Vaccines

15 pages, 678 KB

Open AccessArticle

Local Health Department COVID-19 Vaccination Efforts and Associated Outcomes: Evidence from Jefferson County, Kentucky

by Shaminul H. Shakib, Seyed M. Karimi, J. Daniel McGeeney, Md Yasin Ali Parh, Hamid Zarei, Yuting Chen, Ben Goldman, Dana Novario, Michael Schurfranz, Ciara A. Warren, Demetra Antimisiaris, Bert B. Little, W. Paul McKinney and Angela J. Graham

Vaccines 2025, 13(9), 901; https://doi.org/10.3390/vaccines13090901 (registering DOI) - 26 Aug 2025

Abstract

Background: While disparities in vaccine uptake have been well documented, few studies have evaluated the impact of local vaccine programs on COVID-19 outcomes, namely cases, hospitalizations, and deaths. Objectives: Evaluate the impact of COVID-19 vaccine doses coordinated by the Louisville Metro [...] Read more.

Background: While disparities in vaccine uptake have been well documented, few studies have evaluated the impact of local vaccine programs on COVID-19 outcomes, namely cases, hospitalizations, and deaths. Objectives: Evaluate the impact of COVID-19 vaccine doses coordinated by the Louisville Metro Department of Public Health and Wellness (LMPHW) on COVID-19 outcomes by race across ZIP codes from December 2020 to May 2022 in Jefferson County, Kentucky. Methods: Fixed-effects longitudinal models with ZIP codes as ecological time-series units were estimated to measure the association between COVID-19 vaccine doses and outcomes with time lags of one week, two weeks, three weeks, four weeks, and one month. Models were adjusted for time (week or month of the year) and its interaction with ZIP code. Results: In the one-week lag model, significant negative associations were observed between LMPHW-coordinated vaccine doses and COVID-19 outcomes, indicating reductions of 11.6 cases, 0.4 hospitalizations, and 0.3 deaths per 100 doses administered. Vaccine doses were consistently associated with fewer deaths among White residents across all lags, with an average reduction of 0.2 deaths per 100 doses. No significant associations were found for Black residents. Temporal trends also indicated declines in COVID-19 outcomes when LMPHW’s vaccine administration program peaked, between March and May 2021. Conclusions: Timely uptake of COVID-19 vaccines remains critical in avoiding severe outcomes, especially with emerging variants. Racial disparities in vaccine–outcome associations emphasize the potential need for equitable, community-driven vaccine campaigns to improve population health outcomes. Full article

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

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21 pages, 854 KB

Open AccessReview

Nanovaccines: Innovative Advances from Design Strategies to Clinical Translation

by Jiuxiang He, Wen Xiao, Dong Hua, Minchi Liu, Hongxia Guo, Li Xu, Meiling Xiao, Yunsha Du and Jintao Li

Vaccines 2025, 13(9), 900; https://doi.org/10.3390/vaccines13090900 (registering DOI) - 25 Aug 2025

Abstract

Nanovaccines have emerged as a transformative platform in immunotherapy, distinguished by their capabilities in targeted antigen delivery, enhanced immunogenicity, and multifunctional integration. By leveraging nanocarriers, these vaccines achieve precise antigen transport, improve immune activation efficiency, and enable synergistic functions such as antigen protection [...] Read more.

Nanovaccines have emerged as a transformative platform in immunotherapy, distinguished by their capabilities in targeted antigen delivery, enhanced immunogenicity, and multifunctional integration. By leveraging nanocarriers, these vaccines achieve precise antigen transport, improve immune activation efficiency, and enable synergistic functions such as antigen protection and adjuvant co-delivery. This review comprehensively explores the foundational design principles of nanovaccines, delves into the diversity of nanovaccine design strategies—including the selection of primary carrier materials, functionalization modification, synergistic delivery of immune adjuvants, and self-assembled nano-delivery systems—and highlights their applications in cancer immunotherapy, infectious disease and autoimmune diseases. Furthermore, it critically examines existing technical challenges and translational barriers, providing an integrative reference to guide future research and development in this dynamic field. Full article

(This article belongs to the Section Vaccine Design, Development, and Delivery)

19 pages, 1823 KB

Open AccessReview

mRNA and DNA-Based Vaccines in Genitourinary Cancers: A New Frontier in Personalized Immunotherapy

by Jasmine Vohra, Gabriela Rodrigues Barbosa and Leonardo O. Reis

Vaccines 2025, 13(9), 899; https://doi.org/10.3390/vaccines13090899 (registering DOI) - 25 Aug 2025

Abstract

Genitourinary (GU) cancers, including prostate, bladder, and renal cancers, represent a significant burden on global health. Conventional treatments, while effective in certain contexts, face limitations due to tumor heterogeneity, therapeutic resistance, and relapse. Recent advances in cancer immunotherapy, particularly in the development of [...] Read more.

