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Vaccines
Volume 13
Issue 5
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Vaccines, Volume 13, Issue 5 (May 2025) – 115 articles

Cover Story (view full-size image): Vaccines employing adenoviral (AdV) vector platforms such as human AdV (HAdV) and chimpanzee AdV (ChAdV) were pivotal in the fight against COVID-19. However, pre-existing vector immunity resulting from high natural prevalence and widespread use has limited their efficacy. The bovine AdV type 3 (BAdV-3) vector platform has emerged as a promising alternative in next-generation vaccine development. This platform offers key inherent attributes like high transduction efficiency, large transgene capacity, broad tissue tropism, suitability for intranasal administration, and strong innate and adaptive immune activation. Notably, it evades HAdV-specific immune responses and is nonpathogenic for its host. This review therefore explores the BAdV-3 vector’s potential as a versatile vaccine development platform for human and veterinary pathogens. View this paper
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22 pages, 3022 KiB  
Article
Circulating Antibodies Against Common Cold Coronaviruses Do Not Interfere with Immune Responses to Primary or Booster SARS-CoV-2 mRNA Vaccines
by Bindu Adhikari, Eugene M. Oltz, Richard J. Gumina, Maryssa K. Kick, Linda J. Saif and Anastasia N. Vlasova
Vaccines 2025, 13(5), 547; https://doi.org/10.3390/vaccines13050547 - 21 May 2025
Abstract
Background: Pre-existing cross-reactive antibodies (Abs) against common cold coronaviruses (CCCoVs) have been hypothesized to influence the immune responses to SARS-CoV-2 vaccine-induced Ab responses. Methods: Serum samples from healthy healthcare workers (HCWs, n = 64) receiving mRNA vaccines were collected at seven time points: [...] Read more.
Background: Pre-existing cross-reactive antibodies (Abs) against common cold coronaviruses (CCCoVs) have been hypothesized to influence the immune responses to SARS-CoV-2 vaccine-induced Ab responses. Methods: Serum samples from healthy healthcare workers (HCWs, n = 64) receiving mRNA vaccines were collected at seven time points: pre-COVID-19-vaccination (Pre), post-first dose (Vax1), post-second dose (Vax2), and 6-, 9-, 12-, and 15-months post-Vax2. Booster vaccine doses (n = 23) were received 1–80 days prior to the 9 m sample collection time point. We used peptide-based enzyme-linked immunosorbent assays (ELISAs) to measure SARS-CoV-2/CCCoV-specific IgG/IgA/IgM and SARS-CoV-2 IgG4 (associated with immune tolerance) Ab levels in the HCW serum samples. Additionally, we measured Epstein–Barr/influenza A (unrelated pathogens) virus-specific IgG Ab levels. Results: We observed that vaccination significantly increased SARS-CoV-2 IgG Ab levels at the Vax1 (p ≤ 0.0001) and Vax2 (p ≤ 0.0001) time points compared to Pre-Vax. These Ab levels declined at 6 months post-vaccination but increased again following the booster vaccine dose around the 9-month post-Vax2 time point in a cohort (n = 23) of the HCWs. However, this increase was modest compared to those induced by the primary vaccine series. Interestingly, a moderate but continuous increase in SARS-CoV-2 S IgG4 Ab levels was observed throughout this study, becoming statistically significant by the 15-month time point (p = 0.03). Further, a significant increase in CCCoV IgG (but not IgA/IgM) Ab levels was observed at the Vax1 time point, suggestive of cross-reactive or non-specific immune responses. Finally, we observed no negative correlation between the levels of pre-existing CCCoV-specific Abs and the vaccine-induced Ab response (Vax1/Vax2). Conclusions: Pre-existing CCCoV Abs do not interfere with the development of vaccine-induced immunity. However, vaccine-associated Abs wane over time, which may be associated with the increasing IgG4 Ab response. Full article
(This article belongs to the Section COVID-19 Vaccines and Vaccination)
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16 pages, 1014 KiB  
Review
Ocular Manifestations of Mpox and Other Poxvirus Infections: Clinical Insights and Emerging Therapeutic and Preventive Strategies
by Yuan Zong, Yaru Zou, Mingming Yang, Jing Zhang, Zizhen Ye, Jiaxin Deng, Kyoko Ohno-Matsui and Koju Kamoi
Vaccines 2025, 13(5), 546; https://doi.org/10.3390/vaccines13050546 - 21 May 2025
Abstract
Poxvirus infections, particularly those caused by the monkeypox virus, have emerged as significant public health threats. Ocular manifestations constitute a severe potential clinical complication associated with these infections, potentially resulting in permanent visual impairment in afflicted patients. This review aimed to examine the [...] Read more.
Poxvirus infections, particularly those caused by the monkeypox virus, have emerged as significant public health threats. Ocular manifestations constitute a severe potential clinical complication associated with these infections, potentially resulting in permanent visual impairment in afflicted patients. This review aimed to examine the clinical spectrum of ocular manifestations associated with mpox and other poxvirus infections and to evaluate current management strategies alongside emerging therapeutic interventions and prevention strategies. A comprehensive literature search was performed across major databases to identify studies reporting ocular involvement in poxviral infections. Ocular involvement in poxviral infections ranges from mild conjunctivitis and eyelid lesions to severe keratitis with potential vision loss. Mpox-related ocular manifestations are more prevalent in unvaccinated and immunocompromised individuals. Although early antiviral intervention and supportive care are critical, clinical outcomes vary considerably across viral clades. Emerging evidence indicates that tecovirimat may reduce lesion severity, although its impact on accelerating recovery remains limited. Moreover, vaccine strategies, particularly the MVA-BN (JYNNEOS) vaccine, appear to decrease ocular complications, despite regional disparities in access and implementation. Ocular complications pose a significant clinical challenge in mpox and related poxviral infections. This review highlights the need for early diagnosis and integrated treatment approaches that combine antiviral therapy, supportive care, and targeted vaccination. Further research is essential to refine treatment protocols and assess the long-term outcomes in diverse patient populations. Full article
(This article belongs to the Special Issue Strategies for the Monitoring, Treatment, and Prevention of Mpox and Other Poxvirus Infections)
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24 pages, 2758 KiB  
Article
A Modified Variant of Fasciola hepatica FhSAP-2 (mFhSAP-2) as a Recombinant Vaccine Candidate Induces High-Avidity IgG2c Antibodies and Enhances T Cell Activation in C57BL/6 Mice
by Riseilly Ramos-Nieves, Albersy Armina-Rodriguez, Maria Del Mar Figueroa-Gispert, Ghalib Figueroa-Quiñones, Carlimar Ocasio-Malavé and Ana M. Espino
Vaccines 2025, 13(5), 545; https://doi.org/10.3390/vaccines13050545 (registering DOI) - 20 May 2025
Abstract
Background/Objectives: In the past, FhSAP-2, an 11.5 kDa recombinant protein belonging to the Fasciola hepatica saposin-like/NK-lysin family, has been shown to induce over 60% partial protection in immunized rabbits and mice when challenged with F. hepatica metacercariae. However, despite FhSAP-2 being a promising [...] Read more.
Background/Objectives: In the past, FhSAP-2, an 11.5 kDa recombinant protein belonging to the Fasciola hepatica saposin-like/NK-lysin family, has been shown to induce over 60% partial protection in immunized rabbits and mice when challenged with F. hepatica metacercariae. However, despite FhSAP-2 being a promising vaccine candidate, its hydrophobic nature has made its purification a challenging process. The present study aimed to determine whether a modified 9.8 kDa variant of protein (mFhSAP-2), lacking a string of 16 hydrophobic amino acids at the amino terminus and a dominant Th1 epitope, could retain its immunogenic and Th1-inducing properties. Methods: RAW264.7 cells were stimulated with mFhSAP-2, and TNFα levels were determined. C57BL/6 mice were immunized with mFhSAP-2 alone or emulsified with Montanide ISA50. Total anti-mFhSAP-2 IgG subtypes, along with their avidity and titers, were measured using ELISA. The T cell proliferation index and levels of CD4+/CD8+ and IFNγ/IL-4 ratios were determined. Results: In vitro, mFhSAP-2 induced dose-dependent TNFα production in RAW264.7 cells. In vivo, mice immunized with mFhSAP-2 or mFhSAP-2+ISA50 developed high-avidity IgG2a and IgG2c antibodies at levels that were significantly higher than IgG1 antibody levels. However, the mFhSAP-2+ISA50 formulation induced higher and more homogenous antibody titers than mFhSAP-2, suggesting that an adjuvant may be required to enhance mFhSAP-2 immunogenicity. Immunization with mFhSAP-2+ISA50 also induced significantly higher activated CD4+/CD8+ T cell ratios and IFNγ/IL-4 ratios compared to naïve mice. Conclusions: Our results demonstrate that mFhSAP-2 retained its immunogenicity and Th1-polarizing properties, which were enhanced by the Montanide ISA50 adjuvant. The present study highlights the feasibility of inducing Th1-associated immune responses in mice using mFhSAP-2 as an antigen. Further studies are required to assess the potential application of the mFhSAP-2+ISA50 formulation as a vaccine against F. hepatica in natural hosts such as cattle and sheep, which could contribute to improved control and aid in the prevention and eradication of F. hepatica infection. Full article
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10 pages, 3228 KiB  
Article
Assessment of the Reversion to Virulence and Protective Efficacy in Pigs Receiving the Live Attenuated Classical Swine Fever Recombinant Vaccine Candidate FlagT4G
by Elizabeth Ramirez-Medina, Lauro Velazquez-Salinas, Alyssa Valladares, Ayushi Rai, Leeanna Burton, Leandro Sastre, Ediane Silva, Guillermo R. Risatti, Llilianne Ganges and Manuel V. Borca
Vaccines 2025, 13(5), 544; https://doi.org/10.3390/vaccines13050544 - 20 May 2025
Abstract
Background/Objectives: Control of classical swine fever virus (CSFV) in endemic countries relies on vaccination using live attenuated vaccines (LAVs). Most of these LAVs do not allow for the differentiation of vaccinated animals from infected animals (DIVA) based on their serological response. FlagT4G [...] Read more.
