Vaccines

17 pages, 312 KiB

Open AccessReview

Human Alpha Herpesviruses Infections (HSV1, HSV2, and VZV), Alzheimer’s Disease, and the Potential Benefits of Targeted Treatment or Vaccination—A Virological Perspective

by Peter A. C. Maple and Akram A. Hosseini

Vaccines 2025, 13(6), 572; https://doi.org/10.3390/vaccines13060572 (registering DOI) - 27 May 2025

Abstract

Understanding the contribution of human herpesviruses to the aetiology of neurodegenerative diseases is an emerging field of interest. The association of Epstein–Barr virus with multiple sclerosis is the most researched example; however, the definitive proof of causation is still lacking. Alzheimer’s disease (AD) [...] Read more.

Understanding the contribution of human herpesviruses to the aetiology of neurodegenerative diseases is an emerging field of interest. The association of Epstein–Barr virus with multiple sclerosis is the most researched example; however, the definitive proof of causation is still lacking. Alzheimer’s disease (AD) is the most common form of dementia and typically manifests in individuals aged over 65 years; however, it also occurs in a small number of individuals aged less than 65 years. A combination of environmental, genetic, and lifestyle factors is believed to contribute to the development of AD. There have been several reports describing potential associations of infections or reactivations of human alphaherpesviruses with AD. A particular characteristic of human alphaherpesviruses (herpes simplex viruses 1 and 2, varicella zoster virus) is that they are neurotropic and that lifelong infection (latency) is established mainly in the dorsal root and trigeminal ganglia. There have also been reports that suppression of alphaherpesvirus infections through either vaccination or the application of antiviral treatments may be protective against the development of AD. Zoster vaccines and acyclovir may prove to be effective interventions for preventing or limiting the progression of AD. This is particularly relevant as there are currently no available cheap and effective treatments for AD. In this review, the basic virology of human alphaherpesviruses is described followed by their epidemiology and associations with AD. Finally, the prevention and treatment of human alphaherpesviruses are considered in the context of potential applications for the prevention of AD. Full article

(This article belongs to the Special Issue Varicella and Zoster Vaccination)

19 pages, 8334 KiB

Open AccessArticle

Construction and Preclinical Evaluation of a Recombinant Attenuated Measles Vaccine Candidate of the H1a Genotype

by Lixia Xie, Yuanbao Liu, Yajing Zhang, Biao Niu, Hui Wang, Yue Guo, Jinliang Wang, Juncheng Ruan, Guandong Xie, Zhiguo Wang, Zhenfang Fu, Qi An and Dayong Tian

Vaccines 2025, 13(6), 571; https://doi.org/10.3390/vaccines13060571 (registering DOI) - 27 May 2025

Abstract

Background: Measles, an acute respiratory infectious disease caused by the measles virus, continues to pose a significant threat to children under five years old worldwide. Despite the availability of effective vaccines, challenges such as insufficient vaccination coverage and antigenic drift contribute to [...] Read more.

Background: Measles, an acute respiratory infectious disease caused by the measles virus, continues to pose a significant threat to children under five years old worldwide. Despite the availability of effective vaccines, challenges such as insufficient vaccination coverage and antigenic drift contribute to its persistence. Based on a newly isolated wild-type measles virus strain (genotype H1a), designated MVs/Jiangsu.CHN/38.16/1[H1a] (MV-1), this study aims to develop and evaluate a novel recombinant measles virus vaccine candidate designed to enhance immunogenicity and broaden protection against multiple epidemic genotypes. Methods: A recombinant measles virus vaccine candidate, designated rSchwarz/FH(H1a), was developed by incorporating immunogenic genes from the H1a genotype into the backbone of the Schwarz vaccine strain. The genetic stability, safety, and immunogenicity of this vaccine candidate were evaluated in preclinical models. Relevant sample sizes and methodologies were selected to ensure comprehensive assessment of vaccine efficacy against various genotypes (H1a, B3, D8). Results: The rSchwarz/FH(H1a) vaccine candidate demonstrated enhanced immunogenicity, with robust immune responses observed against the targeted genotypes. Additionally, it showed excellent genetic stability and safety profiles, indicating potential for effective use in vaccination programs. Notably, the vaccine provided cross-protection against multiple epidemic genotypes, highlighting its broader application in controlling measles outbreaks. Conclusions: Our findings suggest that the rSchwarz/FH(H1a) vaccine candidate represents a promising advancement in measles vaccine development. It has the potential to strengthen current measles vaccination strategies by providing improved immunogenicity and broader protection against different circulating genotypes. Further clinical trials are warranted to confirm these promising preclinical results. Full article

(This article belongs to the Special Issue Vaccines and Vaccine Preventable Diseases)

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11 pages, 360 KiB

Open AccessArticle

Two Outbreaks of Invasive Pneumococcal Disease in Nursing Homes in Gipuzkoa, Northern Spain

by José María Marimón, Ayla Manzanal, Olatz Mokoroa, Lorea Alvarez, Maite Rekalde and Diego Vicente

Vaccines 2025, 13(6), 570; https://doi.org/10.3390/vaccines13060570 (registering DOI) - 26 May 2025

Abstract

Background: The aging of the population has increased the number of frail people living in long-term care facilities, underscoring the need for continuous updates in infectious diseases prevention strategies. The aim of this study was to analyze two pneumococcal disease outbreaks in [...] Read more.

