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Vaccines, Volume 13, Issue 6 (June 2025) – 100 articles

Cover Story (view full-size image): Chlamydia abortus is a major bacterial pathogen of sheep worldwide, causing the death of lambs in utero. Current live vaccines have safety issues, causing disease in some animals. A new, safer and efficacious vaccine has been developed that cannot cause disease, and reduces the shedding of the pathogen in vaginal excretions following parturition, thus limiting potential transmission to other animals. The vaccine is based on a preparation of the outer membrane of the bacteria and has been optimised to determine an appropriate dose that can be delivered in a single inoculation to sheep. In the study reported here, the vaccine has been optimised further by comparing the effects of different adjuvants on its protective efficacy in order to identify the best adjuvant to include in the final formulation for commercialisation. View this paper
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13 pages, 526 KiB  
Article
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
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)
7 pages, 158 KiB  
Commentary
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
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
17 pages, 2285 KiB  
Article
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
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 (108.3 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 106.0 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  
Article
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
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  
Systematic 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
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 Efficacy and Safety)
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13 pages, 499 KiB  
Article
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
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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 Human Vaccines and Public Health)
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14 pages, 2294 KiB  
Article
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
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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)
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15 pages, 1284 KiB  
Article
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 54
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  
Article
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
Viewed by 129
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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17 pages, 1535 KiB  
Article
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 175
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  
Systematic 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
Viewed by 180
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 Efficacy and Safety)
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12 pages, 704 KiB  
Article
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
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41 pages, 1829 KiB  
Review
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
Viewed by 233
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  
Article
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
Viewed by 140
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)
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20 pages, 1738 KiB  
Article
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
Viewed by 168
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  
Article
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
Viewed by 146
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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22 pages, 1335 KiB  
Article
Evaluation of Immunogenicity of an Orf Virus Vector-Based Vaccine Delivery Platform in Sheep
by Sean R. Wattegedera, Jackie Thomson, Lesley Coulter, Ann Wood, Rebecca K. McLean, Holly Hill, Cameron Cunnea, Karen Snedden, Ann Percival, Javier Palarea-Albaladejo, Gary Entrican, David Longbottom, David J. Griffiths and Colin J. McInnes
Vaccines 2025, 13(6), 631; https://doi.org/10.3390/vaccines13060631 - 11 Jun 2025
Viewed by 158
Abstract
Background/Objective: Virus-based vaccine vectors have been widely utilised in commercial vaccines, predominantly for virus infections. They also offer promise for bacterial diseases, for which many vaccines are sub-optimal or ineffective. It is well-established for chlamydial infections, including ovine enzootic abortion, that the major [...] Read more.
Background/Objective: Virus-based vaccine vectors have been widely utilised in commercial vaccines, predominantly for virus infections. They also offer promise for bacterial diseases, for which many vaccines are sub-optimal or ineffective. It is well-established for chlamydial infections, including ovine enzootic abortion, that the major outer membrane protein (MOMP) antigen is protective. Immune responses strongly associated with controlling Chlamydiae include cellular interferon-gamma (IFN-γ) production. Methods: A study was conducted to compare the ability of a modified Orf virus vector directly with a modified sheep maedi visna virus vector to deliver the C. abortus antigen ompA and stimulate vaccine-induced responses in sheep. The Orf virus-based vaccine (mORFV-ompA) was found to be more effective in stimulating MOMP-specific antibodies and cellular antigen-driven IFN-γ in immunised sheep. This mORFV-ompA vaccine was assessed in a follow-up immunogenicity investigation in sheep, where the cellular and humoral immune responses elicited following immunisation with the live or inactivated vaccine were determined. Sheep were immunised intramuscularly with a live mORFV-ompA (n = 10) or an inactivated mORFV-ompA (n = 10). An additional group of 10 sheep served as unvaccinated controls. Results: Serological anti-MOMP antibodies and cellular recall responses of peripheral blood mononuclear cells to the native C. abortus antigen were assessed. Immunisation with either the live or inactivated mORFV-ompA-induced anti-MOMP immunoglobulin-G. Antigen-specific cellular responses, characterised by the secretion of IFN-γ and interleukin (IL)-17A, with negligible IL-10 and no IL-4, were detected in lymphocyte stimulation assays from both mORFV groups. No antibody responses to the mORFV platform were detected following immunisations. Conclusions: Both live and inactivated vaccines have the potential to be a platform technology for deployment in sheep. This addresses a notable gap in veterinary vaccine development where the induction of both humoral responses and cellular responses is required without using an adjuvant. The successful use of the MOMP candidate antigen suggests potential utility for bacterial disease deployment. Full article
(This article belongs to the Section Veterinary Vaccines)
18 pages, 2527 KiB  
Article
Targeting Azole-Resistant Candida albicans: Tetrapeptide Tuftsin-Modified Liposomal Vaccine Induces Superior Immune Protection
by Masood A. Khan, Arif Khan, Abdullah M. Alnuqaydan, Aqel Albutti, Basmah F. Alharbi and Mohammad Owais
Vaccines 2025, 13(6), 630; https://doi.org/10.3390/vaccines13060630 - 11 Jun 2025
Viewed by 191
Abstract
Background/objectives: Candida albicans is a major fungal pathogen that poses a serious threat to immunocompromised individuals. The increasing prevalence of fluconazole-resistant strains presents a critical clinical challenge, emphasizing the urgent need for novel therapeutic strategies. This study aimed to evaluate the prophylactic potential [...] Read more.