Background/Objectives: Control of classical swine fever virus (CSFV) in endemic countries relies on vaccination using live attenuated vaccines (LAVs). Most of these LAVs do not allow for the differentiation of vaccinated animals from infected animals (DIVA) based on their serological response. FlagT4G vaccine is a novel candidate that confers robust protective immunity early after vaccination and shows DIVA capabilities. Methods: This report presents the characterization of FlagT4G virus in terms of the stability of its genomic and attenuated phenotypes assessed by a reversion to virulence protocol, as well as its protective efficacy by determining the minimal protective dose. Results: Results presented here demonstrate that after five consecutive passages in groups of 5-week-old susceptible domestic pigs, FlagT4G virus remains genetically stable, and its attenuated phenotype remains unaltered. In terms of efficacy, FlagT4G virus induced solid protection against the intranasal challenge with 105 tissue culture infectious dose (TCID50) of virulent field isolate Brescia virus, even with a vaccine dose as low as 102 TCID50. Conclusions: Results presented here indicate that the FlagT4G vaccine may be a useful tool for CSFV control. Full article
(This article belongs to the Special Issue Veterinary Vaccines and Host Immune Responses)
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16 pages, 2352 KiB  
Article
XBB.1.5 RBD-Based Bivalent Vaccines Induced Antibody Responses Against SARS-CoV-2 Variants in Mice
by Jiawen Liu, Tiantian Wang, Hongying Ren, Ruixi Liu, Qian Wang, Jun Wu and Bo Liu
Vaccines 2025, 13(5), 543; https://doi.org/10.3390/vaccines13050543 - 20 May 2025
Abstract
(1) Background: The currently circulating variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibits resistance to antibodies induced by vaccines. The World Health Organization recommended the use of monovalent XBB.1 sublineages (e.g., XBB.1.5) as an antigenic component in 2023. (2) Objective: In [...] Read more.
(1) Background: The currently circulating variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibits resistance to antibodies induced by vaccines. The World Health Organization recommended the use of monovalent XBB.1 sublineages (e.g., XBB.1.5) as an antigenic component in 2023. (2) Objective: In this study, we aimed to develop vaccines based on the XBB.1.5 receptor-binding domain (RBD) to combat the recently emerged SARS-CoV-2 XBB and JN.1 variants, as well as previously circulating variants. (3) Methods: Glycoengineered Pichia pastoris was utilized to produce a recombinant XBB.1.5 RBD protein with mammalian-like and fucose-free N-glycosylation. The XBB.1.5 RBD was mixed with Al(OH)3:CpG adjuvants to prepare monovalent vaccines. Thereafter, the XBB.1.5 RBD was mixed with the Beta (B.1.351), Delta (B.1.617.2), or Omicron (BA.2) RBDs (1:1 ratio), along with Al(OH)3:CpG, to prepare bivalent vaccines. BALB/c mice were immunized with the monovalent and bivalent vaccines. Neutralizing antibody titers were assessed via pseudovirus and authentic virus assays; humoral immune responses were analyzed by RBD-binding IgG subtypes. (4) Results: The monovalent vaccine induced higher neutralizing antibody titers against Delta, BA.2, XBB.1.5, and JN.1 compared to those in mice immunized solely with Al(OH)3:CpG, as demonstrated by pseudovirus virus assays. The XBB.1.5/Delta RBD and XBB.1.5/Beta RBD-based bivalent vaccines provided potent protection against the BA.2, XBB.1.5, JN.1, and KP.2 variants, as well as the previously circulating Delta and Beta variants. All monovalent and bivalent vaccines induced high levels of RBD-binding IgG (IgG1, IgG2a, IgG2b, and IgG3) antibodies in mice, suggesting that they elicited robust humoral immune responses. The serum samples from mice immunized with the XBB.1.5 RBD-based and XBB.1.5/Delta RBD-based vaccines could neutralize the authentic XBB.1.16 virus. (5) Conclusions: The XBB.1.5/Beta and XBB.1.5/Delta RBD-based bivalent vaccines are considered as potential candidates for broad-spectrum vaccines against SARS-CoV-2 variants. Full article
(This article belongs to the Section COVID-19 Vaccines and Vaccination)
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16 pages, 1336 KiB  
Review
Malaria Vaccines: Current Achievements and Path Forward
by Jiayan Chen, Qi Wang, Xiaomeng He and Bei Yang
Vaccines 2025, 13(5), 542; https://doi.org/10.3390/vaccines13050542 - 19 May 2025
Abstract
Malaria remains a significant global health challenge. Although the recent approval of the liver-stage vaccines RTS, S and R21 marks significant progress in malaria control, challenges remain in achieving long-lasting and broad protection. In this review, we provide an overview of the current [...] Read more.
Malaria remains a significant global health challenge. Although the recent approval of the liver-stage vaccines RTS, S and R21 marks significant progress in malaria control, challenges remain in achieving long-lasting and broad protection. In this review, we provide an overview of the current landscape of malaria control, especially anti-malaria vaccine development. We first review the development of the RTS, S and R21 vaccines, highlighting their efficacy and limitations. We then examine other vaccines in development, including attenuated whole-sporozoite vaccines, as well as blood-stage-targeting vaccines and transmission-blocking vaccines targeting a variety of different immunogens. Additionally, we discuss emerging technologies, such as mRNA-based platforms, nanoparticle delivery systems, and novel adjuvants, assessing their potential to enhance the efficacy and mitigate the waning immunity concerns of most malaria vaccines. We believe that the identification of novel immunogen candidates, together with continued innovation in vaccine design and delivery, will enable us to win the fight against malaria in the future. Full article
(This article belongs to the Special Issue Vaccination Against Vector-Borne Diseases: Bridging Public Health and Epidemiology)
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14 pages, 1756 KiB  
Article
Pneumococcal Vaccine Uptake in Adults Before and After Hospitalization for Pneumococcal Infections in Hong Kong, 2015 to 2024
by King-Pui Florence Chan, Ting-Fung Ma, James Chung-Man Ho, Ivan Fan-Ngai Hung, Mary Sau-Man Ip and Pak-Leung Ho
Vaccines 2025, 13(5), 541; https://doi.org/10.3390/vaccines13050541 - 19 May 2025
Abstract
Background/Objectives: Vaccination is a key preventive measure against pneumococcal disease, but uptake rates remain low in high-risk populations. Limited information exists on pneumococcal vaccine uptake in individuals with a history of pneumococcal disease. This study aims to assess pneumococcal vaccine uptake and [...] Read more.