Background: The aging of the population has increased the number of frail people living in long-term care facilities, underscoring the need for continuous updates in infectious diseases prevention strategies. The aim of this study was to analyze two pneumococcal disease outbreaks in elderly residences in Gipuzkoa, northern Spain, their impact on residents, and the containment measures implemented. Material and methods: The outbreaks took place in 2023 and in 2024 in two residences of 111 and of 155 residents, respectively. Diagnosis was based on clinical criteria, radiological findings, and microbiological techniques. Pneumococcal isolates were characterized by whole-genome sequencing. Results: The outbreaks involved five and six residents, respectively. Most residents in both facilities had been vaccinated with the pneumococcal polysaccharide 23-valent vaccine (PPV23) more than five years prior. The median attack rates were 4.5% and 3.9%, lower than those reported in similar outbreaks. The adopted infection transmission prevention measures successfully limited the spread of the outbreaks. Conclusions: PPV23 vaccination did not prevent invasive pneumococcal infection in the affected residents. The vaccination of elderly people living in long-term care facilities with 20-valent and 21-valent pneumococcal conjugated vaccines should be evaluated as a new preventive measure. Full article

(This article belongs to the Section Epidemiology)

28 pages, 895 KiB

Open AccessReview

Vaccine Development for Human Pneumoviruses

by Elhadji Birane Mboup, Marie-Ève Hamelin, Julia Dubois, Manuel Rosa-Calatrava and Guy Boivin

Vaccines 2025, 13(6), 569; https://doi.org/10.3390/vaccines13060569 (registering DOI) - 26 May 2025

Abstract

Background: Pneumoviruses are etiologic agents of respiratory tract infections and a major cause of morbidity and mortality worldwide, particularly affecting young children, the elderly, and individuals with underlying clinical conditions. These viruses are associated with a significant burden, particularly in low- and middle-income [...] Read more.

Background: Pneumoviruses are etiologic agents of respiratory tract infections and a major cause of morbidity and mortality worldwide, particularly affecting young children, the elderly, and individuals with underlying clinical conditions. These viruses are associated with a significant burden, particularly in low- and middle-income countries, where reported deaths attributable to respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) in young children are important. Recent developments have been noted in the prevention of pneumoviral infections. Method: In this review, we analyzed clinical trials of the approved RSV vaccines, as well as the recent prominent platform technologies used in RSV vaccine research. In addition, we discussed combination vaccines targeting RSV, HMPV, and Human Parainfluenza Virus Type 3 (HPIV3) that have entered clinical trials. Results: Recent advancements include the approval of three RSV vaccine candidates: AREXVY^®(GSK), ABRYSVO^®(Pfizer), and mRESVIA^®(Moderna). These vaccines are primarily intended for older adults, with ABRYSVO^® also capable of providing passive immunization to infants via maternal administration. The review highlights RSV vaccine platform technologies and combination vaccines currently being evaluated in clinical settings. Conclusion: While significant progress has been made in RSV vaccine development, especially with three approved candidates, the development of vaccines for HMPV remains an unmet medical need. Ongoing research in combination vaccines holds promise for broader protection against multiple respiratory viruses in the future. Full article

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

17 pages, 2221 KiB

Open AccessArticle

Nanoparticle-Based mRNA Vaccine Induces Protective Neutralizing Antibodies Against Infectious Bronchitis Virus in In-Vivo Infection

by Aseno Sakhrie, Ankarao Kalluri, Zeinab H. Helal, Challa V. Kumar and Mazhar I. Khan

Vaccines 2025, 13(6), 568; https://doi.org/10.3390/vaccines13060568 (registering DOI) - 26 May 2025

Abstract

Background: Live attenuated and inactivated virus vaccines are commonly used against infectious bronchitis virus (IBV) in chickens, but they have limitations such as mutation risks and short efficacy. This study explores cationic bovine serum albumin (BSA) polyamine nanoparticles (NPs) for delivering IBV spike [...] Read more.

Background: Live attenuated and inactivated virus vaccines are commonly used against infectious bronchitis virus (IBV) in chickens, but they have limitations such as mutation risks and short efficacy. This study explores cationic bovine serum albumin (BSA) polyamine nanoparticles (NPs) for delivering IBV spike protein mRNA, aiming to develop a safer and more effective vaccine. Methods: A BSA-based nanoparticle system was designed with positive surface charges and characterized using dynamic light scattering (DLS), Zetasizer, and transmission electron microscopy (TEM). Its cytotoxicity, cellular uptake, and ability to deliver IBV spike protein mRNA were evaluated in macrophage-like chicken cell lines (HD11), followed by immunogenicity studies in SPF chickens to assess immune responses. Results: The study demonstrated successful binding and transfection efficiency of the in vitro transcription (IVT)-mRNA complexed with the NPs, which was enhanced with chloroquine. Immunogenicity studies in SPF chickens showed a significant increase in antibody titers in chickens vaccinated with the mRNA vaccine compared to the PBS control, indicating an effective immune response against the IBV S protein. Furthermore, the neutralization index doubled after a higher-dose mRNA booster with chloroquine, and PBMCs from immunized chickens exhibited a threefold higher stimulation index than the PBS control. Conclusions: BSA-based NPs effectively deliver IBV spike protein mRNA, enhancing immune responses and offering a promising strategy for a safer, more effective IBV vaccine. Full article

(This article belongs to the Special Issue Immune Strategies and Vaccine Development against Veterinary Virus Infection)

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35 pages, 5527 KiB

Open AccessArticle

FcRn-Driven Nanoengineered Mucosal Vaccine with Multi-Epitope Fusion Induces Robust Dual Immunity and Long-Term Protection Against Brucella

by Tingting Tian, Yuejie Zhu, Kaiyu Shang, Huidong Shi, Ruixue Xu, Mingzhe Li, Fuling Pu, Junyu Kuang, Jianbing Ding and Fengbo Zhang

Vaccines 2025, 13(6), 567; https://doi.org/10.3390/vaccines13060567 (registering DOI) - 26 May 2025

Abstract

Background: Brucellosis poses a significant public health challenge, necessitating effective vaccine development. Current vaccines have limitations such as safety concerns and inadequate mucosal immunity. This study aims to develop an FcRn-targeted mucosal Brucella vaccine by fusing the human Fc domain with Brucella’s [...] Read more.