Genitourinary (GU) cancers, including prostate, bladder, and renal cancers, represent a significant burden on global health. Conventional treatments, while effective in certain contexts, face limitations due to tumor heterogeneity, therapeutic resistance, and relapse. Recent advances in cancer immunotherapy, particularly in the development of personalized mRNA and DNA-based vaccines, have opened new avenues for precise and durable antitumor responses. These vaccines are being developed to leverage neoantigen identification and next-generation sequencing technologies, with the goal of tailoring immunotherapeutic interventions to individual tumor profiles. mRNA vaccines offer rapid, non-integrative, and scalable, with encouraging results reported in infectious diseases and early-phase cancer trials. DNA vaccines, known for their stability and ease of modification, show promise in generating robust cytotoxic T-cell responses. This review discusses the current landscape, preclinical findings, and ongoing clinical trials of mRNA and DNA-based vaccines in GU cancers, highlighting delivery technologies, combination strategies with immune checkpoint inhibitors, and future challenges, including tumor immune evasion and regulatory hurdles. Integrating immunogenomics and artificial intelligence into vaccine design is poised to further enhance precision in cancer vaccine development. As GU malignancies remain a leading cause of cancer-related morbidity and mortality, mRNA and DNA vaccine strategies represent a promising and rapidly evolving area of investigation in oncology. Full article

(This article belongs to the Special Issue Feature Papers of DNA and mRNA Vaccines)

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16 pages, 3516 KB

Open AccessArticle

TCR-T Cell Recognition of an NY-ESO-1 Epitope Presented by HLA-A2 Supertype: Implications for Cancer Immunotherapy

by Qingqing Lin, Fenglan Liu, Yipeng Ma, Yanwei Li, Tong Lin, Xiaochun Chen, Jinling Zhang, Heng Sun, Zhi Wang, Xiaojun Xia, Geng Tian, Shi Jin and Mingjun Wang

Vaccines 2025, 13(9), 898; https://doi.org/10.3390/vaccines13090898 - 25 Aug 2025

Abstract

Background: T-cell receptor (TCR)-engineered T-cell therapy (TCR-T) has become a promising anticancer therapy. Recognition of tumor cells by TCR-T cells requires matched human leukocyte antigen (HLA) alleles and tumor antigens, which seriously limits their population coverage. One strategy to expand the population coverage [...] Read more.

Background: T-cell receptor (TCR)-engineered T-cell therapy (TCR-T) has become a promising anticancer therapy. Recognition of tumor cells by TCR-T cells requires matched human leukocyte antigen (HLA) alleles and tumor antigens, which seriously limits their population coverage. One strategy to expand the population coverage of a specific TCR-T cell therapy is to enable TCR-T cells to recognize target peptides presented by more HLA alleles. Methods: In this study, HLA alleles were selected based on the Chinese population frequency and HLA supertype classification. Then, COS-7 and two tumor cell lines (586 mel and 5637) were transduced with selected HLA alleles for functional evaluation of TCR-T cells. HLA-A2 alleles capable of both exogenously and endogenously presenting the NY-ESO-1-derived epitope and thereby being recognized by TCR-T cells were tested. Results: We demonstrated that a given TCR-T cell product can recognize the NY-ESO-1 peptide exogenously and endogenously presented not only by HLA-A*02:01 but also by HLA-A*02:03, HLA-A*02:06, and HLA-A*02:10, almost doubling the population coverage in the Chinese population from 12.01% to 21.05%. Conclusions: Our study suggests that cancer patients expressing members of the HLA-A2 supertype may benefit from the TCR-T cell product, and other TCR-T cell products could similarly expand their population coverage even within the non-Chinese population through an analogous approach. Full article

(This article belongs to the Section Vaccination Against Cancer and Chronic Diseases)

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16 pages, 2673 KB

Open AccessArticle

Immunogenic Responses Elicited by a Pool of Recombinant Lactiplantibacillus plantarum NC8 Strains Surface-Displaying Diverse African Swine Fever Antigens Administered via Different Immunization Routes in a Mouse Model

by Assad Moon, Hongxia Wu, Tao Wang, Lian-Feng Li, Yongfeng Li, Zhiqiang Xu, Jia Li, Yanjin Wang, Jingshan Huang, Tianqi Gao, Yuan Sun and Hua-Ji Qiu

Vaccines 2025, 13(9), 897; https://doi.org/10.3390/vaccines13090897 - 25 Aug 2025

Abstract

Background: African swine fever (ASF) is a highly contagious and often deadly disease that poses a major threat to swine production worldwide. The lack of a commercially available vaccine underscores the critical need for innovative immunization strategies to combat ASF. Methods: Six ASFV [...] Read more.

