG2a, significantly increased IgA and IgG against type 1 fimbriae-expressing Salmonella, and enhanced the ability of fecal extracts to inhibit the adherence of wild-type strains. Upon challenge (IRTA wild-type/20220258), IRTA ΔΔΔ P_tetA::fim reduced infection burden in the cecum (−1.46/1.47-log), large intestine (−1.35/2.17-log), mLNs (−1.32/0.98-log) and systemic organs more effectively than IRTA ΔΔΔ. Conclusions: Inducible expression of type 1 fimbriae enhances mucosal immunity and protection, supporting their inclusion in next-generation Salmonella vaccines. Future work should assess cross-protection and optimize FimH-mediated targeting for mucosal delivery. Full article

(This article belongs to the Special Issue Vaccine Design and Development)

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21 pages, 1081 KiB

Open AccessArticle

HPV Knowledge, Vaccination Uptake, and Salivary Diagnostics Among Dental Students in Romania

by Sergiu Baranga, Doina Chioran, Octavia Balean, Ramona Dumitrescu, Roxana Popescu, Daniela Jumanca, Roxana Oancea, Ruxandra Sava-Rosianu, Vanessa Bolchis and Atena Galuscan

Vaccines 2025, 13(6), 658; https://doi.org/10.3390/vaccines13060658 - 19 Jun 2025

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Abstract

Background: Human papillomavirus (HPV) is a key cause of cervical and oropharyngeal cancers. Despite available vaccines, uptake remains low in Romania due to limited awareness and hesitancy. This study assessed HPV knowledge, vaccination status, and the presence of high-risk strains (16 and 18) [...] Read more.

Background: Human papillomavirus (HPV) is a key cause of cervical and oropharyngeal cancers. Despite available vaccines, uptake remains low in Romania due to limited awareness and hesitancy. This study assessed HPV knowledge, vaccination status, and the presence of high-risk strains (16 and 18) in the saliva of dental students from Victor Babeș University in Timișoara. Methods: A cross-sectional study was conducted between February and March 2024, enrolling 199 dental students. Participants completed a 15-item questionnaire addressing HPV-related knowledge, vaccination status, lifestyle factors, and health history. Saliva samples were collected and analyzed using real-time PCR for the detection of HPV types 16 and 18. Logistic regression analysis was employed to identify predictors of vaccination uptake. Results: Only 10.6% of participants had received the HPV vaccine, although 96.9% acknowledged its safety and efficacy. Awareness was higher among females (88.1%) than males (84.3%), and vaccination rates were significantly greater among students under 25 years old (p = 0.0312). A total of 16.6% reported the presence of papillomas or warts. HPV DNA was detected in 10% of saliva samples. Conclusions: Although awareness of HPV was high, vaccination rates remained low, revealing a gap between knowledge and preventive action. Saliva-based screening shows promise as a non-invasive diagnostic tool, and integrating targeted education and advocacy into dental curricula may enhance public health outcomes in Romania. Full article

(This article belongs to the Special Issue Improving HPV Vaccination Coverage: Current Issues, Future Prospects and Strategies)

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21 pages, 1238 KiB

Open AccessArticle

An In-House ELISA for Anti-Porcine Circovirus Type 2d (PCV2d) IgG: Analytical Validation and Serological Correlation

by Gyeong-Seo Park, Byoung Joo Seo, Woo Ju Kwon, Yeong Lee Seok, Hyo Jeong Lee, Sung Ho Lee, Minju Kim, MinChul Lee, Chanhee Chae and Chonghan Kim

Vaccines 2025, 13(6), 657; https://doi.org/10.3390/vaccines13060657 - 19 Jun 2025

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Abstract

Background/Objectives: Porcine circovirus type 2d (PCV2d) is the predominant genotype associated with porcine circovirus-associated disease (PCVAD), leading to significant economic losses. In South Korea, current vaccine lot-release testing relies on a T/C-ratio-based guinea pig assay, which lacks scientific justification and methodological robustness. [...] Read more.

Background/Objectives: Porcine circovirus type 2d (PCV2d) is the predominant genotype associated with porcine circovirus-associated disease (PCVAD), leading to significant economic losses. In South Korea, current vaccine lot-release testing relies on a T/C-ratio-based guinea pig assay, which lacks scientific justification and methodological robustness. This study aimed to develop and validate a statistically defined in-house ELISA using rabbit-derived polyclonal antibodies against PCV2d for the standardized evaluation of immunogenicity. Methods: Polyclonal IgG was generated by immunizing a rabbit with inactivated PCV2d, and it was purified through Protein A chromatography. Guinea pigs (n = 18) were immunized with IMMUNIS^® DMVac, an inactivated PCV2d vaccine candidate developed by WOOGENE B&G, at different doses. In-house ELISA parameters were optimized (antigen coating, blocking agent, and substrate incubation), and analytical performance was evaluated by ROC, linearity, reproducibility, and specificity. Sera from guinea pigs and pigs were analyzed under validated conditions. Results: The optimal performance was achieved using 10⁵ genomic copies/mL of the antigen coating and a 5% BSA blocking agent. The assay showed strong diagnostic accuracy (AUC = 0.97), reproducibility (CVs < 5%), and linearity (R² = 0.9890). Specificity tests with PCV2a, PCV2b, and PRRSV showed minimal cross-reactivity (<7%). The cross-species comparison revealed a positive correlation (R² = 0.1815) and acceptable agreement (bias = −0.21) between guinea pig and porcine sera. The validated cut-off (S/P = 0.4) enabled accurate classification across both species and aligned well with commercial kits. Conclusions: The in-house ELISA offers a robust, reproducible, and scientifically validated platform for immunogenicity verification, supporting its application in Korea’s national lot-release system. Homologous competition assays with PCV2d are planned to further confirm antigen specificity. Full article

(This article belongs to the Special Issue Animal Diseases: Immune Response and Vaccines)

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12 pages, 649 KiB

Open AccessReview

Melanoma Vaccines: Comparing Novel Adjuvant Treatments in High-Risk Patients

by Joseph C. Broderick, Alexandra M. Adams, Elizabeth L. Barbera, Spencer Van Decar, Guy T. Clifton and George E. Peoples

Vaccines 2025, 13(6), 656; https://doi.org/10.3390/vaccines13060656 - 19 Jun 2025

Viewed by 392

Abstract

Background: The emergence of checkpoint inhibitors (CPIs) has significantly improved survival outcomes in later-stage melanoma. However, the efficacy of these treatments remains limited, with around 50% of later-stage melanoma patients experiencing recurrence. As variable response rates to CPIs persist, the development of cancer [...] Read more.

Background: The emergence of checkpoint inhibitors (CPIs) has significantly improved survival outcomes in later-stage melanoma. However, the efficacy of these treatments remains limited, with around 50% of later-stage melanoma patients experiencing recurrence. As variable response rates to CPIs persist, the development of cancer vaccines has emerged as a potential strategy to augment antitumor immune responses. Results: This review compares two promising personalized therapeutic cancer vaccine trials in advanced melanoma: Elios Therapeutics’ Tumor Lysate (TL) vaccine and Moderna’s mRNA-4157 vaccine. The TL vaccine, which utilizes yeast cell wall particles (YCWPs) loaded with autologous tumor lysate, and the mRNA-4157 vaccine, which encodes up to 34 patient-specific neoantigens, both aim to stimulate robust tumor-specific immune responses. Both trials were phase 2b randomized studies, with Elios Therapeutics’ trial employing a double-blind, placebo-controlled design, while Moderna’s was open-label. Both trials had roughly equivalent sample sizes (n = 187 and n = 157, respectively) with similar demographics and disease characteristics. The TL trial reported improvements in disease-free survival (DFS) with a hazard ratio (HR) of 0.52 (p < 0.01) over 36 months, whereas the mRNA-4157 trial demonstrated improvements in recurrence-free survival (RFS) with an HR of 0.56 (p = 0.053) over 18 months. The TL vaccine exhibited lower rates of related grade 3 adverse events (<1%) compared to the mRNA vaccine (12%). Key differences between the two trials include the use of CPIs, with 100% of patients in the mRNA trial receiving pembrolizumab versus 37% of the patients in the TL trial receiving either an anti-PD-1 or anti-CTLA-4. The production processes also varied significantly, with the mRNA vaccine requiring individualized sequencing and a 9-week production time, while the TL vaccine utilized tumor lysate with a 1–3-day production time. Conclusions: While both vaccines demonstrated promising efficacy, future phase 3 trials are needed to further evaluate their potential as adjuvant therapies for melanoma. This review highlights the comparative strengths and limitations of these vaccine platforms, providing insight into the evolving landscape of adjuvant cancer vaccines. Full article

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

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14 pages, 1700 KiB

Open AccessArticle

Delayed Viral Clearance Accompanied by Early Impaired Humoral and Virus-Specific T-Cell Response in Patients with Coronavirus Disease 2019 and Interstitial Lung Disease

by Jiaying Zhong, Juan Li, Rui Wei, Bingpeng Guo, Tingting Cui, Peiyu Huang, Zhongfang Wang, Qun Luo and Qian Han

Vaccines 2025, 13(6), 655; https://doi.org/10.3390/vaccines13060655 - 19 Jun 2025

Viewed by 316

Abstract

Objectives: Patients with interstitial lung disease (ILD) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are at high risk of severe coronavirus disease 2019. It is unclear whether anti-viral cellular and humoral immunity is impacted in patients with ILD in the presence [...] Read more.