Background/objectives: Candida albicans is a major fungal pathogen that poses a serious threat to immunocompromised individuals. The increasing prevalence of fluconazole-resistant strains presents a critical clinical challenge, emphasizing the urgent need for novel therapeutic strategies. This study aimed to evaluate the prophylactic potential of a new liposomal vaccine formulation, Tuft-lip-WCAgs, comprising Tuftsin and C. albicans whole cell antigens, in providing immune protection against systemic candidiasis. Methods: The vaccine formulation was tested in a murine model of systemic C. albicans infection. The efficacy of the Tuft-lip-WCAg vaccine was evaluated through a survival analysis, fungal burden assessments, and immunological profiling. Immune responses were assessed by measuring serum antibody titers and isotypes, T cell proliferation, and cytokine secretion (IFN-γ and IL-4) from splenocytes. Results: FLZ treatment showed weak antifungal activity, high MIC values, and limited biofilm disruption and failed to ensure long-term survival, resulting in 100% mortality by day 40. In contrast, Tuft-lip-WCAg vaccination was well tolerated and conferred complete protection, with no detectable fungal burden by day 40. Vaccinated mice exhibited significantly elevated total antibody titers (166,667 ± 14,434), increased IgG2a levels, and enhanced T cell proliferation (stimulation index: 3.9 ± 0.84). Splenocytes from immunized mice secreted markedly higher levels of IFN-γ (634 ± 128 pg/mL) and IL-4 (582 ± 82 pg/mL), indicating a balanced Th1/Th2 immune response. Tuft-lip-WCAg vaccination also achieved 100% survival and the lowest kidney fungal burden (556 ± 197 CFUs/g). Conclusions: Tuft-lip-WCAg formulation is a safe, immunogenic, and highly effective vaccine candidate that offers complete protection against drug-resistant C. albicans in a murine model. These findings support its promise as a novel immunoprophylactic strategy, particularly for immunocompromised populations at high risk of invasive candidiasis. Full article
(This article belongs to the Special Issue Peptide-Based Vaccines)
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19 pages, 1427 KiB  
Article
Citrullinated ENO1 Vaccine Enhances PD-1 Blockade in Mice Implanted with Murine Triple-Negative Breast Cancer Cells
by Ricardo A. León-Letelier, Alejandro M. Sevillano-Mantas, Yihui Chen, Soyoung Park, Jody Vykoukal, Johannes F. Fahrmann, Edwin J. Ostrin, Candace Garrett, Rongzhang Dou, Yining Cai, Fu-Chung Hsiao, Jennifer B. Dennison, Eduardo Vilar, Banu K. Arun, Samir Hanash and Hiroyuki Katayama
Vaccines 2025, 13(6), 629; https://doi.org/10.3390/vaccines13060629 - 11 Jun 2025
Viewed by 226
Abstract
Background/Objectives:Cancer vaccine targets mostly include mutations and overexpressed proteins. However, cancer-associated post-translational modifications (PTMs) may also induce immune responses. Previously, our group established the enzyme protein arginine deiminase type-2 (PADI2), which catalyzes citrullination modification, is highly expressed in triple-negative breast cancer (TNBC), [...] Read more.