Background: African swine fever (ASF) is a highly contagious and often deadly disease that poses a major threat to swine production worldwide. The lack of a commercially available vaccine underscores the critical need for innovative immunization strategies to combat ASF. Methods: Six ASFV antigenic proteins (K78R, A104R, E120R, E183L, D117L, and H171R) were fused with the Lactiplantibacillus plantarum WCFS1 surface anchor LP3065 (LPxTG motif) to generate recombinant Lactiplantibacillus plantarum NC8 (rNC8) strains. The surface expression was confirmed using immunofluorescence and Western blotting assays. Additionally, the dendritic cell-targeting peptides (DCpep) were co-expressed with each antigen protein. Mice were immunized at a dosage of 10⁹ colony-forming units (CFU) per strain per mouse via intragastric (I.G.), intranasal (I.N.), and intravenous (I.V.) routes. The bacterial mixture was heat-inactivated by boiling for 15 min to destroy viable cells while preserving antigenic structures. I.V. administration caused no hypersensitivity, confirming the method’s safety and effectiveness. Results: Following I.G. administration, rNC8-E120R, rNC8-E183L, rNC8-K78R, and rNC8-A104R induced significant levels of secretory immunoglobulin A (sIgA) in fecal samples, whereas rNC8-H171R and rNC8-D117L failed to induce a comparable response. Meanwhile, rNC8-D117L, rNC8-K78R, and rNC8-A104R also elicited significant levels of sIgA in bronchoalveolar lavage fluid (BALF). Following I.N. immunization, rNC8-E120R, rNC8-K78R, and rNC8-A104R significantly increased sIgA levels in both fecal and BALF immunization. In contrast, I.V. immunization with heat-inactivated rNC8-K78R and rNC8-A104R induced robust serum IgG titers, whereas the remaining antigens elicited minimal or insignificant responses. Flow cytometry analysis revealed expanded CD3⁺CD4⁺ T cells in mice immunized via the I.N. and I.G. and CD3⁺CD4⁺ T cells only in those immunized via the I.N. route. Th1 responses were also significant in the sera of mice immunized via the I.G. and I.N. routes. Conclusions: The rNC8 multiple-antigen cocktail elicited strong systemic and mucosal immune responses, providing a solid foundation for the development of a probiotic-based vaccine against ASF. Full article

(This article belongs to the Special Issue Vaccines for Porcine Viruses)

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16 pages, 263 KB

Open AccessArticle

Acceptance of Nirsevimab for the Prevention of Respiratory Syncytial Virus Infection in Neonates: A Cross-Sectional Survey in Emilia-Romagna, Italy

by Susanna Esposito, Valentina Fainardi, Maria Elena Capra, Melodie Aricò, Angela Lanzoni, Beatrice Rita Campana, Marta Niceforo, Cosimo Neglia, Enrico Valletta, Giacomo Biasucci and Serafina Perrone

Vaccines 2025, 13(9), 896; https://doi.org/10.3390/vaccines13090896 - 23 Aug 2025

Abstract

Background: Respiratory syncytial virus (RSV) bronchiolitis remains a leading cause of hospitalization in infants, particularly those with risk factors such as prematurity or chronic diseases. Nirsevimab, a long-acting monoclonal antibody, has recently been approved for RSV prevention. However, parental acceptance of this [...] Read more.

Background: Respiratory syncytial virus (RSV) bronchiolitis remains a leading cause of hospitalization in infants, particularly those with risk factors such as prematurity or chronic diseases. Nirsevimab, a long-acting monoclonal antibody, has recently been approved for RSV prevention. However, parental acceptance of this novel immunoprophylaxis is crucial for effective implementation. The aim of this study was to investigate parental acceptance of nirsevimab prophylaxis for RSV among eligible neonates in Emilia-Romagna, Italy, and to identify factors influencing decision making. Methods: A prospective, multicenter observational study enrolled 1042 parents of neonates eligible for nirsevimab prophylaxis according to regional criteria. Parents completed a semi-structured questionnaire during pre-immunization counseling, exploring knowledge, attitudes, perceived risks, information sources, and willingness to accept prophylaxis. Statistical analysis assessed associations between parental characteristics and acceptance rates. Results: Among the 1042 respondents, 87.0% (n = 907) expressed willingness to administer nirsevimab to their child, while 2.2% (n = 23) refused and 8.8% (n = 92) were undecided. Higher acceptance was significantly associated with awareness of RSV risks (72.1% vs. 41.7%, p < 0.01), belief in nirsevimab’s high efficacy (46.2% vs. 18.3%, p < 0.01), and lower concern over side effects (10.6% vs. 27.8%, p < 0.01). Trust in primary care pediatricians and the healthcare system was also notably higher among accepting parents (p < 0.001). Willingness to pay declined with a hypothetical EUR 250 cost but remained higher among the acceptance group (71.0% vs. 50.4%, p < 0.001). Conclusions: Parental acceptance of nirsevimab in Emilia-Romagna was high, though significant gaps in knowledge and concerns about safety persist. Targeted educational strategies that clarify the nature, efficacy, and safety of nirsevimab—alongside maintaining cost-free access—are essential to support the successful implementation of RSV prophylaxis programs. Full article