Background: Brucellosis poses a significant public health challenge, necessitating effective vaccine development. Current vaccines have limitations such as safety concerns and inadequate mucosal immunity. This study aims to develop an FcRn-targeted mucosal Brucella vaccine by fusing the human Fc domain with Brucella’s multi-epitope protein (MEV), proposing a novel approach for human brucellosis prevention. Methods: The study developed a recombinant antigen (h-tFc-MEV) through computational analyses to validate antigenicity, structural stability, solubility, and allergenic potential. Molecular simulations confirmed FcRn binding. The vaccine was delivered orally via chitosan nanoparticles in murine models. Immunization was compared to MEV-only immunization. Post-challenge assessments were conducted to evaluate protection against Brucella colonization. Mechanistic studies investigated dendritic cell activation and antigen presentation. Results: Computational analyses showed that the antigen had favorable properties without allergenic potential. Molecular simulations demonstrated robust FcRn binding. In murine models, oral delivery elicited enhanced systemic immunity with elevated serum IgG titers and amplified CD4+/CD8+ T-cell ratios compared to MEV-only immunization. Mucosal immunity was evidenced by significant IgA upregulation across multiple tracts. Long-term immune memory persisted for six months. Post-challenge assessments revealed markedly reduced Brucella colonization in visceral organs. Mechanistic studies identified FcRn-mediated dendritic cell activation through enhanced MHC-II expression and antigen presentation efficiency. Conclusions: The FcRn-targeted strategy establishes concurrent mucosal and systemic protective immunity against Brucella infection. This novel vaccine candidate shows potential for effective human brucellosis prevention, offering a promising approach to address the limitations of current vaccines. Full article

(This article belongs to the Special Issue Animal Infectious Diseases and Vaccinology in One Health)

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17 pages, 1458 KiB

Open AccessArticle

Long-Term Immuno-Response and Risk of Breakthrough Infection After SARS-CoV-2 Vaccination in Kidney Transplantation

by Vincenzo Bellizzi, Mario Fordellone, Carmine Secondulfo, Paolo Chiodini and Giancarlo Bilancio

Vaccines 2025, 13(6), 566; https://doi.org/10.3390/vaccines13060566 (registering DOI) - 26 May 2025

Abstract

Background: Kidney transplant (KTx) recipients exhibit impaired responses to SARS-CoV-2 vaccination. Correlates of vaccine-induced immunity and risk factors for breakthrough infection are not fully defined. This study evaluated the humoral response trajectories and determinants of breakthrough infection in KTx recipients. Methods: [...] Read more.

Background: Kidney transplant (KTx) recipients exhibit impaired responses to SARS-CoV-2 vaccination. Correlates of vaccine-induced immunity and risk factors for breakthrough infection are not fully defined. This study evaluated the humoral response trajectories and determinants of breakthrough infection in KTx recipients. Methods: KTx recipients received two doses of the BNT162b2 mRNA vaccine three weeks apart and a booster after six months. Patients were categorized based on pre-vaccination status: previous COVID-19 disease (DIS), asymptomatic SARS-CoV-2 infection (INF), or infection-naïve (NEG). Serum anti-spike antibody titers were assessed at baseline, before the second dose, and at 1, 3, 6, 9, and 12 months. Linear mixed models and survival analyses were performed. Results: Of 326 enrolled patients, 189 with complete time-point data were included in the longitudinal analysis. Antibodies were detectable in 89% of DIS/INF at baseline and 91% before the second dose, but were negligible in NEG. In NEG, the seropositivity increased after vaccination and booster, reaching 78% at 12 months. Age (−5% per year, p < 0.001) and BMI (+10% per unit, p = 0.004) influenced titers; antimetabolites and steroids had strong negative effects (−70%, p = 0.005; −84%, p = 0.001). Breakthrough infections occurred in 104 (31.9%); 40% were asymptomatic, and 2 patients died. An mTOR inhibitor was associated with a reduced infection risk (OR 0.27 [CI: 0.09–0.70], p = 0.009). Higher antibody titers correlated with delayed infection (p = 0.063). Conclusions: In KTx patients, humoral response to SARS-CoV-2 vaccination is limited in infection-naïve patients but improved by booster dosing; the hybrid immunity is more effective. Immunosuppressive regimens influence the immune response, and mTOR inhibitors may protect against breakthrough infection. Full article

(This article belongs to the Special Issue COVID Vaccines: Design, Development, and Immune Response Studies: 2nd Edition)

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19 pages, 665 KiB

Open AccessArticle

Real-World Effectiveness of Boosting Against Omicron Hospitalization in Older Adults, Stratified by Frailty

by Liang En Wee, Enoch Xue Heng Loy, Jue Tao Lim, Wei Hao Kwok, Calvin Chiew, Christopher Lien, Barbara Helen Rosario, Ian Yi Onn Leong, Reshma Aziz Merchant, David Chien Boon Lye and Kelvin Bryan Tan

Vaccines 2025, 13(6), 565; https://doi.org/10.3390/vaccines13060565 (registering DOI) - 26 May 2025

Abstract

Background/Objectives: Older adults with frailty are at-risk of worse outcomes following respiratory-viral-infections such as COVID-19. Data on effectiveness of vaccination/boosting in frail older adults during Omicron is lacking. Methods: National healthcare-claims data and COVID-19 registries were utilized to enroll a cohort of older [...] Read more.