Background/Objectives:Cancer vaccine targets mostly include mutations and overexpressed proteins. However, cancer-associated post-translational modifications (PTMs) may also induce immune responses. Previously, our group established the enzyme protein arginine deiminase type-2 (PADI2), which catalyzes citrullination modification, is highly expressed in triple-negative breast cancer (TNBC), promoting antigenicity. Methods: Here, we show the workflow of designing citrullinated enolase 1 (citENO1) vaccine peptides identified from breast cancer cells by mass spectrometry and demonstrate TNBC vaccine efficacy in the mouse model. Immunized mice with citENO1 peptides or the corresponding unmodified peptides, plus Poly I:C as an adjuvant, were orthotopically implanted with a TNBC murine cell line. Results: Vaccination with citENO1, but not unmodified ENO1 (umENO1), induced a greater percentage of activated CD8+ PD-1+ T cells and effector memory T cells in skin-draining lymph nodes (SDLNs). Remarkably, the citENO1 vaccine delayed tumor growth and prolonged overall survival, which was further enhanced by PD-1 blockade. Conclusions: Our data suggest that cancer-restricted post-translational modifications provide a source of vaccines that induce an anti-cancer immune response. Full article
(This article belongs to the Special Issue Personalised Cancer Vaccines)
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20 pages, 2626 KiB  
Article
Development of an Influenza/COVID-19 Combination mRNA Vaccine Containing a Novel Multivalent Antigen Design That Enhances Immunogenicity of Influenza Virus B Hemagglutinins
by Elena Thornhill-Wadolowski, Dana L. Ruter, Feng Yan, Mayur Gajera, Evan Kurt, Labannya Samanta, Kimberlin Leigh, Jianbo Zhu, Zhijun Guo, Zihao Wang, Yuanqing Liu, Jaewoo Lee and Marcin Bugno
Vaccines 2025, 13(6), 628; https://doi.org/10.3390/vaccines13060628 - 11 Jun 2025
Viewed by 312
Abstract
Background/Objectives: Developing next-generation mRNA-based seasonal influenza vaccines remains challenging, primarily because of the relatively low immunogenicity of influenza B hemagglutinin (HA) antigens. We describe a systematic vaccine development strategy that combined vector and antigen design optimization. Methods: Novel untranslated region (UTR) sequences and [...] Read more.
Background/Objectives: Developing next-generation mRNA-based seasonal influenza vaccines remains challenging, primarily because of the relatively low immunogenicity of influenza B hemagglutinin (HA) antigens. We describe a systematic vaccine development strategy that combined vector and antigen design optimization. Methods: Novel untranslated region (UTR) sequences and a hybrid poly(A) tail were used to increase plasmid stability and mRNA expression. Fusion proteins containing HA antigens linked by T4 foldon domains were engineered to enhance the immune responses against influenza B HA antigens and to permit the expression of multiple HA ectodomains from a single mRNA species. The vaccine performance was verified in a traditional encapsulated lipid nanoparticle (LNP) formulation that requires long-term storage at temperatures below −15 °C as well as in a proprietary thermo-stable LNP formulation developed for the long-term storage of the mRNA vaccine at 2–8 °C. Results: In preclinical studies, our next-generation seasonal influenza vaccine tested alone or as a combination influenza/COVID-19 mRNA vaccine elicited hemagglutination inhibition (HAI) titers significantly higher than Fluzone HD, a commercial inactivated influenza vaccine, across all 2024/2025 seasonal influenza strains, including the B/Victoria lineage strain. At the same time, the combination mRNA vaccine demonstrated superior neutralizing antibody titers to 2023/2024 Spikevax, a commercial COVID-19 comparator mRNA vaccine. Conclusions: Our data demonstrate that the multimerization of antigens expressed as complex fusion proteins is a powerful antigen design approach that may be broadly applied toward mRNA vaccine development. Full article
(This article belongs to the Section DNA and mRNA Vaccines)
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19 pages, 1915 KiB  
Review
Predicting the Epidemiological Effects in the United Kingdom of Moving from PCV13 to PCV15 in the Routine Pediatric 1 + 1 Vaccination Schedule
by Rachel J. Oidtman, Natalie Banniettis, Jessica Weaver, Ian R. Matthews, Dionysios Ntais, Giulio Meleleo, Tufail M. Malik, John C. Lang and Oluwaseun Sharomi
Vaccines 2025, 13(6), 627; https://doi.org/10.3390/vaccines13060627 - 10 Jun 2025
Viewed by 264
Abstract
Background/Objectives: Pneumococcal conjugate vaccines (PCVs) were first introduced in the pediatric UK National Immunization Programme (NIP) in 2006 and subsequently led to a significant decline in invasive pneumococcal disease (IPD). In 2020, the UK NIP reduced the pediatric PCV dosing schedule from two [...] Read more.