(This article belongs to the Special Issue Pediatric Vaccinations)

28 pages, 2489 KB

Open AccessReview

Role of the Virome in Vaccine-Induced Immunization

by Rossella Cianci, Mario Caldarelli, Paola Brani, Annalisa Bosi, Alessandra Ponti, Cristina Giaroni and Andreina Baj

Vaccines 2025, 13(9), 895; https://doi.org/10.3390/vaccines13090895 - 23 Aug 2025

Abstract

The human virome—comprising viruses that can persist in a host, those that benefit the host, and those that remain latent—has gained increasing acceptance as a modulator of immune response toward vaccination. The factors known to influence vaccine efficacy include host genetics, age, and [...] Read more.

The human virome—comprising viruses that can persist in a host, those that benefit the host, and those that remain latent—has gained increasing acceptance as a modulator of immune response toward vaccination. The factors known to influence vaccine efficacy include host genetics, age, and bacterial microbiota, while the virome is a much less considered fourth dimension. This article reviews how components of the virome such as Torque Teno Virus (TTV), cytomegalovirus (CMV), Epstein–Barr virus (EBV), and bacteriophages impact both innate and adaptive immune responses, including mechanisms of immune pre-activation, trained immunity, and molecular mimicry from both beneficial and detrimental perspectives for vaccine-induced immunization. Emphasis is given to immunocompromised populations such as transplant recipients and those with HIV, where virome composition has been shown to correlate with vaccine responsiveness. Experimental models support clinical observations on how chronic viral exposures can either enhance or inhibit vaccine efficacy. Finally, we discuss virome-aware precision vaccinology and call for the integration of the virome in the development of immunization strategies, thus improving outcomes through customization. Full article

(This article belongs to the Special Issue Clinical Strategies to Improve Efficacy, Effectiveness, and Safety of Vaccination in Humans)

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12 pages, 231 KB

Open AccessReview

Review of Human Papillomavirus Vaccination Programs in United States Schools

by Cassandra Duran, Aditi Gupta, Lynda Aririguzo, Norma Castillo and Sanghamitra M. Misra

Vaccines 2025, 13(9), 894; https://doi.org/10.3390/vaccines13090894 - 23 Aug 2025

Abstract

Background: School vaccination programs (school-based and school-located) that include the human papillomavirus (HPV) vaccine have been implemented throughout the United States since 2009. Methods: We conducted a review of school HPV vaccination programs in PUBMED, Google Scholar, Web of Science, Ovid, Medline, and [...] Read more.

Background: School vaccination programs (school-based and school-located) that include the human papillomavirus (HPV) vaccine have been implemented throughout the United States since 2009. Methods: We conducted a review of school HPV vaccination programs in PUBMED, Google Scholar, Web of Science, Ovid, Medline, and Embase and included peer-reviewed studies originating in the United States that focused on any aspect of HPV school vaccination programs. Results: Our review yielded 47 articles that fell into several categories: (1) parent and child perceptions, (2) school nurse perceptions, (3) development, (4) implementation, (5) outcomes, and (6) barriers and facilitators of HPV vaccination programs in schools. Conclusions: School vaccination programs including the HPV vaccine have been implemented successfully all over the United States. Overall, nurse, parent, and student perceptions are positive, but there are various barriers to program success. Successes and failures of school HPV vaccination programs should be examined to develop best practices to sustain and expand these impactful programs. Full article

(This article belongs to the Special Issue HPV Vaccination Coverage: Problems and Challenges)

28 pages, 2825 KB

Open AccessReview

The Central Importance of Vaccines to Mitigate the Threat of Antibiotic-Resistant Bacterial Pathogens

by Jiaqi Amber Zhang and Victor Nizet

Vaccines 2025, 13(9), 893; https://doi.org/10.3390/vaccines13090893 - 23 Aug 2025

Abstract

Antibiotics have dramatically reduced the burden of infectious diseases since their discovery, but the accelerating rise in antimicrobial resistance (AMR) now threatens these gains. AMR was responsible for nearly 5 million deaths in 2023 and continues to undermine the efficacy of existing treatments, [...] Read more.

Antibiotics have dramatically reduced the burden of infectious diseases since their discovery, but the accelerating rise in antimicrobial resistance (AMR) now threatens these gains. AMR was responsible for nearly 5 million deaths in 2023 and continues to undermine the efficacy of existing treatments, particularly in low- and middle-income countries. While efforts to address AMR have focused heavily on antibiotic stewardship and new drug development, vaccines represent a powerful yet underutilized tool for prevention. By reducing the incidence of bacterial infections, vaccines lower antibiotic consumption, interrupt transmission of resistant strains, and minimize the selective pressures that drive resistance. Unlike antibiotics, vaccines offer long-lasting protection, rarely induce resistance, and confer indirect protection through herd immunity. This review examines the global burden and drivers of AMR, highlights the unique advantages of vaccines over antibiotics in mitigating AMR, and surveys the current development pipeline of vaccines targeting key multidrug-resistant bacterial pathogens. Full article