Background/Objectives: Vaccination is a key preventive measure against pneumococcal disease, but uptake rates remain low in high-risk populations. Limited information exists on pneumococcal vaccine uptake in individuals with a history of pneumococcal disease. This study aims to assess pneumococcal vaccine uptake and the factors associated with it in patients hospitalized for pneumococcal disease, before and after hospitalization, across time periods before, during, and after the COVID-19 pandemic. Methods: Data for patients aged ≥18 years who were hospitalized for pneumococcal disease between 2015 and 2024 were extracted from the Hospital Authority’s territory-wide electronic medical record database. The uptake of pneumococcal vaccines in subgroups aged 18–64 years and ≥65 years, with and without risk conditions, both before and after hospitalization for pneumococcal disease, was assessed, followed by multivariate analyses of the factors associated with vaccination uptake by logistic regression models. Results: This study included 5517 patients hospitalized for pneumococcal disease. Prior to hospitalization, the vaccination uptake among the eligible patients was 20.5%, with only 8.1% fully vaccinated, despite the majority (87.9%) having previous hospitalizations (subgroup medians 3–9 times) or outpatient clinic visits (subgroup median 61–107 times). After discharge, during a median follow-up of 1.85 years, almost all the eligible patients (98.4%) received subsequent inpatient (subgroup medians 3–4 times) and outpatient (subgroup medians 21–28 times) care, but only 32.2% of the eligible patients received the vaccine. Factors associated with increased vaccine uptake post-discharge included age ≥75 years (OR 1.6), ≥10 subsequent hospitalizations (OR 2.1), and ≥10 subsequent clinic visits (OR 55.9). Vaccination rates within 12 months post-discharge were significantly lower in the patients hospitalized during the COVID-19 pandemic (3.5%) compared to the baseline (11.6%) and post-COVID-19 (6.6%) periods. Conclusions: The uptake of the pneumococcal vaccine before hospitalization for pneumococcal disease was low and continued to be suboptimal post-discharge. Numerous vaccination opportunities were missed in both the inpatient and outpatient settings. These findings indicate a need to improve vaccination strategies. Full article
(This article belongs to the Section Epidemiology)
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15 pages, 602 KiB  
Article
Childhood Influenza Vaccination Is Not a Priority for Parents: A National, Cross-Sectional Survey of Barriers to Childhood Influenza Vaccination in Australia
by Maryke S. Steffens, Jessica Kaufman, Katarzyna T. Bolsewicz, Suzanna Vidmar, Maria Christou-Ergos, Majdi M. Sabahelzain, Julie Leask, Justin Boxall, Frank Beard and Margie Danchin
Vaccines 2025, 13(5), 540; https://doi.org/10.3390/vaccines13050540 - 19 May 2025
Abstract
Background/objectives: Influenza vaccines are recommended and free in Australia for children aged <5 years, but uptake remains low at 25.8% compared to the targets of 40% and 50%. National data on barriers hindering paediatric influenza vaccination can inform strategies to improve uptake. [...] Read more.
Background/objectives: Influenza vaccines are recommended and free in Australia for children aged <5 years, but uptake remains low at 25.8% compared to the targets of 40% and 50%. National data on barriers hindering paediatric influenza vaccination can inform strategies to improve uptake. The aim of this study was to measure barriers to influenza vaccination in Australian children aged <5 years. Methods: A national, cross-sectional survey of parents of children aged <5 years was conducted in March/April 2024. Parents were recruited using an online panel and asked about their intention to get an influenza vaccine for their youngest child in the upcoming influenza season. An adapted version of the validated Vaccine Barriers Assessment Tool measured 14 influenza vaccination barriers. Analysis assessed the prevalence of barriers and differences between parents intending to and those unsure or not intending to vaccinate by calculating the prevalence difference and 95% confidence interval. Results: A total of 2000 parents were recruited nationally. The most common barrier was parents feeling distressed when thinking about vaccinating their child against influenza (66.1% of intending parents, 65.6% of unsure/not intending parents). The barrier with the largest difference between intending and not intending/unsure parents was not prioritising their child’s influenza vaccination (47.2% vs. 6.1%, PD = 41.1 ppts, 95% CI: 35.9%, 46.3%). Other barriers with large differences were parents not feeling guilty if their unvaccinated child got influenza (41.5% vs. 7.5%, PD = 34.0 ppts, 95% CI: 28.8%, 39.1%) and parents not believing that influenza vaccines are effective (31.3% vs. 3.0%, PD = 28.2 ppts, 95% CI: 23.6%, 32.9%). Conclusions: Parents should be encouraged and supported to prioritise influenza vaccination alongside routine childhood vaccines in campaigns that emphasise disease risk and the importance, safety and effectiveness of influenza vaccination, and by optimising access to influenza vaccination. We recommend conducting similar surveys regularly to monitor trends in parental barriers to childhood influenza vaccination. Full article
(This article belongs to the Special Issue Vaccination Strategies for Global Public Health)
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15 pages, 739 KiB  
Brief Report
Persistent Low Anti-HIV Neutralizing Antibody Titers in HIV/HCV Coinfection Despite HCV Cure: A 5-Year Longitudinal Analysis
by Daniel Sepúlveda-Crespo, Víctor Sánchez-Merino, Rafael Amigot-Sánchez, Almudena Rubio-Pérez, Cristina Díez, Víctor Hontañón, Juan Berenguer, Juan González-García, Felipe García, Isidoro Martínez, Eloísa Yuste and Salvador Resino
Vaccines 2025, 13(5), 539; https://doi.org/10.3390/vaccines13050539 - 19 May 2025
Abstract
Background: Anti-HIV neutralizing antibodies (anti-HIV-nAbs) play a critical role in the immune defense against HIV by preventing viral entry and limiting replication. This study longitudinally evaluated the titers and variability of anti-HIV-nAbs in individuals coinfected with HIV and HCV. Samples were collected [...] Read more.
Background: Anti-HIV neutralizing antibodies (anti-HIV-nAbs) play a critical role in the immune defense against HIV by preventing viral entry and limiting replication. This study longitudinally evaluated the titers and variability of anti-HIV-nAbs in individuals coinfected with HIV and HCV. Samples were collected at three time points: before starting HCV treatment, one year after completion, and five years post-treatment. Methods: A retrospective analysis was conducted on 71 HIV/HCV-coinfected patients who achieved a sustained virologic response following antiviral therapy for HCV. A control group of 41 HIV-monoinfected individuals was also included. Anti-HIV-nAb titers were evaluated by HIV neutralization assays using a panel of six recombinant HIV viruses representing multiple genetic subtypes. Generalized Linear Mixed Models and Generalized Linear Models were used for statistical analysis. p-values were adjusted using the Benjamini–Hochberg procedure (q-value). Results: HIV-neutralizing antibody responses in HIV/HCV-coinfected individuals remained stable over five years following HCV therapy without significant changes (q-value > 0.05). The mean neutralization scores remained stable, with baseline scores of 6.1 (95% CI: 5.4–6.7), 6.2 (95% CI: 5.5–6.8) at one year post-HCV therapy, and 6.0 (95% CI: 5.3–6.7) at five years post-HCV therapy. HIV/HCV-coinfected individuals consistently showed lower neutralization scores compared to the control group throughout the follow-up (q-value < 0.05). Regression analyses adjusted for age, gender, nadir CD4+, and baseline CD4+ counts confirmed that the observed differences between HIV-monoinfected and HIV/HCV-coinfected individuals persisted (q-value < 0.05) at both the baseline and after HCV therapy completion. Conclusions: Successful HCV eradication in HIV/HCV-coinfected individuals did not normalize anti-HIV-nAb titers, which remained consistently lower than those in HIV-monoinfected controls over five years. Full article
(This article belongs to the Special Issue Vaccines and Vaccination: HIV, Hepatitis Viruses, and HPV)
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15 pages, 2579 KiB  
Article
Efficacy Evaluation of a VR-2332-Based Modified Live Vaccine Against NADC30-like PRRSV in China
by Lixin Li, Xiaxia Tong, Jianhong Shu, Huapeng Feng, Yanping Quan and Yulong He
Vaccines 2025, 13(5), 538; https://doi.org/10.3390/vaccines13050538 - 19 May 2025
Abstract
Background: Porcine reproductive and respiratory syndrome is caused by PRRSV. Modified live vaccines (MLVs) are widely used to control PRRSV infection, but their efficacy against the emerging NADC30-like variant remains unclear. This study aimed to evaluate the efficacy of a VR-2332-based MLV against [...] Read more.
Background: Porcine reproductive and respiratory syndrome is caused by PRRSV. Modified live vaccines (MLVs) are widely used to control PRRSV infection, but their efficacy against the emerging NADC30-like variant remains unclear. This study aimed to evaluate the efficacy of a VR-2332-based MLV against the NADC30-like PRRSV strain HNjz15. Methods: Forty piglets were randomized into a vaccination group (MLV group), negative control group (NC group), and sentinel group. MLV group piglets were immunized with a commercial MLV at 3 weeks of age and challenged with HNjz15 (106.6 TCID50/mL) at 21 days post-immunization. Clinical symptoms, viral load, antibody responses, cytokine levels, and lung lesions were monitored for 14 days post-challenge. Results: Although fever and respiratory symptoms were more pronounced in the NC group pigs than those of the MLV group (average percent occurrence: 65.2% vs. 52.9%), there was no statistical difference (p > 0.05) in the occurrence of respiratory symptoms between the two groups from 5 dpc. Reduced weight gains (by 40–53%) were also observed in the MLV and NC groups compared with the sentinels. The MLV and NC groups exhibited severe lung lesions, while there was no marked difference in viral RNA loads in serum and tissue samples between the MLV and NC groups (p > 0.05). The MLV vaccine induced a significant high level of N protein-specific antibodies compared to the NC group. There was also no significant difference in IFN-γ or TNF-α response to the HNjz15 challenge in both groups (p > 0.05). Conclusions: The VR-2332-based MLV does not provide adequate protection against challenge with the PRRSV-2 NADC30-like strain HNjz15. Full article
(This article belongs to the Section Vaccine Efficacy and Safety)
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17 pages, 1808 KiB  
Article
Impact of B18R-Encoding Messenger Ribonucleic Acid Co-Delivery on Neutralizing Antibody Production in Self-Amplifying Messenger Ribonucleic Acid Vaccines
by Yutao Wang, Lei Li, Min Liang, Gan Liu and Yinying Lu
Vaccines 2025, 13(5), 537; https://doi.org/10.3390/vaccines13050537 - 18 May 2025
Viewed by 85
Abstract
Objectives: The COVID-19 pandemic has brought mRNA vaccines to the forefront due to their widespread use. In this study, we explored the potential advantages of the self-amplifying mRNA (saRNA) vaccine over conventional mRNA vaccines. Methods: Initially, we optimized lipid nanoparticle formulations [...] Read more.