Background/Objectives: Pneumococcal conjugate vaccines (PCVs) were first introduced in the pediatric UK National Immunization Programme (NIP) in 2006 and subsequently led to a significant decline in invasive pneumococcal disease (IPD). In 2020, the UK NIP reduced the pediatric PCV dosing schedule from two infant doses and one toddler dose (2 + 1) to one infant dose and one toddler dose (1 + 1). This analysis evaluated the public health impact of pediatric vaccination with PCV15 versus PCV13 under a 1 + 1 schedule. Methods: A population-level compartmental model was previously adapted to the UK setting. The impact on the IPD incidence of vaccination with PCV15 versus PCV13 under a 1 + 1 schedule was evaluated over a 20-year time horizon. The uncertainty regarding the vaccine efficacy (VE) of PCV13 and PCV15 under a 1 + 1 schedule was investigated through a probabilistic sensitivity analysis, i.e., the PCV VE under a 1 + 1 schedule was assumed to be 0–24% lower than the PCV VE under a 2 + 1 schedule. Results: Relative to the initial IPD incidence, vaccination with PCV13 and PCV15 under a 1 + 1 schedule resulted in the IPD incidence in children <2 years old increasing by 11.1% (95% region: 8.4–14.5%) and 3.5% (0.2–7.7%), respectively, over the time horizon. At the end of the time horizon, in the overall population, PCV15 would lead to a 6.0% lower IPD incidence than PCV13 (10.70 IPD cases per 100,000 versus 11.38 per 100,000, respectively). Conclusions: Switching from PCV13 to PCV15 for routine pediatric vaccinations under the 1 + 1 dosing schedule in the UK led to a lower IPD incidence in both the pediatric and overall populations. Full article
(This article belongs to the Special Issue Pneumococcal Vaccines: Current Status and Future Prospects)
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22 pages, 3342 KiB  
Article
A High-Throughput and Robust Relative Potency Assay Measuring Human Cytomegalovirus Infection in Epithelial Cells for Vaccine Development
by Nicole M. Smiddy, Nisarg Patel, Matthew C. Troutman, Kristine M. Kearns, Zachary P. Davis, Christopher S. Adams, Carl Hofmann, Donald J. Warakomski, Harrison Davis, Daniel Spatafore, Adam Kristopeit, Pete DePhillips and John W. Loughney
Vaccines 2025, 13(6), 626; https://doi.org/10.3390/vaccines13060626 - 10 Jun 2025
Viewed by 511
Abstract
Background/Objectives: A preventative vaccine against human cytomegalovirus (HCMV) infection and disease remains an unmet medical need. Several attenuated virus and antigen-based HCMV vaccine candidates have been proposed; however, development challenges have limited their progression through the clinical pipeline. Method: A high-throughput and robust [...] Read more.
Background/Objectives: A preventative vaccine against human cytomegalovirus (HCMV) infection and disease remains an unmet medical need. Several attenuated virus and antigen-based HCMV vaccine candidates have been proposed; however, development challenges have limited their progression through the clinical pipeline. Method: A high-throughput and robust relative potency assay, Imaging of Relative Viral Expression (IRVE), was developed and applied to measure the infection of a live-attenuated HCMV vaccine candidate in ARPE-19 epithelial cells. The IRVE assay measures HCMV infection by immunostaining Immediate Early 1 (IE1) protein and enumeration of IE1-positive, infected cells against total cells. Increased throughput was accomplished using 384-well plate automation on a custom-designed integrated robotic system. Results: The IRVE assay effectively measures relative potency changes in an HCMV vaccine candidate under different upstream processes, downstream processes, and formulation conditions. Key assay parameters including microplate format, cell density, serum concentration, infection time and influence of cell age were evaluated and optimized. The IRVE assay was correlated to historical, lower throughput HCMV potency assays, including plaque and Infectivity of Early Gene Expression (IEE), validating its application as a potency screening tool. Conclusions: The IRVE assay has been successfully implemented to support HCMV vaccine development over several years of clinical development. Full article
(This article belongs to the Special Issue Innovations in Vaccine Technology)
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23 pages, 4903 KiB  
Article
Highly Effective mRNA-LNP Vaccine Against Respiratory Syncytial Virus (RSV) in Multiple Models
by Huarong Bai, Xueliang Yu, Yue Gao, Qin Li, Baigang Wen and Rongkuan Hu
Vaccines 2025, 13(6), 625; https://doi.org/10.3390/vaccines13060625 - 10 Jun 2025
Viewed by 384
Abstract
Background: The transmembrane fusion (F) protein of RSV plays important roles in RSV pathogenesis as it mediates the fusion between the virus and the target cell membrane. During the fusion process, the F protein transits from a metastable state (prefusion, preF) to a [...] Read more.