(This article belongs to the Special Issue Vaccines to Reduce Antimicrobial Resistance to Bacterial Pathogens)

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13 pages, 838 KB

Open AccessArticle

Multi-Component Vaccine Candidates Against Non-Typeable Haemophilus influenzae

by Nouria Belkacem, Ala-Eddine Deghmane and Muhamed-Kheir Taha

Vaccines 2025, 13(9), 892; https://doi.org/10.3390/vaccines13090892 - 22 Aug 2025

Abstract

Background: Haemophilus influenzae (Hi), a Gram-negative bacterium, is divided into two broad categories: encapsulated and non-capsulated isolates, also called non-typeable Hi isolates (NTHi). NTHi has become prevalent since the introduction of the vaccine against Hi of serotype b. Hi can cause local [...] Read more.

Background: Haemophilus influenzae (Hi), a Gram-negative bacterium, is divided into two broad categories: encapsulated and non-capsulated isolates, also called non-typeable Hi isolates (NTHi). NTHi has become prevalent since the introduction of the vaccine against Hi of serotype b. Hi can cause local infections on respiratory mucosal surfaces and urogenital infections, which can lead to septic abortion in pregnant women. It can also cause invasive infections such as meningitis and septicemia. Moreover, NTHi isolates are becoming increasingly resistant to antibiotics. Vaccines targeting NTHi are not yet available. As these NTHi isolates are not encapsulated, vaccines should target proteins at the bacterial surface. However, vaccine development is hindered by the high variability of these proteins. We aimed to identify conserved outer membrane proteins (OMPs) for vaccines against NTHi. Methods: We analyzed core-genome multilocus sequence typing (cgMLST) of 1144 genomes of Hi collected between 2017 and 2022 and, of these, identified 514 conserved genes that encoded OMPs. We focused on two specific OMPs: Haem1295, encoding the protein P5 (P5), and Haem1040, encoding the protein 26 (P26). P5 is known to bind human complement regulatory protein factor H (FH), while both P5 and P26 are involved in enhancing immune responses. The genes encoding these proteins were cloned, overexpressed, purified, and tested in both active and passive protection models using systemic infection in mice. Results: P5 and P26 were found to be immunogenic during human infections. Vaccination with these proteins conferred protection against both homologous and heterologous NTHi isolates in mice, suggesting broad cross-protection. Conclusions: P5 and P26 are promising vaccine candidates showing cross-protection against NTHi and offering the additional benefit of targeting bacterial virulence factors, enhancing vaccine efficacy against NTHi isolates. Full article

(This article belongs to the Section Vaccine Design, Development, and Delivery)

9 pages, 1600 KB

Open AccessCommentary

Understanding the Implications of Delaying Seasonal Influenza Vaccine Recommendations: An Industry Perspective

by Steven Rockman and Karen Laurie

Vaccines 2025, 13(9), 891; https://doi.org/10.3390/vaccines13090891 - 22 Aug 2025

Abstract

Multiple studies have assessed the potential for improvement for genetic and antigenic match of influenza vaccines to circulating viruses by altering the timing of vaccine strain decisions. The advent of new technologies for vaccination has generated global discussion around moving the seasonal influenza [...] Read more.

Multiple studies have assessed the potential for improvement for genetic and antigenic match of influenza vaccines to circulating viruses by altering the timing of vaccine strain decisions. The advent of new technologies for vaccination has generated global discussion around moving the seasonal influenza strain recommendations closer to the start of the vaccination period. The window between influenza vaccine strain recommendations and the availability of vaccine supply for immunization comprises sequential processes required to produce vaccine components, reagents for manufacture and release, and regulatory approvals. This commentary examines one company’s perspective on requirements for enabling manufacture and release of seasonal influenza vaccine in more detail, describes preparations to reduce risk, and highlights the potential impact on vaccine supply for all platforms (egg, cell, mRNA) when strain decisions are issued closer to the desired vaccination timing. Full article

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25 pages, 2047 KB

Open AccessReview

Influenza Virus: Global Health Impact, Strategies, Challenges, Role of Nanotechnolgy in Influenza Vaccine Development

by Shabi Parvez, Anushree Pathrathota, Arjun L. Uppar, Ganesh Yadagiri and Shyam Lal Mudavath

Vaccines 2025, 13(9), 890; https://doi.org/10.3390/vaccines13090890 - 22 Aug 2025

Abstract

Influenza is a serious and global health issue, and it is a major cause of morbidity, fatality, and economic loss every year. Seasonal vaccines exist but are not very effective due to strain mismatches, delays in production, and antigenic drift. This comprehensive overview [...] Read more.