Objectives: The COVID-19 pandemic has brought mRNA vaccines to the forefront due to their widespread use. In this study, we explored the potential advantages of the self-amplifying mRNA (saRNA) vaccine over conventional mRNA vaccines. Methods: Initially, we optimized lipid nanoparticle formulations and employed dT20 affinity chromatography purification to improve the intracellular expression of saRNA. Subsequently, we demonstrated that saRNA exhibited sustained expression for up to one month, both in vitro and in vivo, in contrast to mRNA. Finally, we developed a saRNA-based COVID-19 vaccine and achieved superior immune protection in mice compared to mRNA vaccine by co-delivering the B18R-encoding mRNA. Results: The co-delivery of B18R-mRNA with the saRNA vaccine significantly enhanced neutralizing antibody responses, outperforming those induced by the mRNA vaccine alone. This co-delivery strategy effectively regulated the early innate immune activation triggered by saRNA, facilitating a more robust adaptive immune response. Conclusions: The optimization strategies we used in this study highlight the potential of saRNA vaccines to offer stronger and more durable immune protection. The insights gained from this study not only promote the advancement of saRNA vaccine development but also provide practical guidance for their broader application in the fight against infectious diseases. Full article
(This article belongs to the Special Issue Detection of SARS-CoV-2 Neutralizing Antibodies and Vaccine Development: 2nd Edition)
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17 pages, 2400 KiB  
Article
Generation of a Transgenic Plasmodium cynomolgi Parasite Expressing Plasmodium vivax Circumsporozoite Protein for Testing P. vivax CSP-Based Malaria Vaccines in Non-Human Primates
by Maya Aleshnick, Shreeya Hegde, Charlie Jennison, Sebastian A. Mikolajczak, Ashley M. Vaughan, Derek Haumpy, Thomas Martinson, Judith Straimer and Brandon K. Wilder
Vaccines 2025, 13(5), 536; https://doi.org/10.3390/vaccines13050536 - 17 May 2025
Viewed by 161
Abstract
Background/Objectives: Malaria, caused by infection with Plasmodium parasites, exacts a heavy toll worldwide. There are two licensed vaccines for malaria as well as two monoclonal antibodies that have shown promising efficacy in field trials. The vaccines and monoclonal antibodies target the major [...] Read more.
Background/Objectives: Malaria, caused by infection with Plasmodium parasites, exacts a heavy toll worldwide. There are two licensed vaccines for malaria as well as two monoclonal antibodies that have shown promising efficacy in field trials. The vaccines and monoclonal antibodies target the major surface protein (circumsporozoite protein, CSP) of Plasmodium falciparum. Yet P. falciparum is only one of the four major species of Plasmodium that infect humans. Plasmodium vivax is the second leading cause of malaria, but the P. vivax vaccine and monoclonal development lags far behind that for P. falciparum owing to the lack of basic preclinical tools such as in vitro culture or mouse models that replicate the key biological features of P. vivax. Notably among these features is the ability to form dormant liver stages (hypnozoites) that reactivate and drive the majority of the P. vivax malaria burden. Plasmodium cynomolgi is a simian parasite which is genotypically very close and phenotypically similar to P. vivax; it can infect non-human primates commonly used in research and replicates many features of P. vivax, including relapsing hypnozoites. Methods: Recently, a strain of P. cynomolgi has been adapted to in vitro cultures allowing parasite transgenesis. Here, we created a transgenic P. cynomolgi parasite in which the endogenous P. cynomolgi CSP has been replaced with P. vivax CSP, with the goal of enabling the preclinical study of anti-P. vivax CSP interventions to protect against primary and relapse infections. Results: We show that the in vitro-generated transgenic Pcy[PvCSP] parasite expresses both serotypes of P. vivax CSP and retains full functionality in vivo, including the ability to transmit to laboratory-reared Anopheles mosquitoes and cause relapsing infections in rhesus macaques. To our knowledge, this is the first gene replacement in a relapsing Plasmodium species. Conclusions: This work can directly enable the in vivo development of anti-P. vivax CSP interventions and provide a blueprint for the study of relapsing malaria through reverse genetics. Full article
(This article belongs to the Special Issue Recent Advances in Malaria Vaccine Development)
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14 pages, 2858 KiB  
Communication
Vaccine Confidence During Public Health Challenges and Prior to HPV Vaccine Introduction in Mali
by Tiffani Crippin, Karamoko Tounkara, Ibrahima Diarra, Pierre Kamate, Sarah Beseme, Matthew Murphy, Hayley Munir, Amalle Keita Daou, Garan Dabo, Ibrahima Téguété, Ousmane Koita and Anne S. De Groot
Vaccines 2025, 13(5), 535; https://doi.org/10.3390/vaccines13050535 - 17 May 2025
Viewed by 258
Abstract
Background/Objectives: Public health activities and the roll-out of new vaccines such as the HPV vaccine in Mali have been disrupted by both the COVID-19 pandemic and by political unrest from March 2020 until recently. The HPV vaccine was introduced into the childhood [...] Read more.
Background/Objectives: Public health activities and the roll-out of new vaccines such as the HPV vaccine in Mali have been disrupted by both the COVID-19 pandemic and by political unrest from March 2020 until recently. The HPV vaccine was introduced into the childhood vaccine program in 2024. Given the persistent threat of ongoing infectious disease epidemics, there is a pressing need to understand the factors influencing vaccine uptake in Mali and other low- and middle-income countries. Methods: To address this need, the GAIA Vaccine Foundation (GAIA VF), a nongovernmental organization (NGO), conducted a study of vaccine confidence in Bamako, the country’s capital and primary population center, between September 2021 and March 2022 at 12 community based primary care clinics and 1 rural primary care clinic. The study was coupled with a vaccine outreach and education campaign at each site. Results: Study staff collected information on vaccine confidence in surveys from 3445 community participants. Healthcare providers were also recruited from the 13 sites for vaccine-related training, and 140 of these participants completed pre- and post-surveys on their vaccine knowledge and confidence. Survey results indicate that community members trust their primary care providers more than they trust the government. However, primary care providers trust government sources of information more than other sources for guidance on vaccines. Conclusions: As new vaccines are introduced, engaging key healthcare leaders to inform healthcare providers and developing primary care provider-led community outreach will be critically important to gaining community confidence prior to and during vaccination campaigns in the future. Full article
(This article belongs to the Special Issue Vaccine Strategies for HPV-Related Cancers: 2nd Edition)
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13 pages, 214 KiB  
Review
Varicella and Zoster Vaccination Strategies in Immunosuppressed Pediatric Transplant Recipients
by Christopher Hartley, Priscila Villalba Davila, Emma Cole and Wikrom Karnsakul
Vaccines 2025, 13(5), 534; https://doi.org/10.3390/vaccines13050534 - 16 May 2025
Viewed by 69
Abstract
The varicella vaccine has prevented varicella in hundreds of thousands of patients since its establishment in 1974. It stimulates both humoral and cell-mediated immunity to produce an immune response that helps protect against the disease (not necessarily the infection). Serious sequala of varicella [...] Read more.
The varicella vaccine has prevented varicella in hundreds of thousands of patients since its establishment in 1974. It stimulates both humoral and cell-mediated immunity to produce an immune response that helps protect against the disease (not necessarily the infection). Serious sequala of varicella including pneumonia, hepatitis, and encephalitis can occur, with higher incidence in immunosuppressed individuals than in the general population. Patients who are not immunosuppressed should receive routine varicella vaccinations. For those who have not completed the series or are significantly distant from their last immunization, serologic testing may be considered. In pre-transplant patients, live-attenuated vaccines should ideally be administered at least four weeks before transplantation. Case studies have documented instances of patients requiring treatment for varicella after receiving a transplant within four weeks of vaccination. Full article
(This article belongs to the Special Issue Varicella and Zoster Vaccination)
19 pages, 1539 KiB  
Article
Evaluating the Impact of Needle-Free Delivery of Inactivated Polio Vaccine on Nigeria’s Routine Immunization Program: An Implementation Hybrid Trial
by Diwakar Mohan, Mercy Mvundura, Sidney Sampson, Victor Abiola Adepoju, Garba Bello Bakunawa, Chidinma Umebido, Adachi Ekeh, Joe Little, Catherine Daly, Christopher Morgan, Sunday Atobatele, Paul LaBarre and Elizabeth Oliveras
Vaccines 2025, 13(5), 533; https://doi.org/10.3390/vaccines13050533 - 16 May 2025
Viewed by 86
Abstract
Background/Objectives: The Tropis® ID device (PharmaJet®), a needle-free injection system, is a World Health Organization prequalified, hand-held device, which delivers intradermal injections without the use of needles and has previously been used for the delivery of fractional doses of [...] Read more.