Background: The transmembrane fusion (F) protein of RSV plays important roles in RSV pathogenesis as it mediates the fusion between the virus and the target cell membrane. During the fusion process, the F protein transits from a metastable state (prefusion, preF) to a stable state (postfusion, postF) after the merging of the virus and cell membranes. The majority of highly neutralizing antibodies induced by natural infection or immunization target the preF form, which makes it the preferred antigen for vaccine development. Methods: Here, we designed an effective RSV mRNA vaccine, STR-V003, consisting of mRNA encoding preF protein in lipid nanoparticles (LNPs). The immunogenicity, protection efficacy and toxicity were measured in multiple animal models. Results: STR-V003 demonstrated robust immunogenicity in both mice and cotton rats, inducing high levels of neutralizing antibodies and RSV preF-specific IgG antibodies and significantly reducing the RSV viral loads in the lung and nose tissue of challenged animals. In addition, STR-V003 did not show significant enhancement of lung pathology without causing vaccine-enhanced disease (VED). The repeated dose general toxicology studies and local tolerance studies of STR-V003 were evaluated in rats and non-human primate (NHP). Conclusions: STR-V003 demonstrates a favorable safety profile and induces robust protective immunity against RSV. Full article
(This article belongs to the Special Issue The Development of mRNA Vaccines)
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28 pages, 543 KiB  
Systematic Review
Mapping Behavioral and Social Drivers of Influenza Vaccine Uptake in Older Adults: A Scoping Review
by Enming Zhang, Shuhui Shang, Yufei Xing, Jiasong Cui, Chen Pan, Holly Seale and Qiong Fang
Vaccines 2025, 13(6), 624; https://doi.org/10.3390/vaccines13060624 - 10 Jun 2025
Viewed by 323
Abstract
Background/Objectives: Influenza vaccination plays a crucial role in reducing morbidity and mortality among older adults; however, uptake remains suboptimal, particularly in the post-COVID-19 pandemic. In many settings, countries have not recovered their influenza vaccine coverage rates to the same level as pre-COVID. Therefore, [...] Read more.
Background/Objectives: Influenza vaccination plays a crucial role in reducing morbidity and mortality among older adults; however, uptake remains suboptimal, particularly in the post-COVID-19 pandemic. In many settings, countries have not recovered their influenza vaccine coverage rates to the same level as pre-COVID. Therefore, this scoping review systematically identified the behavioral and social drivers (BeSD) influencing influenza vaccination among older adults using the BeSD framework. Methods: A systematic search across five databases included quantitative, qualitative, and mixed-methods studies involving individuals aged 60 years and older. Data were charted across four BeSD domains: thinking and feeling, social processes, motivation, and practical issues. Results: Thirty-nine studies from 24 countries were included. Key barriers encompassed safety concerns, misinformation, financial burdens, logistical challenges, and cultural and language barriers. While motivation was positively associated with vaccination intentions, the transition from intention to behavior remains underexplored, and practical issues have received comparatively limited research attention. Conclusions: These findings underscore the need for multifaceted, behaviorally informed interventions and greater inclusion of under-resourced settings to support equitable influenza vaccination strategies for healthy aging. Full article
(This article belongs to the Special Issue Vaccination in a Post-Pandemic World)
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12 pages, 426 KiB  
Article
Post-Marketing Surveillance of Nirsevimab: Safety Profile and Adverse Event Analysis from Spain’s 2023–2024 RSV Immunisation Campaign
by Pablo Estrella-Porter, Elisa Correcher-Martínez, Alejandro Orrico-Sánchez and Juan José Carreras
Vaccines 2025, 13(6), 623; https://doi.org/10.3390/vaccines13060623 - 10 Jun 2025
Viewed by 433
Abstract
Background: Respiratory syncytial virus (RSV) poses a significant health burden in children, being the major cause of lower respiratory tract infection (LRTI), including bronchiolitis. During the 2023–2024 RSV season, Spain introduced nirsevimab, a monoclonal antibody for universal RSV prophylaxis in infants. This study [...] Read more.