Background/Objectives: Older adults with frailty are at-risk of worse outcomes following respiratory-viral-infections such as COVID-19. Data on effectiveness of vaccination/boosting in frail older adults during Omicron is lacking. Methods: National healthcare-claims data and COVID-19 registries were utilized to enroll a cohort of older Singaporeans (≥60 years) as of 1 January 2022, divided into low/intermediate/high-risk for frailty; matching weights were utilized to adjust for sociodemographic differences/vaccination uptake at enrolment across frailty categories. Competing-risk-regression (Fine-Gray) taking death as a competing risk, with matching weights applied, was utilized to compare risks of COVID-19-related hospitalizations and severe COVID-19 across frailty levels (low/intermediate/high-risk), with estimates stratified by booster status. Individuals were followed up until study end-date (20 December 2023). Results: 874,160 older adults were included during Omicron-predominant transmission; ~10% had intermediate/high-frailty-risk. Risk of hospitalization/severe COVID-19 was elevated in those with intermediate/high-frailty-risk up to XBB/JN.1 transmission. Boosting was associated with decreased risk of COVID-19-related hospitalization across all frailty categories in infection-naïve individuals. However, in infection-naïve older adults with high-frailty-risk, while receipt of first boosters was associated with lower risk of COVID-19-hospitalization/severe COVID-19, additional booster doses did not reduce risk. In reinfected older adults, first boosters were still associated with lower hospitalization risk (adjusted-hazards-ratio, aHR = 0.55, 95% CI = 0.33–0.92) among the non-frail, but not in the intermediate/high-frailty-risk minority. Conclusions: First boosters were associated with reduced adverse COVID-19 outcomes across all frailty categories in infection-naïve older adults during Omicron. However, in the high-frailty minority, boosting did not additionally reduce risk in reinfected individuals with hybrid immunity, and beyond the first booster for infection-naïve individuals. Full article

(This article belongs to the Special Issue COVID Vaccines: Design, Development, and Immune Response Studies: 2nd Edition)

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15 pages, 612 KiB

Open AccessArticle

Rates of SARS-CoV-2 Breakthrough Infection or Severe COVID-19 and Associated Risk Factors After Primary and Booster Vaccination Against COVID-19 in the Netherlands

by Jesse M. van den Berg, Marieke T. Blom, Jetty A. Overbeek, Sharon Remmelzwaal, Ron M. C. Herings and Petra J. M. Elders

Vaccines 2025, 13(6), 564; https://doi.org/10.3390/vaccines13060564 - 26 May 2025

Abstract

Background: The effectiveness of COVID-19 vaccines appears to decline rapidly over time due to waning immunity and immune evasion by emerging variants of concern, and may be reduced in high-risk populations. We aimed to evaluate the rates of SARS-CoV-2 breakthrough infection or severe [...] Read more.

Background: The effectiveness of COVID-19 vaccines appears to decline rapidly over time due to waning immunity and immune evasion by emerging variants of concern, and may be reduced in high-risk populations. We aimed to evaluate the rates of SARS-CoV-2 breakthrough infection or severe COVID-19, both in individuals who had completed their primary COVID-19 vaccination, and in those who had received their first booster vaccination. Specifically, we aimed to evaluate whether persons with certain risk factors, such as age, gender, socioeconomic status (SES), and specified comorbidities have an increased risk of either breakthrough infection or severe COVID-19, compared to those without the respective risk factors. Methods: Data on COVID-19 vaccinations, infections, hospitalizations, and deaths were collected from the PHARMO Data Network, consisting of health records from Dutch residents. Two cohorts were established: (1) all persons who have completed their primary COVID-19 vaccination regimen, and (2) those who have received their first booster vaccination. The outcomes were SARS-CoV-2 breakthrough infection, and severe COVID-19, defined as either hospitalization or death following SARS-CoV-2 infection. Incidence rates of these outcomes were calculated in both cohorts. The adjusted incidence rate ratios of these outcomes in persons with certain risk factors were calculated, using generalized linear models with a Poisson distribution. Results: In 2021, a total of 1,090,567 individuals received either two doses of BNT162b2, AZD1222, or mRNA-1273, or one dose of Ad26.COV2.S and were included in the primary vaccination cohort, of which 344,153 (31.6%) received a booster vaccination. Overall incidence rates of SARS-CoV-2 breakthrough infection and severe COVID-19 after primary vaccination were 29.9 and 3.1 per 1000 person-years, respectively, and after booster vaccination were 256.4 and 2.3, respectively. Male gender, older age, lower SES, history of COVID-19, and recent hospitalization were factors associated with a lower risk of breakthrough infection after primary vaccination, and a higher risk of severe COVID-19. The risk of severe COVID-19 after primary vaccination was increased in persons with several comorbidities, compared to those without, and remained elevated after booster vaccination in persons with diabetes or lung disease. Conclusions: Our study emphasizes the crucial role of boosters in reducing breakthrough infections, particularly in high-risk populations. The varied impact on severe outcomes in individuals with comorbidities underscores the need for ongoing surveillance and tailored vaccination strategies. Full article

(This article belongs to the Special Issue COVID Vaccines: Design, Development, and Immune Response Studies: 2nd Edition)

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28 pages, 2042 KiB

Open AccessReview

Rational Design and Immunological Mechanisms of Circular RNA-Based Vaccines: Emerging Frontiers in Combating Pathogen Infection

by Ying Zhang, Shumei Jin, Zan Zuo, Shujing Liu, Juan Xu, Chongyi Yang, Ping Wan, Linting Xun, Mei Luo, Fan Yang, Wenjie Chen, Zhengji Song and Jialong Qi

Vaccines 2025, 13(6), 563; https://doi.org/10.3390/vaccines13060563 - 26 May 2025

Abstract

Vaccines remain one of the most effective tools in combating infectious diseases, though traditional platforms are constrained by limitations including suboptimal immunogenicity, safety concerns, and manufacturing complexity. Circular RNA (circRNA) vaccines have recently emerged as a novel vaccine modality, demonstrating unique advantages including [...] Read more.