Background/Objectives: The Tropis® ID device (PharmaJet®), a needle-free injection system, is a World Health Organization prequalified, hand-held device, which delivers intradermal injections without the use of needles and has previously been used for the delivery of fractional doses of inactivated polio vaccine (fIPV) in campaign and house-to-house settings. This implementation research study aimed to comparatively evaluate the vaccine coverage, cost, feasibility, and acceptability of using Tropis for fIPV for routine immunizations in two states in Nigeria (Kano and Oyo). Methods: The study included: (i) a cluster randomized trial (22 intervention facilities using Tropis for fIPV and 30 control facilities using the standard of care [SoC—full-dose IPV]) to assess the effectiveness in terms of improving the coverage of two doses of IPV, using a coverage survey involving 3433 children (aged 3–12 months); (ii) a pre- and post-implementation micro-costing evaluation involving the intervention facilities to estimate the costs; and (iii) mixed methods assessments (post-training assessment, provider survey, key informant interviews, and focus group discussions) to assess the feasibility and acceptability of fIPV delivery using Tropis. Results: The intention-to-treat analysis among the 3433 children surveyed did not show any difference between the intervention and control groups, primarily due to low compliance (approximately 50% of target beneficiaries reported Tropis use). The more relevant per protocol analysis, adjusting for lower compliance, showed that among those vaccinated with Tropis, second dose IPV coverage was 11.2% higher than the SoC. The delivery of fIPV using Tropis compared to the SoC resulted in incremental program cost savings, ranging from USD 0.07 to USD 1.00 per dose, administered across the scenarios evaluated. High acceptability was seen amongst caregivers (94%), and 95% of healthcare workers preferred Tropis over the SoC. Conclusions: Tropis is effective, feasible, acceptable, and saves costs when used as part of routine immunization programs. Full article
(This article belongs to the Special Issue Future Global Vaccination Strategies: Lessons from Early 21st Century Challenges)
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44 pages, 2372 KiB  
Review
Development of New Live-Attenuated Vaccine Candidates Lacking Antibody-Dependent Enhancement (ADE) Against Dengue
by Brandon E. K. Tan, Seng Kong Tham and Chit Laa Poh
Vaccines 2025, 13(5), 532; https://doi.org/10.3390/vaccines13050532 - 16 May 2025
Viewed by 70
Abstract
Dengue virus (DENV) threatens public health, especially in regions with tropical and subtropical climates. In 2024, the World Health Organisation reported 3.4 million confirmed dengue cases, with 16,000 severe cases and 3000 dengue-associated fatalities. The first licensed dengue vaccine, CYD-TDV (Dengvaxia®,Sanofi-Pasteur, [...] Read more.
Dengue virus (DENV) threatens public health, especially in regions with tropical and subtropical climates. In 2024, the World Health Organisation reported 3.4 million confirmed dengue cases, with 16,000 severe cases and 3000 dengue-associated fatalities. The first licensed dengue vaccine, CYD-TDV (Dengvaxia®,Sanofi-Pasteur, Paris, France), is recommended by the WHO only for individuals aged 9–45 years with a prior history of dengue infection. However, being vaccinated with Dengvaxia® increases the risk of developing severe dengue infections in seronegative individuals. Recently, a second licensed dengue vaccine, Qdenga®,Takeda, Singen, Germany), was approved and recommended by the WHO to be administered only in highly dengue-endemic countries, as it was not shown to elicit a robust immune response against DENV-3 and DENV-4 serotypes in dengue seronegative individuals. Due to an imbalance in immune response against all four DENV serotypes, there is a higher risk of developing the antibody-dependent enhancement (ADE) effect, which could lead to severe dengue. This review has identified mutations throughout the DENV genome that were demonstrated to attenuate the virulence of DENV in either in vitro or in vivo studies. Several amino acid residues within the DENV prM and E proteins were identified to play important roles in ADE and modifying these ADE-linked residues is important in the rational design of novel live-attenuated dengue vaccine candidates. This review provides current insights to guide the development of a novel live-attenuated tetravalent dengue vaccine candidate that is effective against all DENV serotypes and safe from ADE. The efficacy and safety of the live-attenuated vaccine candidate should be further validated in in vivo studies. Full article
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14 pages, 1731 KiB  
Article
COVID-19 Vaccination Enhances the Immunogenicity of Seasonal Influenza Vaccination in the Elderly
by Engin Berber, Fani Pantouli, Hannah B. Hanley and Ted M. Ross
Vaccines 2025, 13(5), 531; https://doi.org/10.3390/vaccines13050531 - 16 May 2025
Viewed by 56
Abstract
Background/Objectives: The co-circulation of both influenza viruses and SARS-CoV-2 poses a significant health risk, especially for the elderly. While vaccination against both diseases remains an effective strategy to reduce the burden of symptomatic infections, the effect of administering COVID-19 mRNA and seasonal influenza [...] Read more.
Background/Objectives: The co-circulation of both influenza viruses and SARS-CoV-2 poses a significant health risk, especially for the elderly. While vaccination against both diseases remains an effective strategy to reduce the burden of symptomatic infections, the effect of administering COVID-19 mRNA and seasonal influenza vaccines (COV-Flu) on elicited antibody responses has not been explored. Methods: Participants between 18 and 90 years old were vaccinated with COVID-19 mRNA vaccines (n = 67), seasonal influenza vaccines (n = 130), or both (n = 201) within a three-month period between 2021 and 2024. Serum hemagglutination-inhibition (HAI) titers against influenza A (H1N1, H3N2) and B (Yamagata, Victoria) strains were measured from the COV-Flu participants or the participants vaccinated with influenza vaccines only (mono-Flu). SARS-CoV-2 neutralization assays were performed on sera collected from the COV-Flu participants and the participants receiving the mRNA vaccine only (mono-COVID-19). Results: The administration of influenza virus vaccines and COVID-19 mRNA vaccines within a three-month period significantly enhanced the post-vaccination HAI titers against both influenza A and B vaccine components, particularly in the elderly (65–90) participants. There were no significant differences in SARS-CoV-2 neutralization titers in COV-Flu participants compared to mono-COVID-19 participants. Conclusions: Vaccination with both the COVID-19 mRNA and influenza vaccines enhances influenza-specific HAI titers without compromising the neutralization titers elicited by COVID-19 mRNA vaccination against SARS-CoV-2, especially in the elderly. These findings indicate the potential benefits of this approach, particularly for older adults, by boosting influenza virus vaccine-induced serum HAI activity while maintaining COVID-19 protective immunity. Full article
(This article belongs to the Special Issue The Effectiveness of Influenza Vaccine)
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16 pages, 2368 KiB  
Article
A Luciferase-Based Approach for Functional Screening of 5′ and 3′ Untranslated Regions of the mRNA Component for mRNA Vaccines
by Maria Rubtsova, Yuliana Mokrushina, Dmitry Andreev, Maria Poteshnova, Nikita Shepelev, Mariya Koryagina, Ekaterina Moiseeva, Diana Malabuiok, Yury Prokopenko, Stanislav Terekhov, Aleksander Chernov, Elena Vodovozova, Ivan Smirnov, Olga Dontsova, Alexander Gabibov and Yury Rubtsov
Vaccines 2025, 13(5), 530; https://doi.org/10.3390/vaccines13050530 - 16 May 2025
Viewed by 54
Abstract
Background/Objectives: The recent COVID-19 pandemic caused by SARS-CoV-2 infection has highlighted the need for protocols for rapid development of efficient screening methods to search for the optimal mRNA vaccine structures against mutable viral agents. The unmatched success of mRNA vaccines by Pfizer [...] Read more.