Background: Respiratory syncytial virus (RSV) poses a significant health burden in children, being the major cause of lower respiratory tract infection (LRTI), including bronchiolitis. During the 2023–2024 RSV season, Spain introduced nirsevimab, a monoclonal antibody for universal RSV prophylaxis in infants. This study reviews the safety of nirsevimab through post-marketing surveillance. Material and Methods: A descriptive pharmacovigilance study was made based on spontaneous reporting data of suspected adverse events (SAEs) from the Spanish Pharmacovigilance System for Medicinal Products for Human Use (SEFV-H) and industry reports. SAEs reported between September 2023 and May 2024 were extracted from the Spanish Pharmacovigilance Adverse Reactions Data (FEDRA) database. Cases were analysed by sex, age, severity, and SAEs classification using the Preferred Terms (PT) level of the Medical Dictionary for Regulatory Activities (MedDRA). Reporting rates were estimated based on immunization coverage and birth data. Results: Sixty-seven cases reported 141 SAEs, yielding an overall rate of 23.1 cases per 100,000 doses. Common events included rash (8.51%), drug ineffectiveness (7.09%), and pyrexia (7.09%). Serious events constituted 53.70% of reports, including two fatalities (3.00%). No new safety signals or unexpected risks, such as antibody-dependent enhancement (ADE), were identified. Discussion: SAEs reported peaked early in the campaign, reflecting heightened reporting in new immunization programs. The safety profile aligns with clinical trial findings and regulatory expectations, confirming nirsevimab’s benefit–risk balance. Continued pharmacovigilance is critical for maintaining public trust in RSV prophylaxis. Nirsevimab demonstrated a favorable safety profile during Spain’s initial universal RSV immunization campaign in infants, supporting its continued use in reducing RSV-related morbidity. Full article
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17 pages, 636 KiB  
Article
A Multi-Center Study on Sensitization to Thimerosal in North-Eastern Italy, 1997–2023: Prevalence, Risk Factors, the Role of Occupation and the Impact of Vaccinations
by Luca Cegolon, Emilia Patriarca and Francesca Larese Filon
Vaccines 2025, 13(6), 622; https://doi.org/10.3390/vaccines13060622 - 9 Jun 2025
Viewed by 394
Abstract
Background: Thimerosal has been widely used as a preservative to prevent microbial growth in medications and vaccines. However, in 1999 its removal from vaccine formulations was called for due to concerns about its potential side effects on humans, with subsequent reduced sensitizations [...] Read more.
Background: Thimerosal has been widely used as a preservative to prevent microbial growth in medications and vaccines. However, in 1999 its removal from vaccine formulations was called for due to concerns about its potential side effects on humans, with subsequent reduced sensitizations at patch tests. The present multi-center study investigated the epidemiological, occupational and temporal pattern of sensitization to Thimerosal in North-Eastern Italy during 1997–2023 and associated factors. Methods: Due to variability in patch testing and positive reactions by the centers, this study was broken down by three periods: 1997–2004 (including all centers but Trieste); 1997–2015 (considering only Padua and Pordenone); and 2010–2023 (considering only Trieste and Pordenone). Multiple logistic regression was used to investigate prevalence of sensitization to Thimerosal and associated factors. Results were expressed as adjusted odds ratio (aOR) with 95% confidence intervals (95%CI). Results: Prevalence of positive patch test reactions to Thimerosal decreased from (8.13%) in 1997 to 0.95% in 2023 across all centers combined. Prevalence of positivity to Thimerosal was 9.49% during 1997–2004 (in all centers yet excluding Trieste), 8.41% during 1997–2015 (considering only Padua and Pordenone) and 4.01% during 2010–2023 (considering only Trieste and Pordenone). A significantly decreasing trend of Thimerosal sensitization was observed during 1997–2015 (aOR = 0.94; 95%CI: 0.92; 0.95). Regardless of the study period, sensitization to Thimerosal was consistently and significantly higher among health care workers (HCWs) and in patients born during 1981–1990. Conclusions: The significantly decreasing prevalence of sensitization to Thimerosal over time likely reflected removal policies from vaccines and medications after 1999. Likewise, the higher prevalence of patch test reactions in patients born during 1981–1990 may mirror the widespread presence of this hapten in vaccines and medications in the 1980ies. Moreover, the increased prevalence of patch test reactions positive to Thimerosal in HCWs probably reflected higher influenza vaccination uptake in this group compared to other occupational categories. Positive patch test reactions to Thimerosal after 2000 were likely clinically irrelevant though. Full article
(This article belongs to the Section Epidemiology)
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26 pages, 395 KiB  
Review
Vaccination Strategies and Research Gaps in Hepatitis E Virus for Special Populations
by Meng Wang, Binwei Duan, Mengcheng Liu, Yuxuan Zhang, Feng Wu, Guangming Li and Yabo Ouyang
Vaccines 2025, 13(6), 621; https://doi.org/10.3390/vaccines13060621 - 9 Jun 2025
Viewed by 392
Abstract
Background: Hepatitis E virus (HEV) infection poses a significant health risk across diverse demographic groups, particularly among pregnant women, immunocompromised individuals, patients with chronic liver disease, and the elderly. The global epidemiology of HEV reveals distinct patterns of prevalence, transmission, and disease severity [...] Read more.