Vaccines remain one of the most effective tools in combating infectious diseases, though traditional platforms are constrained by limitations including suboptimal immunogenicity, safety concerns, and manufacturing complexity. Circular RNA (circRNA) vaccines have recently emerged as a novel vaccine modality, demonstrating unique advantages including high stability, low innate immunogenicity, and sustained antigen expression. Although early research has predominantly focused on viral targets, accumulating evidence now supports the application potential of circRNA vaccines against diverse pathogens, particularly antibiotic-resistant bacteria. Through encoding critical antigens or virulence factors, these circRNA vaccines demonstrate capability to induce protective immune responses, presenting a viable alternative to conventional antimicrobial strategies. This review highlights recent advances in circRNA vaccine development, spanning synthetic circularization techniques, delivery approaches, and immunological mechanisms. We emphasize their potential against viral, bacterial, fungal, and parasitic infections, while addressing current challenges and future research directions of this emerging platform. Collectively, these insights underscore circRNA’s multifaceted versatility and its expanding relevance in next-generation vaccine innovation. Full article

(This article belongs to the Special Issue Next-Generation Vaccine and Immunotherapy)

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10 pages, 230 KiB

Open AccessArticle

Persistence of Anti-HB Antibodies in Healthcare Trainees: The Impact of Childhood Versus Adolescent Vaccination

by Luca Di Giampaolo, Luca Coppeta, Paola Borrelli, Piergiorgio Astolfi, Andrea Resta, Lucia Loffredo, Flavia Di Menno Di Bucchianico, Rocco Mangifesta, Lorenzo Ippoliti and Cristiana Ferrari

Vaccines 2025, 13(6), 562; https://doi.org/10.3390/vaccines13060562 - 26 May 2025

Abstract

Background: Hepatitis B virus (HBV) infection remains a significant occupational health concern for healthcare workers (HCWs), including trainees exposed to biological risks. Although vaccination is the most effective preventive measure, the persistence of immunity over time and the need for booster doses remain [...] Read more.

Background: Hepatitis B virus (HBV) infection remains a significant occupational health concern for healthcare workers (HCWs), including trainees exposed to biological risks. Although vaccination is the most effective preventive measure, the persistence of immunity over time and the need for booster doses remain subjects of debate. Objective: The present study aims to assess the prevalence of protective anti-HB antibody titers among healthcare trainees at the “SS Annunziata” Hospital in Chieti, comparing those vaccinated in infancy with those vaccinated during adolescence. Methods: A retrospective observational study was conducted on 2028 healthcare trainees from 2021 to 2024. Participants were divided into two groups based on vaccination timing: infancy (PED group) and adolescence (ADO group). Serological tests were performed to measure anti-HB titers, with a protective threshold set at ≥10 IU/L. Statistical analyses were conducted to evaluate differences in immunity persistence between the two groups. The results showed that the overall prevalence of protective anti-HB titers was 50.7%, with significant differences between the PED and ADO groups. Protective immunity was observed in 79.2% of individuals vaccinated during adolescence, compared to 44.6% of those vaccinated in infancy (p < 0.001). No significant differences in antibody persistence were found between males and females. Notably, 92.4% of participants with non-protective titers received a booster dose within two months of testing. Conclusions: The study confirms a significant decline in anti-HB titers over time among individuals vaccinated in infancy, suggesting a potential need for booster doses later in adulthood. The high adherence to vaccination recommendations among healthcare trainees is a promising finding, reinforcing the importance of continuous education and immunization programmes in healthcare settings. Further research, including longitudinal studies and additional HBV biomarkers, is necessary to optimize vaccination strategies and long-term immunity monitoring in HCWs. Full article

23 pages, 2542 KiB

Open AccessArticle

HPV Infection Prevalence, Vaccination-Related Knowledge, Attitudes, and Barriers Among Women Aged 30–64 in Shenzhen, China: A Cross-Sectional Study

by Zhongai Ouyang, Minting Zhu, Zhijian Chen, Weigui Ni, Lijuan Lai, Bingyi Lin, Long Jiang, Yi Jing and Jingjie Fan

Vaccines 2025, 13(6), 561; https://doi.org/10.3390/vaccines13060561 - 25 May 2025

Abstract

Background: the distribution of human papillomavirus (HPV) infection, vaccination rates, and awareness levels varies across China. Methods: this study examined HPV infection prevalence, vaccine uptake, and barriers among 2440 women aged 30–64 in Shenzhen, China, using partial least squares structural equation [...] Read more.

Background: the distribution of human papillomavirus (HPV) infection, vaccination rates, and awareness levels varies across China. Methods: this study examined HPV infection prevalence, vaccine uptake, and barriers among 2440 women aged 30–64 in Shenzhen, China, using partial least squares structural equation modeling (PLS-SEM) to analyze associated factors. Results: The overall HPV prevalence was 14.2% (347/2440), with HPV52 being the most common type, followed by HPV58 and HPV53. Factors significantly associated with HPV infection included more sexual partners, genital tract infections, manual labor, and single marital status (p < 0.05), whereas higher education demonstrated a protective association (p < 0.05). The HPV vaccination rate was 41.8% in ages 30–45. There were direct effect indicators of younger age, fewer pregnancies, and premenopausal status (p < 0.05) on HPV vaccine uptake, whereas inversely associated factors included divorce/widowed, lower household income, irregular menstruation, more deliveries, no contraception, and lack of HPV knowledge. Among 828 unvaccinated individuals, 47.9% of those aged 46–64 were willing if the age restrictions were expanded, with the main barrier being a lack of vaccine knowledge (40.7%). Willingness was significantly associated with younger age and healthcare occupation (p < 0.05), but negatively with eastern Shenzhen residence, lower household income, no HPV disease awareness, abnormal leucorrhea, lack of HPV knowledge, and belief against post-vaccination screening (p < 0.05). Conclusions: Socioeconomic disparities in HPV infection and vaccination rates in Shenzhen highlight intervention priorities. The impact of HPV knowledge underscores the need for effective health communication. The vaccination willingness and infection status among women aged 45+ provide supporting evidence for expanding HPV vaccination to older age groups. Full article

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

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16 pages, 7103 KiB

Open AccessArticle

Adjuvanted RNA Origami—A Tunable Peptide Assembly Platform for Constructing Cancer Nanovaccines

by Theresa Yip, Xinyi Tu, Xiaodong Qi, Hao Yan and Yung Chang

Vaccines 2025, 13(6), 560; https://doi.org/10.3390/vaccines13060560 - 25 May 2025

Abstract

Background/Objectives: Cancer peptide vaccines represent a promising strategy to develop targeted and personalized treatments for cancer patients. While tumor peptides alone are insufficient in mounting effective immune responses, the addition of adjuvants can enhance their immunogenicity. Nanoparticle delivery systems have been explored as [...] Read more.