Influenza is a serious and global health issue, and it is a major cause of morbidity, fatality, and economic loss every year. Seasonal vaccines exist but are not very effective due to strain mismatches, delays in production, and antigenic drift. This comprehensive overview discusses the current situation of influenza vaccination, including the numerous types of vaccines—inactivated, live attenuated, and recombinant vaccines—and their effectiveness, efficacy, and associated challenges. It highlights the effects of the COVID-19 pandemic on the trends of influenza vaccination and the level to which innovation should be practiced. In the future universal influenza vaccines will be developed that target conserved viral antigens to provide long-term protection to people. In the meantime, novel vaccine delivery platforms, such as mRNA technology, virus-like particle (VLP), and nanoparticle-based systems, and less cumbersome and invasive administration routes, as well as immune responses are also under development to increase access and production capacity. Collectively, these innovations have the potential to not only reduce the global influenza epidemic but also to change the way influenza is prevented and prepare the world for a pandemic. Full article

(This article belongs to the Special Issue Vaccine Development for Influenza Virus)

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16 pages, 912 KB

Open AccessArticle

Peptide-Based Anti-PCSK9 Product for Long-Lasting Management of Hypercholesterolemia

by Suresh R. Giri, Akshyaya Chandan Rath, Chitrang J. Trivedi, Bibhuti Bhusan Bhoi, Sandip R. Palode, Vighnesh N. Jadhav, Hitesh Bhayani, Avanishkumar Singh, Chintan Patel, Tushar M. Patel, Niraj M. Sakhrani, Jitendra H. Patel, Niraj A. Shah, Rajendra Chopade, Rajesh Bahekar, Vishwanath Pawar, Rajesh Sundar, Sanjay Bandyopadhyay and Mukul R. Jain

Vaccines 2025, 13(9), 889; https://doi.org/10.3390/vaccines13090889 - 22 Aug 2025

Abstract

Background/Objectives: Hypercholesterolemia remains a major risk factor for cardiovascular disease and a leading cause of global mortality. Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes degradation of low-density lipoprotein receptors (LDLR), thereby reducing LDL-cholesterol (LDL-C) clearance. While monoclonal antibodies (mAbs) targeting PCSK9 are effective, [...] Read more.

Background/Objectives: Hypercholesterolemia remains a major risk factor for cardiovascular disease and a leading cause of global mortality. Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes degradation of low-density lipoprotein receptors (LDLR), thereby reducing LDL-cholesterol (LDL-C) clearance. While monoclonal antibodies (mAbs) targeting PCSK9 are effective, their short half-life requires frequent dosing and incurs high treatment costs. This study evaluates a novel peptide-based Anti-PCSK9 product aimed at providing sustained LDL-C reduction. Methods: A novel PCSK9 based-peptide conjugated to diphtheria toxoid (DT) was evaluated in various preclinical models: high-fat diet-fed C57BL/6 mice, APOB100/hCETP transgenic mice, BALB/c mice and normocholesterolemic non-human primates. Immunogenicity (Anti-PCSK9 antibody titers, binding affinity by SPR), pharmacodynamics (LDL-C levels, inhibition of PCSK9-LDLR interaction) and safety were assessed. Toxicity was evaluated in rodents, rabbits and dogs through clinical monitoring, histopathology, organ function and safety pharmacology studies. Results: The Anti-PCSK9 product induced robust and long-lasting immune response in all models antibody titers in BALB/c mice peaked by week 6 and persisted for 12 months. LDL-C reductions of 44% in APOB100/hCETP mice and 37% in C57BL/6 mice correlated with high antibody titers and strong PCSK9-binding affinities (85 and 49 RU), leading to 59% and 58% inhibition of PCSK9-LDLR interaction, respectively. Non-human primates showed sustained responses. No systemic toxicity was observed; injection-site reactions were mild and reversible. No adverse effects were detected on cardiovascular, neurological, or respiratory systems. Conclusions: This peptide-based Anti-PCSK9 therapy offers sustained efficacy and safety, representing a promising long-acting alternative for managing hypercholesterolemia. Full article

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

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15 pages, 272 KB

Open AccessReview

A Review of Insights on Vaccination Against Respiratory Viral Infections in Africa: Challenges, Efforts, Impacts, and Opportunities for the Future

by Paul Gasana, Noel Gahamanyi, Augustin Nzitakera, Frédéric Farnir, Daniel Desmecht and Leon Mutesa

Vaccines 2025, 13(9), 888; https://doi.org/10.3390/vaccines13090888 - 22 Aug 2025

Abstract

Background: Respiratory viral infections such as influenza, COVID-19, and respiratory syncytial virus (RSV) are considered as major public health threats in Africa. Despite global advancements in vaccine development, persistent inequities in access, delivery infrastructure, and public trust limit the continent’s capacity to [...] Read more.