Background: Hepatitis E virus (HEV) infection poses a significant health risk across diverse demographic groups, particularly among pregnant women, immunocompromised individuals, patients with chronic liver disease, and the elderly. The global epidemiology of HEV reveals distinct patterns of prevalence, transmission, and disease severity among these populations, necessitating targeted vaccination strategies. The licensing of the Hecolin (HEV 239) vaccine offers promise, but gaps in clinical trial data and varying immune responses in high-risk groups challenge its widespread applicability. Scope: This review synthesizes data on HEV’s epidemiology, discusses the susceptibility of vulnerable populations, evaluates the efficacy and safety of HEV 239, and highlights the urgent need for clinical research tailored to these groups. Key findings underscore the complexity of vaccine response influenced by immunological, physiological, and environmental factors. Additionally, potential advancements in vaccine technology, including the development of broad-spectrum vaccines and innovative delivery systems, are discussed as future directions. Strategies: Addressing regulatory, economic, and logistical barriers remains crucial for effective HEV vaccination programs. A multidisciplinary approach integrating public health policy, rigorous clinical evaluations, and collaborative frameworks is essential to ensure equitable access to HEV vaccination, ultimately improving health outcomes on a global scale. Full article
(This article belongs to the Special Issue Hepatitis Vaccines: Safety, Efficacy and Global Impact)
21 pages, 2197 KiB  
Article
Production and Immune Response Against Pandemic Influenza Candidate Vaccines as Preparedness Against the Circulating H5N1 Influenza Viruses
by Paulo Lee Ho, Yordanka Medina-Armenteros, Lívia Mendonça Munhoz Dati, Daniela Cajado-Carvalho, Christian Savio Silva, Pollyanna Fernandes Campos, Patrícia Antonia Estima Abreu, Júlia Tavares de Castro, Paulo Newton Tonolli, Mahyumi Fujimori, Rhubia Silveira Martins Rosa, Soledad Palameta, Michael Edward Miller, Vitor Anselmo Sakihara, Fernanda de Lima Valadares, Fabiana Lauretti Ferreira, Bianca Pereira Carvalho Holanda, Douglas Gonçalves de Macedo, Priscila Comone, Natully de Souza Suffert Fogaça, Alexandre Bimbo, Felipe Catanzaro De Moraes, Stephane Tereza Queiroz de Andrade, Helena Lage Ferreira, Edison Luiz Durigon, Clarice Weis Arns, Esper George Kallás, Milena Apetito Akamatsu and Ricardo das Neves Oliveiraadd Show full author list remove Hide full author list
Vaccines 2025, 13(6), 620; https://doi.org/10.3390/vaccines13060620 - 8 Jun 2025
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Abstract
Background/Objectives:H5N1 influenza viruses are spreading worldwide and threaten global public health. Preparedness is necessary to mitigate the worst-case scenario should an H5N1 influenza pandemic occur and justify the development of vaccines against circulating H5N1 viruses of concern. Methods: The production and characterization [...] Read more.
Background/Objectives:H5N1 influenza viruses are spreading worldwide and threaten global public health. Preparedness is necessary to mitigate the worst-case scenario should an H5N1 influenza pandemic occur and justify the development of vaccines against circulating H5N1 viruses of concern. Methods: The production and characterization of egg-based split and inactivated H5Nx of three distinct monovalent antigens from clades 2.3.4.4b, 2.3.2.1c, and 2.3.4 were performed at an industrial scale. These antigens were formulated and their immune responses, when combined or not with IB160 squalene-based oil-in-water emulsion adjuvant in a rat model, were evaluated in a one- or two-dose immunization schedule. IgG antibodies, hemagglutination inhibitions, and microneutralization titers were measured for vaccine-induced immunity and cross-reactivity. Results: Three monovalent vaccines from clades 2.3.4.4b, 2.3.2.1c, and 2.3.4 were produced at an industrial scale and characterized. The immune responses against the monovalent vaccines showed a clade-specific antibody response and the need to combine with IB160 adjuvant for a required immune response. Conclusions: Considering the candidate vaccine viruses (CVVs) with the testing potency reagents available and that the antibody response obtained against the CVVs produced was clade-specific, IDCDC RG-71A is the indicated CVV for the predominant currently circulating H5N1 influenza virus of clade 2.3.4.4b and must be combined with adjuvant to induce a higher and efficacious immune response in a two-dose immunization protocol. Full article
(This article belongs to the Special Issue Vaccine Development for Influenza Virus)
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15 pages, 1801 KiB  
Article
Immunity Against Mycobacterium avium Induced by DAR-901 and BCG
by Getahun Abate, Krystal A. Meza, Chase G. Colbert, Octavio Ramos-Espinosa, Nancy J. Phillips and Christopher S. Eickhoff
Vaccines 2025, 13(6), 619; https://doi.org/10.3390/vaccines13060619 - 7 Jun 2025
Viewed by 423
Abstract
Background: The prevalence of pulmonary nontuberculous mycobacteria (NTM) is increasing in Europe and North America. Most pulmonary NTM cases are caused by Mycobacterium avium complex (MAC). The treatment of pulmonary MAC is suboptimal with failure rates ranging from 30% to 40% and there [...] Read more.