Objectives: Patients with interstitial lung disease (ILD) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are at high risk of severe coronavirus disease 2019. It is unclear whether anti-viral cellular and humoral immunity is impacted in patients with ILD in the presence of immune disorders and immunosuppressive therapy. This results in poor control of viral infections following SARS-CoV-2 infection. We aimed to highlight the clinical management of patients with ILD with regard to the adjustment of anti-inflammatory therapy during SARS-CoV-2 infection. Methods: We compared viral clearance, antibody levels, and T-cell immune response between healthy controls and patients with connective tissue disease-related ILD (CTD-ILD) or interstitial pneumonia with autoimmune features (IPAF). Results: Patients with ILD exhibited a higher viral load than the control group (1.58 × 10⁶ vs. 2.37 × 10³ copies/mL, p = 0.018), as well as a significantly lower level of neutralizing antibodies against the wild-type (WT) virus (7.01 vs. 625.6, p < 0.0001) and Omicron BA.5 (7.19 vs. 128.4, p < 0.001). Similarly, a lower virus-specific T-cell (VST) immune response was observed 14 days post-symptom onset in the ILD group (CD4⁺ VSTs: 0.018 vs. 0.082, p = 0.005; CD8⁺ VSTs: 0.0008 vs. 0.047, p = 0.004). The ILD group had no other heightened inflammatory biomarkers compared with the control group. Conclusions: Our study provides novel evidence of the underlying interaction between virus clearance and host immune status and sheds light on the clinical management of patients with ILD with regard to the adjustment of anti-inflammatory therapy during SARS-CoV-2 infection. Full article

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

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21 pages, 2202 KiB

Open AccessReview

CAR Beyond αβ T Cells: Unleashing NK Cells, Macrophages, and γδ T Lymphocytes Against Solid Tumors

by Yunjia Xian and Lu Wen

Vaccines 2025, 13(6), 654; https://doi.org/10.3390/vaccines13060654 - 19 Jun 2025

Viewed by 484

Abstract

Chimeric antigen receptor (CAR)-engineered cell therapy represents a landmark advancement in cancer immunotherapy. While αβ CAR-T therapy has demonstrated remarkable success in hematological malignancies, its efficacy in solid tumors remains constrained mainly by factors such as antigen heterogeneity, immunosuppressive microenvironments, and on-target/off-tumor toxicity. [...] Read more.

Chimeric antigen receptor (CAR)-engineered cell therapy represents a landmark advancement in cancer immunotherapy. While αβ CAR-T therapy has demonstrated remarkable success in hematological malignancies, its efficacy in solid tumors remains constrained mainly by factors such as antigen heterogeneity, immunosuppressive microenvironments, and on-target/off-tumor toxicity. To overcome these limitations, emerging CAR platforms that utilize alternative immune effectors, including natural killer (NK) cells, macrophages, and γδ T lymphocytes, are rapidly gaining traction. This review systematically analyzes the mechanistic advantages of CAR-NK, CAR-M, and CAR-γδ T cell therapies, while critically evaluating persistent challenges in clinical translation, including limited cell persistence, manufacturing scalability, and dynamic immune evasion mechanisms. We further discuss innovative strategies to enhance therapeutic efficacy through some viable strategies. By bridging fundamental immunology with translational engineering, this work provides a roadmap for developing CAR therapies capable of addressing the complexities of solid tumor eradication. Full article

(This article belongs to the Special Issue Vaccination or Infection and the Role of T Cells—the Response to Cancer, Autoimmunity or Inflammatory Diseases)

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Graphical abstract

26 pages, 1458 KiB

Open AccessReview

Innovation in mRNA Vaccines and RNAi via Protein Nanocages

by Sohrab Ahmadivand

Vaccines 2025, 13(6), 653; https://doi.org/10.3390/vaccines13060653 - 18 Jun 2025

Viewed by 554

Abstract

Self-assembling protein nanocages (SAPNs) are distinct natural structures formed by the self-assembly of identical subunits, providing a highly efficient platform and a novel strategy for vaccine development and RNAi therapy. Their internal cavity allows for precise cargo encapsulation, while the externally modifiable surface [...] Read more.

Self-assembling protein nanocages (SAPNs) are distinct natural structures formed by the self-assembly of identical subunits, providing a highly efficient platform and a novel strategy for vaccine development and RNAi therapy. Their internal cavity allows for precise cargo encapsulation, while the externally modifiable surface supports multivalent antigen presentation, thereby enhancing stability, targeted delivery, and immune activation. In addition to serving as stable subunit vaccines with multivalent antigen display, SAPNs can be incorporated into mRNA vaccines (SAPN-RNA vaccines) by pre-fusing with the antigen. This strategy stabilizes secreted antigenic proteins with prolonged presentation to the immune system, and improves vaccine efficacy while reducing off-target effects and minimizing required doses. Additionally, SAPNs can overcome cellular uptake barriers, enhance DNA vaccine efficacy, and enable the co-delivery of antigens and adjuvants. Functionalization with adjuvants or targeting ligands further improves their immunostimulatory properties and specificity. The SAPN-RNAi strategy optimizes siRNA delivery by promoting lysosomal escape, enhancing targeted uptake, and protecting siRNA from degradation through SAPN encapsulation. This review examines the structural and functional properties of protein nanocages and their applications in vaccine design and RNAi delivery, emphasizing their synergistic effects, and exploring current progress, challenges, and future directions. In conclusion, SAPNs represent a versatile multifunctional platform with broad applicability across subunit, mRNA and DNA vaccines, adjuvant co-delivery, and RNAi therapeutics, with significant potential against viral infections. Full article

(This article belongs to the Collection Advance in Nanoparticles as Vaccine Adjuvants)

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16 pages, 1678 KiB

Open AccessArticle

Herd Immunity to the Measles, Mumps and Rubella Viruses Among the Belgradian Population in May, 2024

by Anna Y. Popova, Vyacheslav S. Smirnov, Svetlana A. Egorova, Luka Dragačević, Angelica M. Milichkina, Jelena Protić, Ekaterina M. Danilova, Irina V. Drozd, Marija Petrušić, Ojuna B. Zhimbaeva, Elizaveta S. Glazkova, Nataša Gutić, Valeri A. Ivanov, Edward S. Ramsay, Oleg V. Kotsar, Vyacheslav Y. Smolensky and Areg A. Totolian

Vaccines 2025, 13(6), 652; https://doi.org/10.3390/vaccines13060652 - 18 Jun 2025

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Abstract

Background/Objectives: In the Republic of Serbia, measles vaccination was first introduced in 1971, while combined vaccination (measles, mumps, rubella) was made mandatory in 1996 as part of the national vaccination program. Reported prevalence values for 2023 were <0.75 cases per 100K population for [...] Read more.