Background/Objectives: The recent COVID-19 pandemic caused by SARS-CoV-2 infection has highlighted the need for protocols for rapid development of efficient screening methods to search for the optimal mRNA vaccine structures against mutable viral agents. The unmatched success of mRNA vaccines by Pfizer and Moderna encoding the spike protein of SARS-CoV-2 confirms the potential of lipid nanoparticles for mRNA delivery for an accelerated development of new vaccines. The efficacy of vaccination and the production cost of mRNA-based vaccines largely depend on the composition of mRNA components, since the synthesis of an immunogenic protein requires precise and efficient translation in vivo. The composition of 5′ and 3′ UTR combinations of mRNA has a strong impact on the translation efficiency. The major objective of this study was to increase the probability of producing the immunogenic protein encoded by vaccine mRNA. For this purpose, we proposed to find a new combination of natural UTRs and, in parallel with that, to design and test the system for in vivo selection of translationally active UTRs. Methods: By using Ribo-Seq analysis, sets of candidate short UTRs were generated. These UTRs were tested both in cell cultures and in mice for effective production of secreted nanoluciferase (NLuc) and the S protein of SARS-CoV-2. A combination of the most effective UTRs was used to generate a prototype of an mRNA vaccine capable of inducing neutralizing antibodies against coronavirus. Results: The usefulness of the selected UTRs for vaccine development was tested by implicating the full-length coding sequence of SARS-CoV-2 S protein to produce the main immunogen. As a result, the system for functional screening of UTRs was created by using the NLuc gene. Conclusions: The proposed approach allows non-invasive quantitative assessment of the translational activity of UTRs in the blood serum of mice. By using the full-length sequence of SARS-CoV-2 S protein as a prototype, we demonstrated that the combination of UTRs selected using our luciferase-based reporter assay induces IgG titers and neutralization rates comparable to those obtained by using UTRs from commercial S-protein-based mRNA vaccines. Full article
(This article belongs to the Section DNA and mRNA Vaccines)
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6 pages, 153 KiB  
Editorial
Vaccine Hesitancy Through a Global Lens: Cross-Cultural Evidence from a Special Issue
by Gulzar H. Shah and Tran H. Nguyen
Vaccines 2025, 13(5), 529; https://doi.org/10.3390/vaccines13050529 - 16 May 2025
Viewed by 46
Abstract
Vaccine development in 1796 is among the most significant public health achievements, as it transformed global health by preventing epidemics and premature deaths, as well as eradicating life-threatening infectious diseases [...] Full article
(This article belongs to the Special Issue Vaccine Hesitancy)
15 pages, 2145 KiB  
Article
Single-Dose Intranasal Immunization with ChAd68-Vectored Prefusion F Vaccines Confers Sustained Protection Against Respiratory Syncytial Virus in Murine Models
by Jing Miao, Xuejie Li, Yingwen Li, Lingjing Mao, Wenkai Suo and Jiaming Lan
Vaccines 2025, 13(5), 528; https://doi.org/10.3390/vaccines13050528 - 15 May 2025
Viewed by 141
Abstract
Background/Objectives: Respiratory syncytial virus (RSV) poses a substantial global health threat, particularly impacting infants and vulnerable pediatric populations through severe respiratory morbidity. Methods: We developed a novel adenoviral vector vaccine platform utilizing chimpanzee adenovirus 68 (AdC68) to deliver prefusion F (pre-F) antigens from [...] Read more.
Background/Objectives: Respiratory syncytial virus (RSV) poses a substantial global health threat, particularly impacting infants and vulnerable pediatric populations through severe respiratory morbidity. Methods: We developed a novel adenoviral vector vaccine platform utilizing chimpanzee adenovirus 68 (AdC68) to deliver prefusion F (pre-F) antigens from RSV subtypes A and B, generating three vaccine candidates: AdC68-A (subtype A), AdC68-B (subtype B), and AdC68-A+B (bivalent formulation). Results: Single intranasal (i.n.) immunization and prime–boost immunizations via intramuscular (i.m.) routes in BALB/c mice induced robust immune activation, with single i.n. administration conferring durable protection evidenced by an 85% reduction in pulmonary viral loads (p < 0.05) at 134 days post-immunization. All vaccine formulations via i.n. single administration elicited potent subtype-specific IgG responses (geometric mean titers 50–12,800) and Th1-polarized cellular immunity (552–1201 IFN-γ+ spot-forming units/106 PBMCs, IgG2a/IgG1 > 1) in bivalent formulation group, while i.m. boosting enhanced cellular responses 3-fold versus prime immunization alone (p < 0.01). Notably, despite undetectable serum-neutralizing antibodies and absent mucosal IgA in bronchoalveolar lavage at 7 days post-i.n. immunization, the sustained viral control highlights non-neutralizing antibody-mediated protective mechanisms. Conclusions: These findings establish the proof-of-concept for adenoviral-vectored intranasal vaccines against RSV, though optimization of humoral response induction and mucosal immunity duration require further investigation. Full article
(This article belongs to the Special Issue Strategies of Viral Vectors for Vaccine Development)
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12 pages, 977 KiB  
Article
Is Brazil Reversing the Decline in Childhood Immunization Coverage in the Post-COVID-19 Era? An Interrupted Time Series Analysis
by Ramon Costa Saavedra, Rita Carvalho-Sauer, Enny S. Paixao, Maria Yury Travassos Ichihara, Maria da Conceição Nascimento Costa and Maria da Glória Teixeira
Vaccines 2025, 13(5), 527; https://doi.org/10.3390/vaccines13050527 - 15 May 2025
Viewed by 142
Abstract
Background: The COVID-19 pandemic had significant impacts on healthcare systems, including the disruption of essential services such as childhood immunization. Containment measures, such as social distancing, contributed to reduced adherence to vaccination programs, increasing the risk of re-emerging vaccine-preventable diseases. We aim [...] Read more.
Background: The COVID-19 pandemic had significant impacts on healthcare systems, including the disruption of essential services such as childhood immunization. Containment measures, such as social distancing, contributed to reduced adherence to vaccination programs, increasing the risk of re-emerging vaccine-preventable diseases. We aim to assess the evolution of childhood vaccination coverage in Brazil from 2010 to 2024, identifying trends before, during, and after the COVID-19 pandemic. Methods: An interrupted time series (ITS) study was conducted using publicly available aggregated data on vaccination coverage for children under one year of age. Prais–Winsten regression models were applied to estimate trend changes and evaluate the impact of the pandemic on immunization levels. Results: The findings indicate a progressive decline in vaccination coverage between 2010 and 2019, which was intensified in 2020 by the pandemic. The BCG vaccine showed the greatest decline (−24.88%, p < 0.001), while pentavalent and hepatitis B vaccines decreased annually by −3.72% and −2.21%, respectively. From 2021 onwards, a gradual recovery in coverage was observed, with significant increases for BCG (+7.48% per year, p < 0.001), hepatitis B (+7.45%, p = 0.014), and MMR (+6.73%, p = 0.017) vaccines. Discussion: The results highlight a concerning decline in childhood immunization, exacerbated by the pandemic but showing recent signs of recovery. This scenario underscores structural challenges within the National Immunization Program, requiring coordinated efforts to reverse vaccination losses and ensure system resilience in the face of future crises. Full article
(This article belongs to the Special Issue Understanding Infectious Disease Vaccinations: Implications for Health and Safety)
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20 pages, 290 KiB  
Review
Helicobacter pylori Vaccine: Mechanism of Pathogenesis, Immune Evasion and Analysis of Vaccine Types
by Jingwen Gong, Qing Wang, Xing Chen and Junhui Lu
Vaccines 2025, 13(5), 526; https://doi.org/10.3390/vaccines13050526 - 15 May 2025
Viewed by 165
Abstract
Helicobacter pylori (H. pylori) is a gram-negative, spiral-shaped bacterium that colonizes the human gastric mucosa, leading to various gastric diseases. H. pylori infection has become a pressing public health issue that affects more than 50% of the human population worldwide, almost 40 years [...] Read more.
Helicobacter pylori (H. pylori) is a gram-negative, spiral-shaped bacterium that colonizes the human gastric mucosa, leading to various gastric diseases. H. pylori infection has become a pressing public health issue that affects more than 50% of the human population worldwide, almost 40 years after its discovery. Traditional treatments, based on the use of bismuth-based triple and quadruple therapies, are effective while facing a series of problems, such as difficulty in patient compliance, the rise of antibiotic resistance, and possible recurrence of infection. Therefore, the development of an efficacious vaccine against H. pylori would be extremely urgent. This review mainly elaborates on the pathogenic mechanism and immune evasion mechanism of H. pylori, as well as various strategies adopted in vaccine development, including whole-cell vaccines, subunit vaccines, DNA vaccines, and live vector vaccines. Animal studies and clinical trials demonstrate that H. pylori vaccines significantly reduce bacterial load and provide cellular immunity over some time. Multiple studies have clarified the advantages and limitations of each candidate vaccine. Although the development of H. pylori vaccines provides benefits to reduce the global burden, there are still significant challenges to developing vaccines in safety, efficacy, and availability. Overcoming these challenges, along with the advancement of vaccine technology, can better prevent and treat H. pylori infection. Full article
(This article belongs to the Section Clinical Immunology)
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11 pages, 2051 KiB  
Article
Identification and Validation of Th1-Selective Epitopes Derived from Proteins Overexpressed in Breast Cancer Stem Cells
by Denise L. Cecil, Daniel Herendeen, Meredith Slota, Megan M. O’Meara, Yushe Dang, Lauren Corulli and Mary L. Disis
Vaccines 2025, 13(5), 525; https://doi.org/10.3390/vaccines13050525 - 15 May 2025
Viewed by 184
Abstract
Background: Breast cancer stem cells (CSCs), particularly those enriched in triple-negative breast cancer (TNBC), are key contributors to tumor recurrence, metastasis, and resistance to therapy. CSCs often undergo epithelial-to-mesenchymal transformation (EMT), enhancing their invasiveness. Immune-based strategies that selectively target CSC/EMT antigens offer a [...] Read more.