Background: Respiratory viral infections such as influenza, COVID-19, and respiratory syncytial virus (RSV) are considered as major public health threats in Africa. Despite global advancements in vaccine development, persistent inequities in access, delivery infrastructure, and public trust limit the continent’s capacity to control these diseases effectively. This review aimed at providing insights on challenges, efforts, impacts, and opportunities for the future related to vaccination against respiratory viral infections in Africa. Methods: This narrative review synthesizes the peer-reviewed literature and global health reports to examine vaccination efforts against respiratory viruses in Africa. The analysis focuses on disease burden, vaccine coverage, barriers to uptake, enabling factors, progress in local vaccine production, and strategies for integrating vaccines into national immunization programs (NIPs). Results: Respiratory vaccines have significantly reduced hospitalizations and mortality among high-risk groups in African countries. Nonetheless, key challenges, including limited cold chain capacity, vaccine hesitancy, donor-reliant supply chains, and under-resourced health systems, continue to undermine vaccine delivery. Successful interventions include community mobilization, use of mobile health technologies, and leveraging existing immunization platforms. Emerging initiatives in local vaccine manufacturing, including Rwanda’s modular mRNA facility and Senegal’s Institut Pasteur, signal a shift toward regional self-reliance. Conclusions: Maximizing the impact of respiratory vaccines in Africa requires a multifaceted strategy: integrating vaccines into NIPs, strengthening domestic production, expanding cold chain and digital infrastructure, and addressing sociocultural barriers through community-driven communication. These efforts are essential to achieving vaccine equity, health resilience, and pandemic preparedness across the continent. Full article

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

14 pages, 4701 KB

Open AccessArticle

A QS21+ CpG-Adjuvanted Rabies Virus G Subunit Vaccine Elicits Superior Humoral and Moderate Cellular Immunity

by Han Cao, Hui Li, Wenzhi Liu, Ning Luan, Jingping Hu, Meijun Kong, Jie Song and Cunbao Liu

Vaccines 2025, 13(8), 887; https://doi.org/10.3390/vaccines13080887 - 21 Aug 2025

Abstract

Background: Rabies remains a fatal zoonotic disease caused by rabies virus (RABV), posing substantial global health challenges. Current vaccine production faces challenges in manufacturing efficiency and cost-effectiveness. The RABV glycoprotein (RABV-G) serves as the key antigen for eliciting protective immunity. Methods: We developed [...] Read more.

Background: Rabies remains a fatal zoonotic disease caused by rabies virus (RABV), posing substantial global health challenges. Current vaccine production faces challenges in manufacturing efficiency and cost-effectiveness. The RABV glycoprotein (RABV-G) serves as the key antigen for eliciting protective immunity. Methods: We developed a novel QS21+CpG-adjuvanted RABV-G subunit vaccine and systematically compared its performance against three control formulations: mRNA vaccine composed of H270P-targeted mutation packaged in lipid nanoparticles (LNP), named LNP-mRNA-G-H270P, commercial inactivated vaccine, and alum-adjuvanted RABV-G subunit vaccine. Results: The result show that the G+QS21+CpG subunit vaccine elicited superior humoral immunity, as evidenced by significantly higher RABV-G-specific IgG titers and virus-neutralizing antibody responses compared to all other groups. The LNP-mRNA-G-H270P vaccine maintained its expected cellular immunity advantage, with the G+QS21+CpG group exhibiting moderately reduced but still significant levels of IFN-γ-secreting splenocytes and levels of IL-2 in the supernatant of spleen cells, as well as IFN-γ-producing CD4+ T cells. Both LNP-mRNA-G-H270P and G+QS21+CpG vaccine groups provided 100% protection against lethal challenge (50LD₅₀ RABV). Conclusions: These findings provide novel vaccine/adjuvant strategies for rabies while elucidating platform-specific immunogenicity patterns, offering critical insights for pathogens requiring balanced humoral/cellular immunity. Full article

(This article belongs to the Section Vaccine Design, Development, and Delivery)

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15 pages, 3372 KB

Open AccessArticle

Do Family Physicians’ Recommendations for Influenza and Pneumococcal Vaccines Impact the Elderly Aged ≥60 Years? A Cross-Sectional Study in Six Chinese Cities

by Yuxing Wang, Jianing Dai, Shuai Yuan, Ying Chen, Zhujiazi Zhang, Ling Zhu, Gang Liu, Qiang Zeng, Qian Qiu, Chunyu Luo, Rendan Deng and Lili You

Vaccines 2025, 13(8), 886; https://doi.org/10.3390/vaccines13080886 - 21 Aug 2025

Abstract

Background: Influenza vaccine and pneumococcal vaccine are essential to protect the health of older adults. This study focuses on the impact of family physicians’ recommendations on influenza and pneumococcal vaccine uptake among urban Chinese older adults and makes recommendations for improving vaccination [...] Read more.