Background/Objectives: In the Republic of Serbia, measles vaccination was first introduced in 1971, while combined vaccination (measles, mumps, rubella) was made mandatory in 1996 as part of the national vaccination program. Reported prevalence values for 2023 were <0.75 cases per 100K population for measles, 0.09 cases per 100K for mumps, and no cases of rubella. Methods: This cross-sectional study was performed in May, 2024 as part of the project “Herd Immunity to Vaccine-Preventable and Other Relevant Infections in the Belgradian Population.” It focused on assessing herd immunity to measles, mumps and rubella (MMR) among residents insofar as these remain a public concern despite the availability of vaccines. A total of 2533 subjects were distributed across nine age groups, covering those aged 1–70⁺ years and various professional groups residing in Belgrade. Participants were stratified by age and activity. Upon obtaining individual information by online questionnaire and receiving a signed statement of informed consent, blood samples were obtained for IgG antibody testing (ELISA) to determine MMR serological status. The results were compared to national and international immunization standards to evaluate herd immunity levels. Results: Our results indicate varying levels of immunity for each virus, with specific demographic groups showing different immunity levels. Total measles seroprevalence during this study was 74.7%, with significant variation across all age groups. While high seropositivity was observed in both children (90.7%) and elder age groups (98.4%), middle-aged individuals in the age group 30–49 years showed significantly lower IgG levels. Between 2021 and 2023, there were no registered cases of rubella detected in Serbia, which indicates a high level of immunity. This was confirmed here with consistently high IgG levels across all age groups, with an average seropositivity of 94.8%. Average mumps seropositivity across all age groups was 85.1%. The lowest value was in the young child (1–5 years) age group (76.1%); the highest was in the elderly group (92.6%). Conclusions: The current findings suggest that the Belgradian population has strong overall immunity to MMR, yet with some concerns regarding measles immunity in middle-aged adults, suggesting a potential need for catch-up vaccinations. While rubella status indicates strong herd immunity and minimal risk of outbreaks, mumps immunity in some groups (children, middle-aged adults) is below the protective threshold. While it is still sufficient to prevent widespread transmission, it should be closely observed. To our knowledge, this study is the first of its kind to provide data about MMR seroprevalence in Belgrade. Findings indicate the need for constant surveillance and revaccination of vulnerable/seronegative groups. Full article

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

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11 pages, 556 KiB

Open AccessCommunication

Real-World Impact of Pneumococcal Conjugate Vaccines on Vaccine Serotypes and Potential Cross-Reacting Non-Vaccine Serotypes

by Kevin Apodaca, Lindsay R. Grant, Johnna Perdrizet, Derek Daigle, Gabriel Mircus and Bradford D. Gessner

Vaccines 2025, 13(6), 651; https://doi.org/10.3390/vaccines13060651 - 17 Jun 2025

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Abstract

Background: Clinical trials and serological studies have demonstrated that vaccine-induced antibodies can cross-react with some non-vaccine serotypes. However, there are limited longitudinal data on the impact of pneumococcal conjugate vaccines (PCV) on cross-reactive serotypes after implementation in immunization programs. This study examines the [...] Read more.

Background: Clinical trials and serological studies have demonstrated that vaccine-induced antibodies can cross-react with some non-vaccine serotypes. However, there are limited longitudinal data on the impact of pneumococcal conjugate vaccines (PCV) on cross-reactive serotypes after implementation in immunization programs. This study examines the impact of PCVs on pneumococcal disease cases due to potential cross-reactive serotypes. Methods: Eleven countries with serotyped invasive pneumococcal disease (IPD) surveillance data that had introduced PCV10 or PCV13 were identified. The analysis focused on IPD cases due to serotypes included in PCV10 and PCV13 (PCV10/13 VTs: 6B, 9V, 19F, 23F; PCV13 only VTs: 6A, 19A) and to vaccine-related serotypes (VRTs: 6C, 9N, 23A, 23B) that may be immunologically related to VTs in children under 5 years old. For each country, the number of IPD cases were charted over time according to serogroup. Results: Following PCV introduction, reductions in VT IPD cases were observed in all countries, while some VRT IPD cases remained unchanged or increased. Serotype 19A cases declined in PCV13 countries but increased in countries that introduced PCV10. VRT 6C cases rose in PCV10 countries but showed minimal change in PCV13 countries. In PCV13 countries, 9N cases remained unchanged while 23A and 23B experienced modest increases. Conclusions: The inclusion of VT 19A in PCV13, but not in PCV10, may account for the significant increase in VRT 19A cases in PCV10 countries. The slight change in VRT 6C cases in PCV13 countries compared to the significant rise in PCV10 countries suggests that PCV13 provides cross-protection for serotype 6C through serotype 6A. Cross-protection could not be determined for other VRTs, as their cases increased or remained unchanged or had insufficient data for evaluation. Full article

(This article belongs to the Section Vaccines against Infectious Diseases)

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15 pages, 421 KiB

Open AccessReview

VITT Pathophysiology: An Update

by Eleonora Petito and Paolo Gresele

Vaccines 2025, 13(6), 650; https://doi.org/10.3390/vaccines13060650 - 17 Jun 2025

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Abstract

Vaccine-induced thrombotic thrombocytopenia (VITT) is a rare thrombotic disorder first identified in 2021 as a catastrophic syndrome associated with anti-SARS-CoV-2 adenoviral vector (AdV)-vaccine administration. It is characterized by the presence of oligo- or monoclonal anti-PF4 antibodies able to induce in vitro platelet activation [...] Read more.

Vaccine-induced thrombotic thrombocytopenia (VITT) is a rare thrombotic disorder first identified in 2021 as a catastrophic syndrome associated with anti-SARS-CoV-2 adenoviral vector (AdV)-vaccine administration. It is characterized by the presence of oligo- or monoclonal anti-PF4 antibodies able to induce in vitro platelet activation in the presence of PF4. In addition to this immune-based pathomechanism, random splicing events of the Adv-vector DNA encoding for SARS-CoV-2 spike protein resulting in the secretion of soluble spike variants have been postulated as a possible pathophysiological mechanism. More recently, some novel clinical-pathological anti-PF4-associated entities also characterized by thrombosis, thrombocytopenia, and VITT-like antibodies but independent from heparin or AdV-vaccine administration have been identified. To date, these VITT-like disorders have been reported following the administration of vaccines different from anti-SARS-CoV-2 AdV-vaccines, like human papillomavirus (HPV) and mRNA-based COVID-19 vaccines, following a bacterial or viral respiratory infection, and in patients with a monoclonal gammopathy of undetermined significance. The purpose of this review is to provide an update on the knowledge on VITT pathogenesis, focusing on recent findings on anti-PF4 antibodies, on a possible genetic predisposition to VITT, on VITT-antibody intracellular activated pathways, on lipid metabolism alterations, and on new VITT-like disorders. Full article

(This article belongs to the Special Issue Vaccine-Induced Immune Thrombotic Thrombocytopenia)

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14 pages, 233 KiB

Open AccessEditorial

Expanded Programme on Immunization (EPI): A Legacy of 50 Years and the Road Ahead

by Imran Mirza, Ephrem Tekle Lemango and Ann Lindstrand

Vaccines 2025, 13(6), 649; https://doi.org/10.3390/vaccines13060649 - 17 Jun 2025

Viewed by 487

Abstract

Throughout history, disease and epidemics have shaped human survival [...] Full article

(This article belongs to the Special Issue 50 Years of Immunization—Steps Forward)

25 pages, 1908 KiB

Open AccessArticle

SARS-CoV-2 Receptor Binding Domain (RBD) Protein–Protein Conjugate Induces Similar or Better Antibody Responses as Spike mRNA in Rhesus Macaques

by Puthupparampil V. Scaria, Christopher G. Rowe, Ivan Kosik, Zhe Hu, Jonathan P. Renn, Nada Alani, Pinar Kemanli, Sachy Orr-Gonzalez, Lynn E. Lambert, Kayode Adeyemi, Justin Y. A. Doritchamou, Emma K. Barnafo, Kelly M. Rausch, Liya Muslinkina, Robert D. Morrison, John-Paul Todd, Dominic Esposito, Andrew Lees, Jonathan Yewdell and Patrick E. Duffy

Vaccines 2025, 13(6), 648; https://doi.org/10.3390/vaccines13060648 - 17 Jun 2025

Viewed by 507

Abstract

Background/Objectives: Rapid development of vaccines against SARS-CoV-2 was pivotal to controlling the COVID-19 pandemic. The emergency also provided a rare opportunity to test novel vaccine platforms such as mRNA in large clinical trials. Most of the early vaccines used SARS-CoV-2 Spike protein [...] Read more.

Background/Objectives: Rapid development of vaccines against SARS-CoV-2 was pivotal to controlling the COVID-19 pandemic. The emergency also provided a rare opportunity to test novel vaccine platforms such as mRNA in large clinical trials. Most of the early vaccines used SARS-CoV-2 Spike protein as the target antigen. Nevertheless, subsequent studies have shown that Receptor Binding Domain (RBD) of Spike also can yield efficacious vaccines, and we previously demonstrated that chemical conjugation of RBD to a carrier protein, EcoCRM^®, enhanced antibody responses and induced strong virus neutralization activity in mice. Methods: Here, we compared the immunogenicity of this conjugate to that of an approved mRNA vaccine from Pfizer/BioNTech in rhesus macaques over a period of nine months. Results: AS01-adjuvanted RBD conjugate induced a similar or better antibody response, receptor binding inhibition, and virus neutralization activity against different variants of SARS-CoV-2, compared to mRNA. IgG subclass profiles induced by conjugate and mRNA vaccines were initially dominated by IgG1 and IgG3 then switched to IgG2 and IgG4 dominant profiles during the subsequent six-month period. Polyclonal immune sera from the conjugate and mRNA had similar antibody avidity at multiple time points. Conclusions: In summary, antibody responses in rhesus macaques induced by the RBD-EcoCRM conjugate and the Spike mRNA vaccine are very similar. These results demonstrate the potential for the RBD-EcoCRM conjugate as a vaccine against SARS-CoV-2. Full article

(This article belongs to the Special Issue Receptor-Binding Domain-Based Vaccines Against SARS-CoV-2)

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13 pages, 668 KiB

Open AccessArticle

Troubled Times, Changing Tides: A Seroprevalence Study on Meningococcal Immunity in France Between 2016 and 2024

by Samy Taha, Aude Terrade, Oumar Doucoure, Ala-Eddine Deghmane and Muhamed-Kheir Taha

Vaccines 2025, 13(6), 647; https://doi.org/10.3390/vaccines13060647 - 16 Jun 2025

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Abstract

Background/Objectives: In France, non-pharmaceutical interventions (NPIs) implemented to control COVID-19 led to a significant decline in invasive meningococcal disease (IMD) cases. However, a rebound in cases, particularly for serogroups W and Y, was observed after the gradual lifting of NPIs, raising questions about [...] Read more.