Background: Breast cancer stem cells (CSCs), particularly those enriched in triple-negative breast cancer (TNBC), are key contributors to tumor recurrence, metastasis, and resistance to therapy. CSCs often undergo epithelial-to-mesenchymal transformation (EMT), enhancing their invasiveness. Immune-based strategies that selectively target CSC/EMT antigens offer a promising therapeutic approach. Methods: Twelve candidate CSC/EMT-associated proteins were identified through a systematic literature review. Human serum samples were assessed for antigen-specific IgG using ELISA. Th1/Th2 cytokine profiles, in response to predicted MHC II epitopes, were measured by ELISPOT in PBMCs. Epitope immunogenicity and tumor inhibition were evaluated in murine models, using either TNBC or luminal B syngeneic breast cancer cell lines. Results: Six of the candidate proteins (SOX2, YB1, FOXQ1, MDM2, CDH3, CD105) elicited antigen-specific IgG in human serum. Th1-selective epitopes, defined by high Th1/Th2 ratios, were identified for five of these proteins. Immunization of mice with peptide pools derived from CD105, CDH3, MDM2, SOX2, and YB1 induced significant antigen-specific IFN-γ responses. Tumor growth was significantly inhibited in the vaccinated mice across both the TNBC and luminal B breast cancer models, with mean tumor volume reductions ranging from 61% to 70%. Conclusions: CSC/EMT-associated antigens are immunogenic in humans and can be targeted using Th1-selective epitope-based vaccines. Immunization with these epitopes effectively inhibits tumor growth in multiple murine models of breast cancer. These findings support further clinical evaluation of CSC/EMT-targeted vaccines, especially for high-risk or advanced-stage breast cancer patients. Full article
(This article belongs to the Special Issue Vaccines Targeting the Tumor Microenvironment: Challenges and Future Prospects)
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20 pages, 986 KiB  
Review
Past, Present, and Future of Viral Vector Vaccine Platforms: A Comprehensive Review
by Justin Tang, Md Al Amin and Jian L. Campian
Vaccines 2025, 13(5), 524; https://doi.org/10.3390/vaccines13050524 - 15 May 2025
Viewed by 261
Abstract
Over the past several decades, viral vector-based vaccines have emerged as some of the most versatile and potent platforms in modern vaccinology. Their capacity to deliver genetic material encoding target antigens directly into host cells enables strong cellular and humoral immune responses, often [...] Read more.
Over the past several decades, viral vector-based vaccines have emerged as some of the most versatile and potent platforms in modern vaccinology. Their capacity to deliver genetic material encoding target antigens directly into host cells enables strong cellular and humoral immune responses, often superior to what traditional inactivated or subunit vaccines can achieve. This has accelerated their application to a wide array of pathogens and disease targets, from well-established threats like HIV and malaria to emerging infections such as Ebola, Zika, and SARS-CoV-2. The COVID-19 pandemic further highlighted the agility of viral vector platforms, with several adenovirus-based vaccines quickly authorized and deployed on a global scale. Despite these advances, significant challenges remain. One major hurdle is pre-existing immunity against commonly used vector backbones, which can blunt vaccine immunogenicity. Rare but serious adverse events, including vector-associated inflammatory responses and conditions like vaccine-induced immune thrombotic thrombocytopenia (VITT), have raised important safety considerations. Additionally, scaling up manufacturing, ensuring consistency in large-scale production, meeting rigorous regulatory standards, and maintaining equitable global access to these vaccines present profound logistical and ethical dilemmas. In response to these challenges, the field is evolving rapidly. Sophisticated engineering strategies, such as integrase-defective lentiviral vectors, insect-specific flaviviruses, chimeric capsids to evade neutralizing antibodies, and plug-and-play self-amplifying RNA approaches, seek to bolster safety, enhance immunogenicity, circumvent pre-existing immunity, and streamline production. Lessons learned from the COVID-19 pandemic and prior outbreaks are guiding the development of platform-based approaches designed for rapid deployment during future public health emergencies. This review provides an exhaustive, in-depth examination of the historical evolution, immunobiological principles, current platforms, manufacturing complexities, regulatory frameworks, known safety issues, and future directions for viral vector-based vaccines. Full article
(This article belongs to the Special Issue Strategies of Viral Vectors for Vaccine Development)
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18 pages, 4923 KiB  
Article
A Computationally Designed Prefusion Stabilized Human Metapneumovirus Fusion Protein Vaccine Antigen Elicited a Potent Neutralization Response
by Michael Kishko, Antonia Stuebler, Sukanya Sasmal, Yvonne Chan, Dean Huang, Christopher Reyes, Jasmine Lin, Owen Price, Ana Kume, Katie Zong, Christine Bricault, Judith Alamares-Sapuay and Linong Zhang
Vaccines 2025, 13(5), 523; https://doi.org/10.3390/vaccines13050523 - 15 May 2025
Viewed by 283
Abstract
Background/Objectives: Human metapneumovirus (hMPV) is a leading cause of respiratory infections in the elderly, with high morbidity and mortality and with no vaccines or specific therapies available. The primary protective antigen of hMPV is the fusion protein, and its prefusion conformation (pre-F) is [...] Read more.
Background/Objectives: Human metapneumovirus (hMPV) is a leading cause of respiratory infections in the elderly, with high morbidity and mortality and with no vaccines or specific therapies available. The primary protective antigen of hMPV is the fusion protein, and its prefusion conformation (pre-F) is considered the most promising target for vaccine development. Methods: Utilizing computational design strategies focused on intraprotomer interface stabilization, we designed hMPV pre-F recombinant subunit vaccine candidates based on the most prevalent A2 subtype and characterized them in vitro and in vivo, benchmarking to the prototypical hMPV pre-F stabilized by an introduction of a proline at site 185. Results: The top candidate (N46V_T160F) yielded 14.4 mg/L with a melting temperature of 79.3 °C as compared to 5.7 mg/L and 70.4 °C for the benchmark. By employing monoclonal antibody binding to all six antigenic sites of hMPV pre-F, we confirmed this construct retained all pre-F specific antigenic sites and that the key sites Ø and V were stable at 4 °C for up to 6 months. When immunogenicity of N46V_T160F was evaluated in mice, it induced higher binding and neutralizing antibody titers than the benchmark, which stemmed in part from increased levels of site Ø and site II targeting Abs. Further, this A2 based construct induced cross-neutralizing Abs against all four hMPV subtypes. Lastly, our construct exhibited similar immunogenicity as the recently published next-generation hMPV pre-F constructs, DS-CavEs2 and v3B_Δ12_D454C-V458C. Conclusions: N46V_T160F is a promising hMPV vaccine candidate paving the way for further development and optimization. Full article
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14 pages, 920 KiB  
Review
Is Influenza Vaccination Our Best ‘Shot’ at Preventing MACE? Review of Current Evidence, Underlying Mechanisms, and Future Directions
by Alexia El Khoury, Joy Abou Farah and Elie Saade
Vaccines 2025, 13(5), 522; https://doi.org/10.3390/vaccines13050522 - 14 May 2025
Viewed by 216
Abstract
Background: Major adverse cardiovascular events (MACE), including myocardial infarction, stroke, and cardiovascular death, are the leading contributors to global morbidity and mortality worldwide. Accumulating evidence suggests a strong association between influenza infection and increased risk of MACE, especially in high-risk populations. Influenza vaccination [...] Read more.
Background: Major adverse cardiovascular events (MACE), including myocardial infarction, stroke, and cardiovascular death, are the leading contributors to global morbidity and mortality worldwide. Accumulating evidence suggests a strong association between influenza infection and increased risk of MACE, especially in high-risk populations. Influenza vaccination has been proposed as a potential strategy for reducing this risk by mitigating systemic inflammation and preventing atherosclerotic plaque destabilization, although the precise mechanisms remain under investigation. Results: Multiple meta-analyses and RCTs suggest that influenza vaccination is associated with a reduced risk of MACE, particularly in high-risk individuals with preexisting cardiovascular disease, but the results are less consistent for primary prevention in low-risk populations. The current data support the importance of early and annual vaccination for optimizing cardiovascular outcomes. Conclusions: Influenza vaccination is emerging as an effective and accessible strategy to reduce the risk of major adverse cardiovascular events, particularly in high-risk individuals. While further research is needed to clarify its role in low-risk populations and the underlying mechanisms of protection, current evidence supports its integration into cardiovascular preventive care. Full article
(This article belongs to the Special Issue Vaccines and Vaccine Preventable Diseases)
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20 pages, 1791 KiB  
Review
Clinical and Fundamental Research Progressions on Tumor-Infiltrating Lymphocytes Therapy in Cancer
by Jiandong Hu, Mengli Jin, Weihong Feng, Barbara Nassif-Rausseo, Alexandre Reuben, Chunhua Ma, Gregory Lizee and Fenge Li
Vaccines 2025, 13(5), 521; https://doi.org/10.3390/vaccines13050521 - 14 May 2025
Viewed by 234
Abstract
Malignant tumors represent a significant threat to human health. Among the various therapeutic strategies available, cancer immunotherapy—encompassing adoptive cell transfer (ACT) and immune checkpoint blockade therapy—has emerged as a particularly promising approach following surgical resection, radiotherapy, chemotherapy, and molecular targeted therapies. This form [...] Read more.