Background/Objectives: Cancer peptide vaccines represent a promising strategy to develop targeted and personalized treatments for cancer patients. While tumor peptides alone are insufficient in mounting effective immune responses, the addition of adjuvants can enhance their immunogenicity. Nanoparticle delivery systems have been explored as vaccine carriers to incorporate both adjuvants and peptides. One such nanoparticle is RNA origami (RNA-OG), a nucleic acid nanostructure that is programmed to form different sizes and shapes. Our designed RNA-OG can incorporate various biomolecules and has intrinsic adjuvant activity by acting as a toll-like receptor 3 agonist. We previously showed that the RNA-OG functions as an adjuvanted, carrier-free vaccine platform to assemble peptides. Although effective, only a fixed number of peptides (13) could be covalently linked to each RNA-OG. Methods: Here, we developed a simple physical assembly strategy to attach polylysine-linked neopeptides onto RNA-OG so that the number of peptides per RNA-OG could be readily tuned and tested for their immunogenicity. Results: Although the vaccines with a high number of peptides, i.e., 100–200 peptides/RNA-OG, led to greater peptide presentation by bone marrow-derived dendritic cells, they failed to mount effective CD8⁺ T cell responses against engrafted tumor cells, probably owing to an induction of early T cell exhaustion. Interestingly, the same vaccine format with a low number of peptides, i.e., 10–15 peptides/RNA-OG, enhanced CD8⁺ T cell responses without provoking T cell exhaustion in tumor-bearing mice, leading to strong protective anti-tumor immunity. In comparison, the covalently assembled RNA-OG-peptide vaccine, having a similarly low peptide dosage, offered the highest therapeutic efficacy. Thus, our RNA-OG nanostructure provides a simple and tunable platform for peptide loading to optimize vaccine efficacy. Conclusions: Our findings have significant implications for peptide vaccine design regarding peptide dosages and structural stability of RNA-OG complexed with peptides, which could guide the development of more effective peptide vaccines for cancer immunotherapy. Full article

(This article belongs to the Special Issue Novel Immunotherapies, Cell Therapies and Cancer Vaccines)

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22 pages, 5356 KiB

Open AccessArticle

Mucosal and Serum Neutralization Immune Responses Elicited by COVID-19 mRNA Vaccination in Vaccinated and Breakthrough-Infection Individuals: A Longitudinal Study from Louisville Cohort

by Lalit Batra, Divyasha Saxena, Triparna Poddar, Maryam Zahin, Alok Amraotkar, Megan M. Bezold, Kathleen T. Kitterman, Kailyn A. Deitz, Amanda B. Lasnik, Rachel J. Keith, Aruni Bhatnagar, Maiying Kong, Jon D. Gabbard, William E. Severson and Kenneth E. Palmer

Vaccines 2025, 13(6), 559; https://doi.org/10.3390/vaccines13060559 - 24 May 2025

Abstract

Background/Objectives: The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2), has resulted in 777 million cases worldwide. Various vaccines have been approved to control the spread of COVID-19, with mRNA vaccines (Pfizer and Moderna) being widely used in the [...] Read more.

Background/Objectives: The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2), has resulted in 777 million cases worldwide. Various vaccines have been approved to control the spread of COVID-19, with mRNA vaccines (Pfizer and Moderna) being widely used in the USA. We conducted a prospective longitudinal study to analyze the immune response elicited by two/three and four doses of monovalent mRNA vaccines in both vaccinated individuals and those who experienced breakthrough infections. Participants were stratified into different age groups: 18–40, 41–60, and over 60 years. Methods: We assessed cross-variant neutralization responses in two cohorts—Cohort I: n = 167 (serum), Cohort II: n = 92 (serum and nasal swab) samples—using infectious virus microneutralization assay (MN) and antibody (IgG or IgA) binding ELISA titers to the spike protein receptor binding domain (RBD). Samples were collected from the Louisville Metro–Jefferson County Co-Immunity Project, a federally funded, population-based study for the surveillance of SARS-CoV-2 in Jefferson County, Kentucky during 2020–2022, involving both health care workers and a local community. Results: Individuals who received two doses of the mRNA vaccine exhibited reduced neutralization against Beta, Delta, and Omicron BA.1 variants compared to wildtype Wuhan, with further decline observed six months post-booster vaccination. However, individuals who experienced natural COVID-19 infection (breakthrough) after receiving two vaccine doses showed enhanced neutralization and antibody responses, particularly against Omicron BA.1. Following the 3rd dose, antibodies and neutralization responses were restored. Among triple-vaccinated individuals, reduced neutralization was observed against Omicron variants BA.1, BA.5, and BA.2 compared to Wuhan. Neutralization responses were better against BA.2 variant compared to BA.1 and BA.5. However, individuals who received three doses of vaccine and experienced a breakthrough infection (n = 45) elicited significantly higher neutralizing antibodies responses against all Omicron subvariants compared to vaccinated individuals. Interestingly, nasal swab samples collected from volunteers with breakthrough infection showed significantly elevated spike-reactive mucosal IgA antibodies and enhanced cross neutralization against BA.1, BA.2, and BA.5 compared to individuals who received only three vaccine doses. Conclusions: mRNA vaccination elicits a strong systemic immune response by boosting serum neutralizing antibodies (NAb), although this protection wanes over time, allowing new variants to escape neutralization. Breakthrough individuals have extra enrichment in nasal NAb offering protection against emerging variants. This longitudinal immune profiling underscores the strengthening of pandemic preparedness and supports the development of durable mucosal vaccines against respiratory infectious disease. 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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15 pages, 1707 KiB