Background/Objectives: In France, non-pharmaceutical interventions (NPIs) implemented to control COVID-19 led to a significant decline in invasive meningococcal disease (IMD) cases. However, a rebound in cases, particularly for serogroups W and Y, was observed after the gradual lifting of NPIs, raising questions about an “immunity gap” due to reduced circulation of the bacteria. During the study period, vaccination against MenC was mandatory from 2018, and vaccination against MenB has been recommended since 2022. Methods: We conducted a retrospective seroepidemiological study using 166 normal sera collected between 2016 and 2024. Anti-Neisseria meningitidis IgG levels were quantified by ELISA using purified capsular polysaccharides for serogroups B, C, W, Y, and X. Samples were categorized into three periods: pre-NPIs (n = 72), during NPIs (n = 33), and post-NPIs (n = 61). Statistical comparisons were performed using Kruskal–Wallis tests for non-parametric data. Results: Our results show a significant decline in anti-serogroup B IgG antibody levels after the lifting of NPIs (p < 0.0001) in line with reduced circulation. Anti-serogroup C IgG antibody levels increased incrementally (p = 0.0003), particularly in those aged 1–4 years, likely reflecting a catch-up in anti-meningococcal C vaccination coverage. Anti-serogroup W IgG antibody levels remained stable, suggesting sustained circulation, but shifted to young children in the post-NPI period, potentially due to a genotypic shift. Anti-serogroup Y IgG antibody levels transiently increased significantly (p < 0.0001) during the NPI period but then decreased back after their lifting. Anti-serogroup X IgG antibody levels remained stable, consistent with its low prevalence and the absence of targeted vaccination. Full article

(This article belongs to the Section Vaccines against Tropical and other Infectious Diseases)

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7 pages, 158 KiB

Open AccessCommentary

Strengthening National Regulatory Authorities in Africa: A Critical Step Towards Enhancing Local Manufacturing of Vaccines and Health Products

by Alemayehu Duga, Nebiyu Dereje, Mosoka Papa Fallah, Tedi Angasa, Abebe Genetu Bayih, Edinam Agbenu, Ngashi Ngongo, Raji Tajudeen and Jean Kaseya

Vaccines 2025, 13(6), 646; https://doi.org/10.3390/vaccines13060646 - 16 Jun 2025

Viewed by 548

Abstract

The World Health Organization (WHO) Global Benchmarking Tool (GBT) classifies regulatory systems into four maturity levels, with Maturity Level 3 (ML3) signifying a stable and effective regulatory environment. As of January 2025, eight African nations—Egypt, Ghana, Nigeria, Rwanda, Senegal, South Africa, Tanzania, and [...] Read more.

The World Health Organization (WHO) Global Benchmarking Tool (GBT) classifies regulatory systems into four maturity levels, with Maturity Level 3 (ML3) signifying a stable and effective regulatory environment. As of January 2025, eight African nations—Egypt, Ghana, Nigeria, Rwanda, Senegal, South Africa, Tanzania, and Zimbabwe—have attained ML3 status, marking a significant milestone in the continent’s regulatory landscape. Achieving ML3 confers critical benefits, including reducing substandard and falsified medicines, which enhances public health safety and fosters trust in healthcare systems. This progress encourages local manufacturing, diminishing reliance on imported medicines and promoting economic development. Furthermore, ML3 NRAs are better equipped to address public health emergencies, enabling swift approvals for vaccines and therapeutics while upholding safety standards. Nonetheless, challenges persist, including fragmented regulatory systems, the prevalence of counterfeit medicines, and limited resources. Overcoming these hurdles necessitates enhanced organizational capacity, investments in training, and the promotion of collaboration among NRAs. There is an urgent call for greater political commitment and resource allocation to strengthen regulatory systems across Africa. Achieving and maintaining ML3 status is essential for enhancing medicine regulation, supporting local manufacturing, and improving public health outcomes across the continent. While progress has been made, sustained efforts are crucial to tackling existing challenges and harnessing the full potential of advanced regulatory frameworks. Full article

(This article belongs to the Special Issue Challenges to Developing New Vaccines and Improving Existing Platforms)

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Open AccessArticle

A Promising Attenuated Rhabdovirus Vaccine Candidate Conferring Dual-Route Protection Against MSRV Disease in Largemouth Bass (Micropterus salmoides)

by Xiaozhe Fu, Wenxian Li, Minghui Kong, Hongru Liang, Qiang Lin, Yinjie Niu, Xia Luo, Baofu Ma, Jin Zhou and Ningqiu Li

Vaccines 2025, 13(6), 645; https://doi.org/10.3390/vaccines13060645 - 16 Jun 2025

Viewed by 319

Abstract

Background/Objectives: Largemouth bass rhabdovirus (Micropterus salmoides rhabdovirus, MSRV) disease causes high mortality in largemouth bass farming. Therefore, vaccine development is critical for largemouth bass prevention against MSRV. Methods: An attenuated strain, denoted as MSRV-0509, was selected through intraperitoneal injection and immersion challenge [...] Read more.

Background/Objectives: Largemouth bass rhabdovirus (Micropterus salmoides rhabdovirus, MSRV) disease causes high mortality in largemouth bass farming. Therefore, vaccine development is critical for largemouth bass prevention against MSRV. Methods: An attenuated strain, denoted as MSRV-0509, was selected through intraperitoneal injection and immersion challenge assays, followed by plaque purification. The biological characteristics of MSRV-0509, including optimal inoculation dose, replication kinetics, thermostability, pH resistance, chloroform tolerance, and storage viability, were determined via viral titration. Spatiotemporal distribution patterns in largemouth bass post-intraperitoneal injection or immersion infection were quantified by qPCR. Immunoprotective efficacy was evaluated through intraperitoneal and immersion vaccination. Mechanistic insights were explored via relative qPCR and serum neutralization assays. Safety was assessed by single-dose overdose immunization and virulence reversion experiments. Results: An attenuated strain MSRV-0509 was screened through a challenge assay, exhibiting complete avirulence in largemouth bass compared to the virulent strain SCRV-T6. MSRV-0509 demonstrated optimal replication at low MOI (0.0001) in CPB cells, with peak titers (10^8.3 TCID₅₀/mL) at 96 h post-infection. The virus showed susceptibility to high temperatures, lipid solvents and acidic conditions, with prolonged stable storage viability at −80 °C. Tissue distribution revealed the spleen as the primary target after intraperitoneal injection, while immersion restricted infection to gills, with rapid clearance by 3–6 dpi. Vaccination trials identified 5 × 10² TCID₅₀/fish via intraperitoneal injection and 10^6.0 TCID₅₀/mL via immersion as effective immunizing doses, providing 100% relative survival post-challenge. Immune gene expression and serum neutralization showed Th1 and Th2 activation via intraperitoneal injection (elevated IL-12, IFN-γ, IL-10, IgM), whereas only the Th1 response was activated after vaccine immersion. No abnormality and mortality were observed in single overdose vaccination and virulence reversion experiments, confirming that MSRV-0509 was safe. Conclusions: These results proved that MSRV-0509 could be a promising vaccine candidate to protect largemouth bass from MSRV disease. Full article

(This article belongs to the Section Veterinary Vaccines)

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14 pages, 651 KiB

Open AccessArticle

Safety and Efficacy of Simultaneous Vaccination with Polysaccharide Conjugate Vaccines Against Pneumococcal (13-Valent Vaccine) and Haemophilus Type B Infections in Children with Systemic Juvenile Idiopathic Arthritis: Prospective Cohort Study

by Ekaterina Alexeeva, Tatyana Dvoryakovskaya, Dmitry Kudlay, Anna Fetisova, Ivan Kriulin, Elizaveta Krekhova, Anna Kabanova, Vladimir Labinov, Elizaveta Labinova and Mikhail Kostik

Vaccines 2025, 13(6), 644; https://doi.org/10.3390/vaccines13060644 - 15 Jun 2025

Viewed by 445

Abstract

Background: The introduction of biological drugs into clinical practice for the treatment of children with systemic juvenile idiopathic arthritis (sJIA) allows disease control but increases the risk of infectious events. Infectious events cause immunosuppressive therapy interruptions, leading to disease flare and life-threatening [...] Read more.