Background: The prevalence of pulmonary nontuberculous mycobacteria (NTM) is increasing in Europe and North America. Most pulmonary NTM cases are caused by Mycobacterium avium complex (MAC). The treatment of pulmonary MAC is suboptimal with failure rates ranging from 30% to 40% and there is a need to develop new vaccines. Methods: We tested the ability of two whole-cell vaccines, DAR-901 (heat-killed M. obuense) and BCG (live-attenuated M. bovis), to induce MAC cross-reactive immunity by first immunizing BALB/c mice and then performing IFN-γ ELISPOT assays after overnight stimulation of splenocytes with live MAC. To study the ability of these vaccines to protect against MAC infection, BALB/c mice were vaccinated with DAR-901 (intradermal) or BCG (subcutaneous or intranasal) and challenged with aerosolized MAC 4 weeks later. A group of mice vaccinated with BCG were also treated with clarithromycin via gavage. Lung colony-forming units (CFU) in immunized mice and unvaccinated controls were quantified 4 weeks after infection. Histopathology was used to quantify lung inflammation and flow cytometry was used to study lung immunity in BCG-vaccinated and unvaccinated mice following MAC infection. To increase the safety profile of mucosal BCG vaccination, we studied BCG with a “kill switch” (tetR BCG) in scnn1b-transgenic mice (i.e., mice prone to cystic fibrosis-type lung diseases). Results: Our results showed that (i) DAR-901 induced cross-reactive immunity to MAC to a similar level as BCG, (ii) DAR-901 and BCG protected against aerosol MAC challenge, (iii) mucosal BCG vaccination, compared to systemic BCG and DAR-901 vaccinations, provided the best protection against MAC challenge, (iv) BCG vaccination did not interfere with anti-MAC activities of clarithromycin, (v) BCG-vaccinated mice had increased inflammation and increased frequencies of activated CD4 and CD8 T cells following MAC infection, and (vi) doxycycline treatment of tetR BCG-vaccinated mice decreased lung BCG CFU without affecting MAC immunity. Conclusions: Both DAR-901 and BCG vaccinations induce MAC cross-reactive immunity and protect against aerosolized MAC challenges. Mucosal BCG vaccination provides the best protection and TetR BCG could enhance the safety of mucosal BCG vaccination. Full article
(This article belongs to the Section Vaccines against Infectious Diseases)
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17 pages, 411 KiB  
Systematic Review
Immunity Awareness—Strategies to Improve the Degree of Acceptance of Vaccines: A Systematic Review
by Alejandro Martínez-Serrano, Montserrat Pulido-Fuentes, Blanca Notario-Pacheco, Ana María Palmar-Santos, Ana Isabel Cobo-Cuenca and Ana Díez-Fernández
Vaccines 2025, 13(6), 618; https://doi.org/10.3390/vaccines13060618 - 7 Jun 2025
Viewed by 412
Abstract
Background/Objectives: Vaccine hesitancy is one of the top ten threats to global health. It is necessary to develop appropriate strategies to address vaccine hesitancy. This systematic review aimed to analyze strategies used to improve the acceptance of vaccines, address doubts, and/or increase confidence [...] Read more.
Background/Objectives: Vaccine hesitancy is one of the top ten threats to global health. It is necessary to develop appropriate strategies to address vaccine hesitancy. This systematic review aimed to analyze strategies used to improve the acceptance of vaccines, address doubts, and/or increase confidence and motivation in routine vaccination across all age groups. Methods: A systematic review was conducted of the MEDLINE, Dialnet, Scielo, CINAHL, and CENTRAL databases between 2018 and 2023. The inclusion criterion was full-text studies in English or Spanish that improve the degree of acceptance of vaccines and were evaluated by vaccination rate or pre- or postintervention tests. For data extraction, each study was categorized as community education, tailored messages, media, and new technologies. Results: A total of 1938 studies were identified, 38 of which were selected. New technology-based interventions used in the adult population for several vaccines offer broad reach, user interaction, and data accessibility. Tailored message strategies were used mainly among parents to foster strong relationships through respectful and empathetic dialog. Community education programs were targeted mainly at adolescents, emphasizing the use of structured, appropriate and interactive materials. Media campaigns were used as a support strategy for community education and new technology strategies due to their simplicity, wide coverage, and reach. Conclusions: The best strategies for reducing hesitancy are multicomponent interventions with structured and organized educational content based on the reasons for hesitancy and tailored to the target population. Therefore, caution must be taken when applying interventions, given that no single strategy can address this issue. Full article
(This article belongs to the Special Issue Vaccination and Public Health in the 21st Century)
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