Open AccessArticle

Safety and Immunogenicity of OVX836, a Nucleoprotein-Based Universal Influenza Vaccine, Co-Administered with Fluarix^® Tetra, a Seasonal Hemagglutinin-Based Vaccine

by Nicola Groth, Jacques Bruhwyler, Jessika Tourneur, Emilie Piat, Philippe Moris, Alexandre Le Vert and Florence Nicolas

Vaccines 2025, 13(6), 558; https://doi.org/10.3390/vaccines13060558 (registering DOI) - 23 May 2025

Abstract

Background/Objectives: The combination of a hemagglutinin antigen (HA)-based inactivated influenza vaccine (IIV; Fluarix^® Tetra; GlaxoSmithKline) with a nucleoprotein (NP)-based vaccine, such as OVX836, should increase the efficacy of influenza vaccines since it leverages two complementary immunological mechanisms: HA antibodies targeting the [...] Read more.

Background/Objectives: The combination of a hemagglutinin antigen (HA)-based inactivated influenza vaccine (IIV; Fluarix^® Tetra; GlaxoSmithKline) with a nucleoprotein (NP)-based vaccine, such as OVX836, should increase the efficacy of influenza vaccines since it leverages two complementary immunological mechanisms: HA antibodies targeting the virus envelope and neutralizing it, and an NP cell-mediated immune (CMI) response destroying infected cells. Methods: This was a randomized, double-blind, Phase 2a study (ClinicalTrials.gov NCT05284799) including three groups of 60 healthy subjects (18–55 years old) receiving either IIV + placebo, IIV + OVX836 (480 µg), or OVX836 + placebo intramuscularly and concomitantly into the same deltoid muscle. The endpoints were reactogenicity, safety, and immunogenicity (hemagglutination inhibition assay [HAI], anti-NP immunoglobulin G [IgG], and NP-specific cell-mediated immunity [CMI]). Results: The co-administration of IIV + OVX836 was safe and well-tolerated. The HAI response was strong and similar in the two IIV groups with no interference of OVX836. The humoral anti-NP IgG and NP-specific CMI responses to OVX836 were strong in the two OVX836 groups, and no major interference of IIV was observed. Conclusions: This study supports further clinical development of OVX836 as a combined IIV/OVX836 seasonal vaccine capable of inducing robust and complementary HAI and CMI NP-specific responses. Full article

(This article belongs to the Section Influenza Virus Vaccines)

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15 pages, 348 KiB

Open AccessReview

Maternal Vaccination as an Integral Part of Life-Course Immunization: A Scoping Review of Uptake, Barriers, Facilitators, and Vaccine Hesitancy for Antenatal Vaccination in Ireland

by Adeyinka Sanni, Nuha Ibrahim, Dorothea Tilley, Sandra Bontha, Amy McMorrow and Roy K. Philip

Vaccines 2025, 13(6), 557; https://doi.org/10.3390/vaccines13060557 - 23 May 2025

Abstract

Background: Maternal vaccination is a critical primary preventive approach and an integral part of life-course immunization strategy, influencing the infection-associated morbidity and mortality in pregnant women, foetuses, and young infants. Despite clear guidelines for the administration of vaccines against tetanus, diphtheria, pertussis [...] Read more.

Background: Maternal vaccination is a critical primary preventive approach and an integral part of life-course immunization strategy, influencing the infection-associated morbidity and mortality in pregnant women, foetuses, and young infants. Despite clear guidelines for the administration of vaccines against tetanus, diphtheria, pertussis (Tdap), influenza, and COVID-19 during pregnancy, maternal vaccination rates remain suboptimal in Ireland as per the National Immunisation Office of the Health Service Executive (HSE). Aim: This review explores the prevailing status, uptake factors, and maternal immunization-specific vaccine hesitancy in Ireland. Method: A scoping review was conducted, searching nine electronic databases, including the Irish health research repository Lenus. The search strategy utilised a Population–Concept–Context framework (pregnant women—vaccine uptake/hesitancy—Ireland). Key factors identified and categorised according to the 5A framework: access, affordability, awareness, acceptance, and activation. Results: Searches yielded 2457 articles, and 12 eligible studies were included for review. Influencing factors were identified in each of the 5A dimensions, with the majority relating to acceptance and awareness. Positively associated factors included healthcare provider (HCP) recommendation and knowledge of vaccine safety. Potential antenatal barriers were maternal lack of knowledge of vaccine-preventable illness severity, infection risks, and vaccine safety concerns. A pregnant woman’s primary motivation for antenatal immunization was protection of her infant; however, the reluctance of HCPs to prescribe all recommended antenatal vaccines, inadequate immunization-specific discussion during antenatal consultations, and suboptimal knowledge of pregnancy-specific vaccine safety hampered potential positive influences. The Irish national immunization policy was a facilitator of affordability. Activation can be achieved through public health awareness campaigns and interdisciplinary promotion of maternal vaccination uptake. Conclusions: Maternal vaccination uptake in Ireland remains suboptimal, and a coordinated, targeted approach updating HCP recommendations, enhancing maternal awareness, and highlighting vaccine safety in pregnancy would be required to meet the life-course immunization goals recommended by WHO. By adopting a life-course immunization approach for healthy living, with maternal vaccination as the pivotal central point, vaccination programmes could close immunity gaps at various life stages. Full article

(This article belongs to the Section Clinical Immunology)

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Graphical abstract

30 pages, 3281 KiB

Open AccessReview

The Bioengineering of Insect Cell Lines for Biotherapeutics and Vaccine Production: An Updated Review

by Michał Sułek and Agnieszka Szuster-Ciesielska

Vaccines 2025, 13(6), 556; https://doi.org/10.3390/vaccines13060556 - 23 May 2025

Abstract

Insect cell lines are a cornerstone of recombinant protein production, providing a versatile platform for biopharmaceutical and research applications. In the early 20th century, scientists first attempted to culture insect cells in vitro, developing continuous cell lines to produce the first insect cell-derived [...] Read more.