Background: The introduction of biological drugs into clinical practice for the treatment of children with systemic juvenile idiopathic arthritis (sJIA) allows disease control but increases the risk of infectious events. Infectious events cause immunosuppressive therapy interruptions, leading to disease flare and life-threatening complications, namely macrophage activation syndrome. Our study aimed to evaluate the efficacy and safety of simultaneous vaccination against pneumococcal and Haemophilus influenzae type b (Hib) in children with sJIA. Methods: This study included 100 sJIA patients receiving immunosuppressive therapy who were simultaneously vaccinated against pneumococcal and Haemophilus influenzae type b (Hib) infections. The mean age of disease onset was 5.5 years. The median age at vaccination was 10 ± 4.5 years. Clinical and laboratory parameters of sJIA activity, immunization efficacy, and safety, including anti-SP and anti-Hib IgG antibodies, as well as all vaccination-related adverse events (AEs), were recorded in every patient before, 3 weeks after, and 6 months after vaccination. Results: At the time of vaccination, 29% of patients did not meet the criteria for the inactive disease stage, as defined by C. Wallace: active joints were present in 34.5% of patients, systemic manifestations (rash and/or fever) were present in 41.3%, and 24.2% of patients had solely inflammatory laboratory activity. The protective titer of anti-SP and anti-Hib IgG antibodies was detected in the majority of patients 3 weeks after vaccination (100% and 93%, respectively). The results remained unchanged (99% and 92%, respectively) for 6 months of follow-up, compared to the baseline (91% and 37%, p = 0.000001). Anti-SP IgG and anti-Hib titers raised from 48.3 (18.2; 76.5) and 0.64 (0.3; 3.2) U/mL at the baseline to 103.5 (47.3; 185.4) and 4 (3.5; 4.2) U/mL at D22 and 105 (48.7; 171.8) and 4 (3.8; 4) U/mL (EOS), respectively. Immunosuppressive therapy regimens (combined therapy or biological disease-modifying antirheumatic drug monotherapy) did not influence the immunogenic efficacy of vaccination. The incidence of infectious complications (p = 0.0000001) and antibiotic prescriptions (p = 0.0000001) decreased by more than two times, to 29.9 and 13.8 events per 100 patient months, respectively, within 6 months after vaccination—the average duration of acute infectious events was reduced by five times after immunization (p = 0.0000001). Vaccination did not lead to disease flare: the number of patients with active joints decreased by half compared to the baseline, and the number of patients with systemic manifestations decreased by six times. All vaccine-associated adverse events were considered mild and resolved within 1–2 days. Conclusions: Simultaneous vaccination against pneumococcal and Hib infections in sJIA children is an effective and safe tool that reduces the number and duration of infectious events and does not cause disease flare-ups. Full article

(This article belongs to the Special Issue Pneumococcal Vaccines: Current Status and Future Prospects)

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15 pages, 2870 KiB

Open AccessSystematic Review

Immunogenicity and Safety of Pneumococcal Vaccines Co-Administered with Common Travel Vaccines in Adults: A Systematic Review

by Raziyeh Niyati, Omid Rezahosseini, Christina Ekenberg, Carsten Schade Larsen and Zitta Barrella Harboe

Vaccines 2025, 13(6), 643; https://doi.org/10.3390/vaccines13060643 - 14 Jun 2025

Viewed by 419

Abstract

Background: Co-administration of vaccines can impact the immune response and safety. We aim to systematically review the current scientific literature and find evidence regarding the immunogenicity and safety of pneumococcal vaccines co-administered with common vaccines that are recommended for travelers, including hepatitis A, [...] Read more.

Background: Co-administration of vaccines can impact the immune response and safety. We aim to systematically review the current scientific literature and find evidence regarding the immunogenicity and safety of pneumococcal vaccines co-administered with common vaccines that are recommended for travelers, including hepatitis A, hepatitis B, yellow fever, tetanus, diphtheria, and acellular pertussis (Tdap), Japanese encephalitis, rabies, typhoid, or meningococcal (MCV) vaccine in adults (18 years or older). Methods: We followed the PRISMA 2020 guidelines and used the PICOS process to select the keywords. We searched PubMed, Web of Science, Scopus, EMBASE, and Google from 1 January 2000 to 30 June 2024. We included randomized controlled trials, non-randomized controlled trials, observational studies, case series, and case reports in adults, all published in English. Results: Out of 598 articles screened, 6 studies were included in our study. Three studies involved immunocompetent individuals, and three involved immunocompromised individuals. Co-administration of pneumococcal vaccine with Tdap or Hepatitis A in immunocompetent individuals was safe and immunogenic. Similar findings were reported for immunocompromised individuals when pneumococcal vaccines were co-administered with Tdap, hepatitis A, and hepatitis B. However, no reports investigated the co-administration of yellow fever, rabies, Japanese encephalitis, and typhoid. Two non-randomized studies in immunocompromised individuals had a high risk of bias. Conclusions: The studies collectively indicate that the co-administration of pneumococcal vaccines with Hepatitis A and Tdap vaccines in adult immunocompetent and immunocompromised individuals is safe and immunogenic. However, a knowledge gap remains, and further high-quality studies are needed, particularly due to the limited number of studies and the potential risk of bias. Full article

(This article belongs to the Section Vaccine Advancement, Efficacy and Safety)

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13 pages, 499 KiB

Open AccessArticle

Public Health Impact of Potential Infant MenACWY Vaccination Strategies in Spain

by Katharina Schley, Jamie Findlow, Carlos Molina, Shannon M. Sullivan and Eszter Tichy

Vaccines 2025, 13(6), 642; https://doi.org/10.3390/vaccines13060642 - 13 Jun 2025

Viewed by 419

Abstract

Background: The Spanish Interterritorial Council of the National Health System (a central government body) currently recommends vaccination against meningococcal serogroup C (MenC) at 4 and 12 months of age for prevention of invasive meningococcal disease (IMD). The Advisory Committee on Vaccines of the [...] Read more.

Background: The Spanish Interterritorial Council of the National Health System (a central government body) currently recommends vaccination against meningococcal serogroup C (MenC) at 4 and 12 months of age for prevention of invasive meningococcal disease (IMD). The Advisory Committee on Vaccines of the Spanish Association of Pediatrics (a professional medical association) and numerous Spanish regional bodies instead recommend quadrivalent vaccination against serogroups A, C, W, and Y (MenACWY) at 4 and 12 months of age. The central government and Spanish Association of Pediatrics also recommend MenACWY vaccination at 12 years of age. This study assessed the potential public health effects of replacing the MenC vaccination schedule with different MenACWY vaccination schedules in infants. Methods: Here, a static multi-cohort population model was used to evaluate potential effects on public health of IMD due to meningococcal serogroups C/W/Y, comparing MenC infant vaccination (reference strategy) against four different strategies including quadrivalent tetanus toxoid conjugate vaccine (MenACWY-TT; Nimenrix^®, Pfizer Europe MA EEIG, Brussels, Belgium) infant vaccination; all strategies included MenACWY-TT vaccination at 12 years of age. Results: The most effective strategy for infant vaccination was MenACWY-TT at 2, 4, and 12 months, preventing an estimated additional 103 IMD cases, 17 deaths, and 41 cases with long-term sequelae (LTS) versus the reference strategy in the base-case IMD incidence scenario. When strategies included a two-dose infant schedule, the earlier the infant MenACWY-TT vaccine was administered, the more additional cases, deaths, and cases with LTS were prevented (base-case and high-incidence scenarios). Conclusions: This analysis supports implementation of MenACWY-TT as a replacement for MenC vaccination. Full article

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

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14 pages, 2294 KiB

Open AccessArticle

Spatiotemporal Epidemiology of Lumpy Skin Disease and Evaluation of the Heterologous Goatpox Vaccine: Insights into Immunogenicity and Impact

by Manjunatha Reddy Gundallahalli Bayyappa, Sai Mounica Pabbineedi, Sudeep Nagaraj, Shraddha Bijalwan, Sunil Tadakod, Chandana Ramesh Uma, Sanjay Pawar, Pathan Yahaya Khan, Vijay Kumar Teotia and Baldev Raj Gulati

Vaccines 2025, 13(6), 641; https://doi.org/10.3390/vaccines13060641 - 13 Jun 2025

Viewed by 483

Abstract

Background: Lumpy skin disease (LSD) is major transboundary disease affecting cattle and water buffaloes, indirectly causing huge socio-economic losses. Following its first outbreak in India in 2019, the heterologous Goatpox (Uttarkashi strain) vaccine mitigated LSD. Objective: Due to limited data on the spatiotemporal [...] Read more.