Malignant tumors represent a significant threat to human health. Among the various therapeutic strategies available, cancer immunotherapy—encompassing adoptive cell transfer (ACT) and immune checkpoint blockade therapy—has emerged as a particularly promising approach following surgical resection, radiotherapy, chemotherapy, and molecular targeted therapies. This form of treatment elicits substantial antigen-specific immune responses, enhances or restores anti-tumor immunity, thereby facilitating the control and destruction of tumor cells, and yielding durable responses across a range of cancers, which can lead to the eradication of tumor lesions and the prevention of recurrence. Tumor-infiltrating lymphocytes (TILs), a subset of ACT, are characterized by their heterogeneity and are found within tumor tissues, where they play a crucial role in mediating host antigen-specific immune responses against tumors. This review aims to explore recent advancements in the understanding of TILs biology, their prognostic implications, and their predictive value in therapeutic contexts. Full article
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13 pages, 1177 KiB  
Article
Differences in Mpox and Vaccinia Immunity Induced by Non-Replicating and Replicating Vaccinia-Based Vaccines
by Getahun Abate, Krystal Meza, Yinyi Yu, Chase Colbert, Anna Jaunarajs, Azra Blazevic, Daniel F. Hoft and Sharon E. Frey
Vaccines 2025, 13(5), 520; https://doi.org/10.3390/vaccines13050520 - 14 May 2025
Viewed by 163
Abstract
Background: The recent global outbreak with clade IIb and the concurrent emergence of clade I mpox virus in Africa show that mpox is a challenging problem. MVA-BN induces low-level mpox-neutralizing antibody responses that wane rapidly. This study was conducted to compare the [...] Read more.
Background: The recent global outbreak with clade IIb and the concurrent emergence of clade I mpox virus in Africa show that mpox is a challenging problem. MVA-BN induces low-level mpox-neutralizing antibody responses that wane rapidly. This study was conducted to compare the mpox immunity induced by a replication-competent smallpox vaccine and non-replicating MVA-BN. Methods: Stored sera (n = 302) and PBMCs (n = 244) collected pre-vaccination and at five post-vaccination time points in MVA-BN and six post-vaccination time points in Dryvax clinical trials were used. Antibody titers that neutralized at least 50% of mpox in cell culture were determined by the focus reduction neutralization test (FRNT) 50, and the mpox-specific T cell responses were measured using an IFN-γ ELISPOT assay. Results: The peak geometric fold rise (95% CI) (i.e., the maximum GMFR across all study visits) in the mpox FRNT50 for subcutaneous (SC) MVA-BN, intradermal (ID) MVA-BN, and Dryvax was 22.1 (8.3, 59.1), 18.5 (8.0, 43.1), and 245.8 (100.4, 601.6), respectively. The GMFR at day 180 post-vaccination for MVA-BN (SC), MVA-BN (ID), and Dryvax was 2.4, 2.7, and 64, respectively. The mean (95% CI) peak number of mpox-specific IFN-γ-producing SFCs was 127 (43.1, 238.3), 87.3 (46, 137), and 61.2 (44.3, 77.7) for MVA-BN (SC), MVA-BN (ID), and Dryvax, respectively. On day 180, the mean SFCs in the three groups decreased to 10.8 (−34.4, 3.8), 3.3 (−6.2, 18.6), and 2.2 (−9, 12.5), respectively. Conclusions: The peak mpox-neutralizing antibody titer was >10-fold lower in MVA-BN recipients compared to those who received a replication-competent smallpox vaccine, and the level at day 180 was >20 times lower in MVA-BN recipients. MVA-BN induced similar or higher T cell responses. Full article
(This article belongs to the Section Vaccines against Tropical and other Infectious Diseases)
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21 pages, 2225 KiB  
Article
Allocation of Oral Cholera Vaccines in Africa
by Elisa M. Maffioli and Yutong Lu
Vaccines 2025, 13(5), 519; https://doi.org/10.3390/vaccines13050519 - 14 May 2025
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Abstract
Objectives: In this study, we examine the allocation of oral cholera vaccines (OCVs) across 25 African countries between 2013 and 2019. Methods: We constructed a dataset combining cholera outbreaks and requests, decisions, and deliveries of OCVs from the Global Task Force on Cholera [...] Read more.
Objectives: In this study, we examine the allocation of oral cholera vaccines (OCVs) across 25 African countries between 2013 and 2019. Methods: We constructed a dataset combining cholera outbreaks and requests, decisions, and deliveries of OCVs from the Global Task Force on Cholera Control, alongside additional covariates. Using machine learning algorithms, we assess the relative importance of socio-demographic, governance, and weather variables in predicting cholera outbreaks. We constructed and used an “index of cholera risk” as an instrumental variable to predict the likelihood of suspected cases and estimate the impact of cholera outbreaks on OCV allocation. Results: The majority of OCVs (77.4%) were allocated reactively. Governments took an average of 299.6 days to request doses, international agencies took 10.4 days to decide, and it took 84 days for vaccines to be delivered. Countries experiencing a cholera outbreak were 31.7 and 36.5 percentage points more likely to request and receive a vaccine delivery in the same month as the outbreak, respectively. We confirmed that the probability of obtaining vaccines through a reactive mechanism was 48.4 percentage points higher compared to preventive allocation. When exploring the heterogeneity of impacts, OCVs were more likely to be requested, allocated, and delivered in countries with strong institutions and those not facing crisis situations. OCVs were also more likely to be allocated in the central parts of the continent. Conclusions: While OCV allocation is responsive to cholera outbreaks, addressing delays, particularly in high-risk countries, could improve their distribution and mitigate the impact of cholera outbreaks. This study highlights the need for targeted strategies to ensure vaccine access in fragile and conflict-affected settings, where institutional capacity is weaker. Full article
(This article belongs to the Section Human Vaccines and Public Health)
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14 pages, 867 KiB  
Brief Report
Serological Correlate of Protection Established by Neutralizing Antibodies Differs Among Dialysis Patients with SARS-CoV-2 Variants of Concern
by Guy Rostoker, Stéphanie Rouanet, Myriam Merzoug, Hiba Chakaroun, Mireille Griuncelli, Christelle Loridon, Ghada Boulahia and Luc Gagnon
Vaccines 2025, 13(5), 518; https://doi.org/10.3390/vaccines13050518 - 13 May 2025
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Abstract
Background: The 2019 coronavirus disease (COVID-19) pandemic had a severe impact on frail, end-stage kidney disease (ESKD) patients, either on dialysis or transplanted, with a high mortality rate in the early waves. Vaccination against SARS-CoV-2 with mRNA vaccines has led to reduced hospitalization [...] Read more.
Background: The 2019 coronavirus disease (COVID-19) pandemic had a severe impact on frail, end-stage kidney disease (ESKD) patients, either on dialysis or transplanted, with a high mortality rate in the early waves. Vaccination against SARS-CoV-2 with mRNA vaccines has led to reduced hospitalization and mortality rates in the general population and ESKD patients. Neutralizing antibodies (NAbs) are a valuable correlate of protection after vaccination, and IgG anti-spike antibodies are considered a surrogate marker of protection. Methods: This study investigated the correlates of protection brought by NAb and anti-spike IgG antibodies against SARS-CoV-2 wild-type Wuhan strain and variants of concern in a cohort of 128 French patients on dialysis after vaccination with the BNT162b2 mRNA vaccine. The correlate was assessed using Receiver Operating Characteristic curves. Results: The level of protection for IgG anti-spike antibodies was set at 917 BAU/mL for the original Wuhan strain and 980 BAU/mL and 1450 BAU/mL, respectively, for the Delta and Omicron BA.1 variants. Conclusions: The level of protection can be regularly monitored by measuring IgG anti-spike antibody concentrations to allow tailored boosters of SARS-CoV-2 vaccination in this frail and immunocompromised ESKD population. Full article
(This article belongs to the Special Issue SARS-CoV-2 Variants, Vaccines, and Immune Responses)
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