Insect cell lines are a cornerstone of recombinant protein production, providing a versatile platform for biopharmaceutical and research applications. In the early 20th century, scientists first attempted to culture insect cells in vitro, developing continuous cell lines to produce the first insect cell-derived recombinant protein, IFN-β. Initial successes, along with advancements in the use of insect cells for recombinant protein manufacturing, primarily relied on baculovirus expression vector systems (BEVSs), which enable heterologous gene expression in infected cells. Today, growing attention is focused on baculovirus-free systems based on the transfection of insect cells with plasmid DNA. This approach simplifies the final product purification process and facilitates the development of stable monoclonal cell lines that produce recombinant proteins or protein complexes, particularly virus-like particles (VLPs). Thanks to advancements in genetic engineering and the application of adaptive laboratory evolution (ALE) methods, significant strides have been made in overcoming many limitations associated with insect cell BEVSs, ultimately enhancing the reliability, yield, and quality of the biomanufacturing process. Our manuscript discusses the history of developing insect cell lines, presents various recombinant protein production systems utilizing these cells, and summarizes modifications aimed at improving insect cell lines for recombinant protein biomanufacturing. Finally, we explore their implications in pharmaceutical production, particularly on Nuvaxovid^®/Covovax, which is the latest approved vaccine developed using insect cell BEVSs for protection against SARS-CoV-2. Full article

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14 pages, 1907 KiB

Open AccessArticle

Comparative Analysis of Long-Term Measles Immune Response After Natural Infection and Routine Vaccination in China

by Sihong Zhao, Qianli Wang, Juan Yang, Qiaohong Liao, Juanjuan Zhang, Xiaoyu Zhou, Jiaxin Zhou, Zeyao Zhao, Yuxia Liang, Junteng Luo, Jingting Cai, Yanpeng Wu, Wei Wang and Hongjie Yu

Vaccines 2025, 13(6), 555; https://doi.org/10.3390/vaccines13060555 - 23 May 2025

Abstract

Background: Given the significant impact of population immunity on the measles epidemic, understanding immunity differences among populations with varying immunity backgrounds is necessary for identifying immunity gaps and informing vaccination policies. In this study, we aimed to determine the distinct dynamics of vaccine-induced [...] Read more.

Background: Given the significant impact of population immunity on the measles epidemic, understanding immunity differences among populations with varying immunity backgrounds is necessary for identifying immunity gaps and informing vaccination policies. In this study, we aimed to determine the distinct dynamics of vaccine-induced and naturally acquired antibodies, with specific focus on difference in vaccine-induced antibody responses across different birth cohorts. Methods: Based on two cohorts and one cross-sectional study conducted in Anhua County, Hunan Province, China, serum samples from children who followed China’s routine measles vaccination schedule (i.e., two-dose schedule at 8/18 months) and adults who acquired immunity through natural infection were tested for measles IgG antibodies using an enzyme-linked immunosorbent assay. The generalized additive mixed model and a mechanistic model were employed to describe antibody dynamics following vaccination and infections. Wavelet analysis was used to investigate the temporal relationship between the measles epidemic and long-term antibody levels after natural infection. Results: A total of 408 children (0–12 years) and 222 adults (54–84 years) were included in the present study. Vaccine-induced antibody levels following 8 m/18 m vaccination were estimated to fall below the protective threshold of 200 mIU/mL by age of 15.8, whereas antibody levels following infections remained high. The decay rate of vaccine-induced antibodies was estimated at 3.0 × 10⁻³ log-log mIU/mL per year, whereas naturally acquired measles antibodies persisted lifelong with a significantly lower decay rate of 2.30 × 10⁻⁵ log-log mIU/mL per year. Moreover, vaccine-induced antibody levels in children born after 2010—a period of low measles incidence—declined more rapidly (duration of protective immunity: 12.5 years), compared to those born before 2010. Discussion: Our findings revealed immunity heterogeneity among individuals with difference measles immunity backgrounds. In particular, the birth-cohort specific differences in vaccine-induced immunity highlighted the key role of young generations born in settings with low measles incidence in contributing to population immunity gaps. This underlines that greater attention should be given to this group in future catch-up vaccination efforts. Full article

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

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22 pages, 1468 KiB

Open AccessReview

The Impact of COVID-19 and the Practical Importance of Vaccinations and Nirmatrelvir/Ritonavir for Patients with Cardiovascular Disease

by Marcin Wełnicki, Artur Mamcarz, Ernest Kuchar, Przemysław Mitkowski, Jerzy Jaroszewicz, Krzysztof Tomasiewicz, Mariusz Gąsior, Przemysław Leszek, Karol Adam Kamiński and Jacek Wysocki

Vaccines 2025, 13(6), 554; https://doi.org/10.3390/vaccines13060554 - 23 May 2025

Abstract

The COVID-19 pandemic posed a huge challenge to global health systems. In addition to searching for effective methods of treating and preventing infection with a new pathogen, we could once again observe that severe respiratory infection and its complications can be become a [...] Read more.

The COVID-19 pandemic posed a huge challenge to global health systems. In addition to searching for effective methods of treating and preventing infection with a new pathogen, we could once again observe that severe respiratory infection and its complications can be become a challenging problem for cardiac patients. Empirical observations are fully confirmed by the results of clinical trials. Patients with risk factors and already diagnosed with cardiovascular diseases are particularly exposed to the severe course of COVID-19, including death. That is why we consider it so important to promote vaccinations against COVID-19 as a safe and effective method of preventing serious infections in this special group of patients, in accordance with the updated recommendations of relevant experts. If an infection is detected, depending on its form and the risk of hospitalization, there are also several antiviral treatment strategies. Nirmatrelvir/ritonavir therapy is particularly effective in selected patient groups, but its use requires analysis of the cardiac pharmacotherapy regimen in the context of potentially significant drug interactions. Full article

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

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