Background: Lumpy skin disease (LSD) is major transboundary disease affecting cattle and water buffaloes, indirectly causing huge socio-economic losses. Following its first outbreak in India in 2019, the heterologous Goatpox (Uttarkashi strain) vaccine mitigated LSD. Objective: Due to limited data on the spatiotemporal distribution of the disease, this study investigates its dynamics and presents findings from a field study conducted in Maharashtra, India. This study evaluates the safety, immunogenicity, and duration of immunity provided by a heterologous vaccine. Additionally, it examines post-vaccination responses in relation to factors such as age, gender, and breed. Methods: This study employed spatiotemporal analysis of lumpy skin disease (LSD) outbreaks from 2020 to 2024 using GeoDa (v1.22), incorporating Moran’s I and Getis-Ord Gi* statistics to identify spatial clustering patterns. A randomized field trial was conducted to evaluate vaccine safety and immunogenicity in 657 cattle across seven districts. Humoral immune responses were assessed using the serum neutralization test (SNT) and indirect enzyme-linked immunosorbent assay (ELISA), while cell-mediated immunity was evaluated via Interferon-gamma (IFN-γ) ELISA. For sero-monitoring, a total of 1925 serum samples from 22 districts were analyzed. Additionally, statistical analyses (n = 1925), including the Kappa Index, ANOVA, and logistic regression, were performed using SPSS v27 to investigate the influence of factors such as age, sex, and breed (significance level: p < 0.05). Results: LSD exhibited significant spatial clustering across Maharashtra. The Goatpox vaccine was 100% safe, with no adverse reactions. Protective antibody titers (≥1:8) were observed in 96.9% of vaccinated cattle by 14–21 days post-vaccination (dpv), peaking at 60 dpv before declining at 150 dpv. The cell-mediated immune response peaked at 28 dpv. Clinical monitoring for one year showed that only 2% of vaccinated cattle developed mild LSD symptoms after nine months, with no mortality. At six months post-vaccination, seroconversion was 69.7%, with breed significantly influencing seropositivity. Conclusions: This study confirms the Goatpox vaccine’s safety and strong immunogenicity in cattle, marking its first large-scale evaluation in the Indian subcontinent. Further research is needed to assess long-term immunity and protection against virulent LSD strains. Full article

(This article belongs to the Section Epidemiology and Vaccination)

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15 pages, 1284 KiB

Open AccessArticle

Prevalence of Vaccine-Covered and Non-Covered HPV Genotypes Among Unvaccinated Women in Ankara: A Single-Center Study

by Ayfer Bakır and Mehmet Alican Sapmaz

Vaccines 2025, 13(6), 640; https://doi.org/10.3390/vaccines13060640 - 13 Jun 2025

Viewed by 385

Abstract

Background/Objectives: Understanding the regional distribution of human papillomavirus (HPV) genotypes is essential for guiding effective vaccination and screening strategies. This study aimed to assess the prevalence and distribution of HPV genotypes among unvaccinated women aged 30 years and older undergoing routine screening in [...] Read more.

Background/Objectives: Understanding the regional distribution of human papillomavirus (HPV) genotypes is essential for guiding effective vaccination and screening strategies. This study aimed to assess the prevalence and distribution of HPV genotypes among unvaccinated women aged 30 years and older undergoing routine screening in Ankara. It also aimed to compare the frequencies of genotypes included and not included in current vaccines and to investigate their association with cervical smear cytology. Methods: This descriptive, cross-sectional, single-center study was conducted at Ankara Etlik City Hospital between 15 November 2024 and 15 February 2025. A total of 500 sexually active, unvaccinated women aged 30 years or older were enrolled. Cervical swab samples were analyzed for HPV DNA and genotypes using real-time PCR (28-type panel), and cytology results were retrospectively obtained from medical records. Results: HPV infection was detected in 18.2% of participants. Among HPV-positive women, 71.4% had single-type and 28.6% had multiple-type infections. The most common high-risk genotypes among HPV-positive individuals were HPV 16 (13.2%), HPV 18 (13.2%), and HPV 59 (13.2%). While 35.2% of HPV-positive cases included genotypes covered by the nonavalent vaccine, 64.8% involved at least one genotype not covered, mainly HPV 59, 44, and 51. HPV was detected in 17% of individuals with normal cytology, 19% of those with atypical squamous cells of undetermined significance (ASC-US), and 100% of cases with low-grade squamous intraepithelial lesion (LSIL) (p < 0.001). Conclusions: The findings emphasize the persistence of high-risk and non-vaccine-covered HPV types in the population, highlighting the need for updated vaccination policies and the development of broader-spectrum vaccines aligned with local genotype profiles. Full article

(This article belongs to the Special Issue HPV Vaccination and Primary HPV Screening)

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13 pages, 1637 KiB

Open AccessArticle

Enhanced HIV-1 Neutralizing Antibody Breadth in HTLV-2 Co-Infected Individuals: Influence of Antiretroviral Regimen and B Cell Subset Distribution

by Eloisa Yuste, María J. Ruiz-De-León, José L. Casado, Ana Moreno, María J. Vivancos, María J. Pérez-Elías, Fernando Dronda, Carmen Quereda, Víctor Sánchez-Merino and Alejandro Vallejo

Vaccines 2025, 13(6), 639; https://doi.org/10.3390/vaccines13060639 - 13 Jun 2025

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Abstract

Background/Objectives: This study aimed to explore how HTLV-2 infection affects the production of broadly neutralizing antibodies (bNAbs) in persons with HIV-1 (PWH) and to assess the impact of boosted protease inhibitors (PIs). Methods: We evaluated broadly neutralizing antibody (bNAb) activity in 65 PWH, [...] Read more.

Background/Objectives: This study aimed to explore how HTLV-2 infection affects the production of broadly neutralizing antibodies (bNAbs) in persons with HIV-1 (PWH) and to assess the impact of boosted protease inhibitors (PIs). Methods: We evaluated broadly neutralizing antibody (bNAb) activity in 65 PWH, which included 27 who were also co-infected with HTLV-2. All participants were former injection drug users with HCV antibodies and were receiving suppressive antiretroviral therapy (ART). Neutralizing activity was assessed against six recombinant HIV-1 viruses that represent five different subtypes. B cell subsets were also analyzed. Results: HTLV-2 co-infection and the lack of ritonavir-boosted protease inhibitors (r-PIs) were both independently associated with higher neutralization scores (p = 0.017 and p = 0.005, respectively). Among those not on r-PIs, individuals co-infected with HTLV-2 showed significantly higher neutralization scores (p = 0.027) and a broader neutralization breadth (83.4% vs. 48.5%, p = 0.015) compared to those infected only with HIV-1. Additionally, HTLV-2 co-infected individuals had more resting memory B cells (p = 0.001) and fewer activated memory B cells (p = 0.017) than the HIV-1 mono-infected individuals. In our multivariate analysis, only HTLV-2 co-infection remained independently associated with neutralization scores (p = 0.027). Elite neutralizers (with a breadth score of ≥10) had more naive B cells and fewer resting memory B cells compared to those with weaker neutralization in both groups. Conclusions: Co-infection with HTLV-2 enhances bNAb production in PWH on suppressive ART and, in particular, in the absence of r-PI regimens. The prominent neutralizing activity corresponded with B cell subset distributions. The results suggest the complexity regarding the interaction between viral co-infections, antiretroviral regimens, and humoral immune compartments and may inform further H1V-1 pathogenesis inquiries or the appropriate design of a vaccine. Full article

(This article belongs to the Section HIV Vaccines)

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16 pages, 1535 KiB

Open AccessArticle

Strengthening Vaccine Regulation: Insights from COVID-19 Vaccines, Best Practices, and Lessons for Future Public Health Emergencies

by Razieh Ostad Ali Dehaghi, Alireza Khadem Broojerdi, Alaa Magdy, Marie Valentin, Juliati Dahlan, Obaidullah Malik, Richard H. Siggers, Edwin Nkansah and Hiiti B. Sillo

Vaccines 2025, 13(6), 638; https://doi.org/10.3390/vaccines13060638 - 12 Jun 2025

Viewed by 619

Abstract

Background: The COVID-19 pandemic necessitated immediate regulatory vaccine approvals to facilitate timely global access. The prevailing differences in economies and resources and the varying maturity of the regulatory systems worldwide resulted in different levels of capacity to ensure vaccine quality, safety, and [...] Read more.

Background: The COVID-19 pandemic necessitated immediate regulatory vaccine approvals to facilitate timely global access. The prevailing differences in economies and resources and the varying maturity of the regulatory systems worldwide resulted in different levels of capacity to ensure vaccine quality, safety, and efficacy. In addition to the Emergency Use Authorization or equivalent by some advanced regulatory agencies, the WHO issued Emergency Use Listings (EULs), among other tools, to streamline and expedite regulatory approvals globally. This study aimed to assess the regulatory strategies and best practices adopted during the COVID-19 vaccine approvals and gather lessons for future emergency preparedness. Methods: A mixed-method approach employing qualitative desk reviews and a cross-sectional study collected data from 194 national regulatory authorities (NRAs) across all WHO regions. Results: Three main approval processes were identified: procurement-driven, reliance-based, and independent evaluations. Wealthier countries with more mature regulatory systems were found to spend a longer time issuing approvals, primarily due to being the initial assessors of the vaccines’ quality, safety, and efficacy. Furthermore, various regulatory flexibilities and best practices centered around regulatory reliance, rolling reviews, fast-tracking reviews, and employing digital tools were identified. Notably, the WHO’s EULs were essential in facilitating the timely approval of vaccines globally, including in low- and middle-income countries. Conclusions: The findings suggest a significant turn in vaccine regulation theories and practice, emphasizing balancing speed with scientific validity. This necessitates the creation of thorough provisions for emergency preparedness, regulatory reliance, and administrative flexibility in regulatory practices worldwide. Full article

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

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14 pages, 1910 KiB

Open AccessSystematic Review

Safety and Immunogenicity of Co-Administration of Herpes Zoster Vaccines with Other Vaccines in Adults: A Systematic Review and Meta-Analysis

by Omid Rezahosseini, Aysan Bazargan, Mads Frederik Eiberg, Alexander Printzlau Korsgaard, Raziyeh Niyati, Christina Ekenberg, Lars Nørregaard Nielsen and Zitta Barrella Harboe

Vaccines 2025, 13(6), 637; https://doi.org/10.3390/vaccines13060637 - 12 Jun 2025

Cited by 1 | Viewed by 646

Abstract

Introduction: Herpes zoster (HZ), or shingles, is a vaccine-preventable disease with two approved vaccines: the live-attenuated vaccine (LZV) and the adjuvanted recombinant zoster vaccine (RZV). Evidence on the immunogenicity and adverse events (AEs) following co-administration with other vaccines in adults is limited. This [...] Read more.

Introduction: Herpes zoster (HZ), or shingles, is a vaccine-preventable disease with two approved vaccines: the live-attenuated vaccine (LZV) and the adjuvanted recombinant zoster vaccine (RZV). Evidence on the immunogenicity and adverse events (AEs) following co-administration with other vaccines in adults is limited. This systematic review and meta-analysis aims to evaluate the immunogenicity and safety of HZ vaccines when co-administered with other vaccines. Methods: We followed PRISMA 2020 guidelines and systematically searched multiple databases (January 1950 to February 2024) for studies on HZ vaccination with concomitant vaccines in adults (≥18 years). Observational studies, randomized controlled trials (RCTs), and non-randomized controlled trials were included, excluding reviews, case series, case reports, editorials, and non-English publications. Risk of bias was assessed using Cochrane tools (RoB 2 and ROBINS-I). A meta-analysis compared geometric mean concentration (GMC) ratios and vaccine response rates (VRRs) for RZV, applying the Hartung–Knapp adjustment. For LZV, meta-analysis was not feasible, and results were described narratively. AEs were analyzed using risk ratios and presented in forest plots. Results: Out of 369 search hits, ten RCTs were included. In six RCTs, RZV was co-administered with influenza, COVID-19, pneumococcal vaccines (PCV13, PPSV23), or Tdap. The pooled GMC mean difference was −0.04 (95% CI: −0.10 to 0.02, p = 0.19), and the pooled VRR was 1.00 (95% CI: 0.99 to 1.01, p = 0.59). Local and systemic AEs showed pooled relative risks of 0.99 (95% CI: 0.95 to 1.03, p = 0.73) and 1.01 (95% CI: 0.91 to 1.11, p = 0.90), respectively. LZV co-administration was investigated in four RCTs and was safe; however, co-administration with PPSV23 resulted in reduced immunogenicity. Conclusions: The co-administration of RZV with other vaccines was safe and immunogenic. However, limited evidence suggests that co-administration of LZV with PPSV23 reduced the immunogenicity of LZV through an unknown mechanism. Still, RZV co-administration could enhance vaccine uptake in vulnerable populations. Full article

(This article belongs to the Section Vaccine Advancement, Efficacy and Safety)

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12 pages, 704 KiB

Open AccessArticle

Challenges in Integrating Influenza Vaccination Among Older People in National Immunisation Program: A Population-Based, Cross-Sectional Study on Knowledge, Attitudes, Practices, and Acceptance of a Free Annual Program

by Mohd Shaiful Azlan Kassim, Rosnah Sutan, Noor Harzana Harrun, Faiz Daud, Noraliza Noordin Merican, Sheleaswani Inche Zainal Abidin, Ho Bee Kiau, Azniza Muhamad Radzi, Nagammai Thiagarajan, Norhaslinda Ishak, Tay Chai Li, Radziah Abdul Rashid, Sally Suriani Ahip, Nor Hazlin Talib, Saidatul Norbaya Buang, Noor Ani Ahmad, Zamberi Sekawi and Tan Maw Pin

Vaccines 2025, 13(6), 636; https://doi.org/10.3390/vaccines13060636 - 12 Jun 2025

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Abstract

Background: Influenza poses a significant threat to the health of Malaysians, particularly among the elderly population. It results in high levels of illness and mortality, becoming a financial burden on the government. Vaccination is widely recognised as the most effective measure for controlling [...] Read more.

Background: Influenza poses a significant threat to the health of Malaysians, particularly among the elderly population. It results in high levels of illness and mortality, becoming a financial burden on the government. Vaccination is widely recognised as the most effective measure for controlling the spread and impact of influenza. Objectives: This study sought to assess the knowledge, attitudes, and practices (KAP) regarding influenza and influenza vaccination among older adults attending primary healthcare centres in different states of Malaysia. Additionally, the study assessed the level of acceptance for a proposed free annual influenza vaccination program. Methods: A nationwide survey was conducted involving 672 older people aged 60 and above who visited nine primary healthcare centres in Malaysia. These centres were selected using proportionate to population size (PPS) sampling to ensure representation from each zone. Participants completed a validated self-reported questionnaire. Descriptive statistics were used to determine the levels of KAP, and a binomial logistic regression model was used to determine the predictors of acceptance for the proposed free annual vaccination program. Results: Most participants displayed a strong understanding of influenza illness (74.0%) and the vaccine (65.9%). Moreover, 76.4% of respondents exhibited a positive attitude towards influenza vaccination. However, the prevalence of good vaccination practices was relatively low, with only 29.2% of participants having a history of previous vaccination, and just 55.2% of these consistently practicing annual vaccination. The group acceptance rate for the proposed free annual influenza vaccination was 62.3%. Significant predictors of acceptance included a history of previous vaccination (good practice) (OR = 6.438, 95% CI = 1.16–35.71, p < 0.001), a positive attitude towards vaccines (OR = 21.98, 95% CI = 5.44–88.87, p = 0.033), and a good level of knowledge about the influenza vaccine (OR = 0.149, 95% CI = 0.03–0.79, p = 0.026). Conclusions: Increasing the uptake of influenza vaccination among the older population in Malaysia remains a significant challenge. It is recommended that a targeted, free annual influenza vaccination program be implemented for high-risk populations, particularly those with comorbidities and those who have shown greater receptiveness. In addition, health education strategies aimed at raising awareness and understanding of influenza should be prioritised. Strengthening epidemiological data collection and establishing systematic monitoring mechanisms are also essential to support these efforts. Full article

(This article belongs to the Special Issue Understanding Infectious Disease Vaccinations: Implications for Health and Safety)

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41 pages, 1829 KiB

Open AccessReview

Evolving SARS-CoV-2 Vaccines: From Current Solutions to Broad-Spectrum Protection

by Rui Qiao, Jiayan Li, Jiami Gong, Yuchen Shao, Jizhen Yu, Yumeng Chen, Yinying Lu, Luxuan Yang, Luanfeng Lin, Zixin Hu, Pengfei Wang, Xiaoyu Zhao and Wenhong Zhang

Vaccines 2025, 13(6), 635; https://doi.org/10.3390/vaccines13060635 - 12 Jun 2025

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Abstract

The continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the emergence of variants of concern (VOCs) underscore the critical role of vaccination in pandemic control. These mutations not only enhance viral infectivity but also facilitate immune evasion and diminish vaccine [...] Read more.

The continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the emergence of variants of concern (VOCs) underscore the critical role of vaccination in pandemic control. These mutations not only enhance viral infectivity but also facilitate immune evasion and diminish vaccine efficacy, necessitating ongoing surveillance and vaccine adaptation. Current SARS-CoV-2 vaccines, including inactivated, live-attenuated, viral vector, protein subunit, virus-like particle, and nucleic acid vaccines, face challenges due to the immune evasion strategies of emerging variants. Moreover, other sarbecoviruses, such as SARS-CoV-1 and SARS-related coronaviruses (SARSr-CoVs) pose a potential risk for future outbreaks. Thus, developing vaccines capable of countering emerging SARS-CoV-2 variants and providing broad protection against multiple sarbecoviruses is imperative. Several innovative vaccine platforms are being investigated to elicit broad-spectrum neutralizing antibody responses, offering protection against both current SARS-CoV-2 variants and other sarbecoviruses. This review presents an updated overview of the key target antigens and therapeutic strategies employed in current SARS-CoV-2 vaccines. Additionally, we summarize ongoing approaches for the development of vaccines targeting infectious sarbecoviruses. Full article

(This article belongs to the Special Issue Vaccination-Induced Antibody and B Cell Immune Response)

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17 pages, 1771 KiB

Open AccessArticle

Impact of the National Vaccination Strategy on the Prevalence of Streptococcus pneumoniae and Its Serotypes Among Clinically Healthy Children Under Six Years of Age During and After the COVID-19 Pandemic

by Ivelina Trifonova, Victoria Levterova, Ivan Simeonovski, Magi Ivanova, Nadia Brankova and Todor Kantardzhiev

Vaccines 2025, 13(6), 634; https://doi.org/10.3390/vaccines13060634 - 12 Jun 2025

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Abstract

Introduction: An effective vaccination strategy requires monitoring serotype changes by geography and age. This study analyzed Streptococcus pneumoniae serotypes in healthy children under 6 years of age vaccinated with PCV10 in Bulgaria from October 2021 to May 2025. Methods: A total of 569 [...] Read more.

Introduction: An effective vaccination strategy requires monitoring serotype changes by geography and age. This study analyzed Streptococcus pneumoniae serotypes in healthy children under 6 years of age vaccinated with PCV10 in Bulgaria from October 2021 to May 2025. Methods: A total of 569 children were screened for the lytA and cpsA genes viareal-time polymerase chain reaction (real-time PCR). Positive samples were typed using relevant kits, and 76 serotypes/serogroups of S. pneumoniae were identified. Results: Nasopharyngeal swabs from 232 children (40.8%) were found to carry S. pneumoniae, and a total of 255 serotypes were detected, with 19B/19C (17.2%), 6C (10.7%), and 15B/15C (9.8%) being the most prevalent. Of these, 91 serotypes (15.9%) were included in at least one vaccine, while the remaining 164 serotypes (25.4%) were not. The carriage rate reduced to 22% in 2023 but increased to 47% in 2024. Overall, younger children had lower carriage rates (p < 0.05), with serotype 6C being more common in children under 12 months of age (25%). Approximately 9.1% of pneumococcal carriage cases involved co-detected serotypes, with significantly higher co-detection rates for 19B/19C, 15B/15C, 10B, 10F/C, 23B, 7C/40, 23A, and 24A compared with mono-detection rates (p < 0.05). Conclusions: 19B/19C, 6C, 15B/15C, and 19A were identified as the main serotypes. Children over 3 years of age were also more likely to carry multiple pneumococci. These findings emphasize the need to reassess childhood vaccination strategies to curb the spread of antibiotic-resistant serotypes. Full article

(This article belongs to the Section Epidemiology and Vaccination)

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20 pages, 1738 KiB

Open AccessArticle

Universal Bacterium-Vectored COVID-19 Vaccine Expressing Early SARS-CoV-2 Conserved Proteins Cross-Protects Against Late Variants in Hamsters

by Qingmei Jia, Helle Bielefeldt-Ohmann, Saša Masleša-Galić, Richard A. Bowen and Marcus A. Horwitz

Vaccines 2025, 13(6), 633; https://doi.org/10.3390/vaccines13060633 - 12 Jun 2025

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Abstract

Background/Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus Disease 2019 (COVID-19), has rapidly evolved, giving rise to multiple Variants of Concern—including Alpha, Beta, Gamma, Delta, and Omicron—which emerged independently across different regions. Licensed COVID-19 vaccines primarily target the [...] Read more.

Background/Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus Disease 2019 (COVID-19), has rapidly evolved, giving rise to multiple Variants of Concern—including Alpha, Beta, Gamma, Delta, and Omicron—which emerged independently across different regions. Licensed COVID-19 vaccines primarily target the highly mutable spike protein, resulting in reduced efficacy due to immune escape by emerging variants. Previously, we developed a live attenuated Francisella tularensis LVS ΔcapB single-vector platform COVID-19 vaccine, rLVS ΔcapB/MN, expressing the conserved membrane (M) and nucleocapsid (N) proteins from the early SARS-CoV-2 WA-01/2020 strain. In this study, we evaluate the efficacy of rLVS ΔcapB/MN and an enhanced version, rLVS ΔcapB::RdRp/MN, which additionally expresses the conserved RNA-dependent RNA polymerase (RdRp) protein from the same strain, in a hamster model. Methods: Both vaccine candidates were administered orally or intranasally to golden Syrian hamsters (equal numbers of males and females) and evaluated against intranasal challenge with SARS-CoV-2 Delta (B.1.617.2-AY.1) and Omicron (BA.5) variants. Results: Vaccinated animals developed robust, TH1-biased IgG responses specific to the nucleocapsid protein. Following SARS-CoV-2 challenge, immunized hamsters exhibited reduced weight loss, lower oropharyngeal and lung viral titers, and improved lung pathology scores compared with unvaccinated controls. Conclusion: These findings support the potential of this universal vaccine to provide broad protection against current and future SARS-CoV-2 variants, with minimal need for updating. Full article

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

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29 pages, 8225 KiB

Open AccessArticle

Evaluation of Peptide-Based Vaccines Against Group A Streptococcus in Staphylococcus aureus-Infected Mice

by Ahmed O. Shalash, Haolan Sun, Yiru Cui, Jingwen Wang, Barb Arnts, Jannah Bauer, Waleed M. Hussein, Zeinab G. Khalil, Mariusz Skwarczynski and Istvan Toth

Vaccines 2025, 13(6), 632; https://doi.org/10.3390/vaccines13060632 - 12 Jun 2025

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Abstract

Background: Group A Streptococcus (GAS) is a major human pathogen associated with serious diseases. Evaluating immune responses against GAS vaccines—immunogenicity, quality, and efficacy—is complicated by interference from co-infections, like Staphylococcus aureus (S. aureus). We aimed to evaluate peptide-based GAS vaccines in [...] Read more.

Background: Group A Streptococcus (GAS) is a major human pathogen associated with serious diseases. Evaluating immune responses against GAS vaccines—immunogenicity, quality, and efficacy—is complicated by interference from co-infections, like Staphylococcus aureus (S. aureus). We aimed to evaluate peptide-based GAS vaccines in mice for antisera efficacy against standard and mutant GAS strains and to assess immunological methods under co-infection conditions. Methods: Female C57BL/6 mice were infected with S. aureus and immunized with various M-protein-derived peptide antigens: J8, J8i, J8i-J8i, and the native p145 sequence. Two novel, conserved M-protein-derived antigens (NTD and CTD2) were also evaluated. Enzyme-linked immunosorbent assays (ELISAs) were used to assess immunogenicity and GAS-specific antibody responses. Peptide antigens were either conjugated to or physically mixed with the PADRE T-helper epitope and tested for enhanced antisera immunogenicity and opsonic efficacy. Result: ELISA against the immunizing peptides as coating antigens reflected the immunogenicity, while p145-based ELISA correlated with GAS-specific antibody titres without S. aureus interference for J8-based vaccines. Immunogenicity ranked J8 > J8i ≈ J8i-J8i > p145. NTD and CTD2 antisera demonstrated opsonic activity, indicating protective potential. PADRE–J8 conjugates significantly enhanced antibody magnitude and quality, producing strong opsonic bactericidal responses against both standard and p145-mutant GAS strains. PADRE–J8i was effective only against standard strains. This is the first report to suggest at least two B-cell epitopes within the J8i peptide. Conclusion: These findings support the diagnostic utility of p145, NTD, and CTD2 under co-infection settings, and the vaccine potential of J8, NTD, and CTD2, particularly when conjugated to a T helper for enhanced antigen presentation. Full article

(This article belongs to the Collection Advance in Nanoparticles as Vaccine Adjuvants)

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Vaccines, Volume 13, Issue 6 (June 2025) – 114 articles

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