Background: Influenza vaccine and pneumococcal vaccine are essential to protect the health of older adults. This study focuses on the impact of family physicians’ recommendations on influenza and pneumococcal vaccine uptake among urban Chinese older adults and makes recommendations for improving vaccination rates. Methods: A cross-sectional survey on influenza vaccination and pneumonia vaccination was conducted in December 2024 in six cities in China among adults aged ≥60 years. Marginal effects as well as logistic regression models were adopted to measure the relationship between family physician recommendation and influenza vaccination and pneumonia vaccination. Results: The overall influenza vaccination rate was 34.05% and pneumococcal vaccination rate was 22.79%. City, educational level, monthly income, health status, and family physician vaccination recommendation had significant impacts on influenza and pneumococcal vaccination (p < 0.05). Among the investigated elderly population, 48.78% and 28.56% had received recommendations from family physicians regarding influenza and pneumococcal vaccination, respectively. Analysis of marginal effects models revealed that physicians’ recommendations were significantly able to boost influenza and pneumococcal vaccination rates by 26.3% (average marginal effect = 0.263, 95% CI = 0.249–0.277) and 23.7% (average marginal effect = 0.237, 95% CI = 0.225–0.248), respectively (p < 0.001). In the adjusted model, family physician recommendation, compared with no family physician recommendation, was also associated with vaccine policy, monthly income, and age in influenza vaccine and pneumococcal vaccine uptake. Conclusions: Older adults’ influenza and pneumococcal vaccination rates need to be improved. Family physicians’ recommendations show a more significant impact on older adults. Family physician recommendations had the greatest boosting effect on vaccination among individuals aged 70–79. Healthcare providers should adopt different vaccine recommendation strategies based on the characteristics of older adults. Full article

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

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14 pages, 995 KB

Open AccessArticle

A Phase II Random, Double-Blind, Placebo-Controlled Study of the Safety and Immunogenicity of a Recombinant G Protein-Based Respiratory Syncytial Virus Vaccine in Healthy Older Adults

by Lunan Zhang, Gan Zhao, Xin Cheng, Shuo Wang, Jiarong Wang, Xuefen Huai, Yu Xia, Yanling Xiao, Sulin Ren, Shijie Zhang, Qiao Wang and Bin Wang

Vaccines 2025, 13(8), 885; https://doi.org/10.3390/vaccines13080885 - 21 Aug 2025

Abstract

Background: Respiratory syncytial virus (RSV) poses a significant global health threat, particularly to children and the elderly. While progress has been made in RSV vaccine development, gaps remain, especially in protecting the elderly population. BARS13, a recombinant non-glycosylated G protein-based RSV vaccine, [...] Read more.

Background: Respiratory syncytial virus (RSV) poses a significant global health threat, particularly to children and the elderly. While progress has been made in RSV vaccine development, gaps remain, especially in protecting the elderly population. BARS13, a recombinant non-glycosylated G protein-based RSV vaccine, has shown promise in preclinical and Phase 1 studies. This phase II trial sought to determine whether escalating doses of BARS13 could enhance immune responses while maintaining safety and tolerability in healthy older adults aged 60–80 years. Methods: This study employed a rigorous randomized, double-blind, placebo-controlled design involving 125 participants across two Australian centers. Participants were randomized in a 3:1 (vaccine–placebo) ratio for Cohorts 1–2 (30 active, 10 placebo each) and a 2:1 ratio for Cohort 3 (30 active, 15 placebo). Cohort 1 (low dose) received 10 µg rRSV-G + 10 µg CsA in one arm + a placebo in the other (Days 1 and 29); Cohort 2 (high dose) received 10 µg rRSV-G + 10 µg CsA in both arms (20 µg total per dose, Days 1 and 29); Cohort 3 (multi-dose) received the same dose as that of Cohort 2 but with a third dose on Day 57. The placebo groups received IM injections in both arms at matching timepoints. The primary endpoints included safety and tolerability assessments, while the secondary endpoints evaluated the RSV G protein-specific IgG antibody concentrations using enzyme-linked immunosorbent assays (ELISAs). Statistical analysis was performed on both the safety and immunogenicity populations. Results: BARS13 was well-tolerated across all cohorts, with no serious adverse events (SAEs) related to the vaccine. The most common adverse events were mild local reactions (pain and tenderness) and systemic reactions (headache and fatigue), which resolved within 24–48 h. Immunogenicity analysis demonstrated a dose-dependent increase in the RSV G protein-specific IgG geometric mean concentrations (GMCs). Cohort 3, which received multiple high-repeat dose administrations, showed the highest immune response, with the IgG GMC rising from 1195.4 IU/mL on Day 1 to 1681.5 IU/mL on Day 113. Response rates were also the highest in Cohort 3, with 86.2% of participants showing an increase in antibody levels by Day 29. Conclusions: BARS13 demonstrated a favorable safety profile and strong immunogenicity in elderly participants, with a clear dose-dependent antibody response. These results support further development of BARS13 as a potential RSV vaccine candidate for the elderly. Further studies are needed to evaluate the long-term efficacy and optimal dosing schedule. Full article

(This article belongs to the Special Issue Clinical Strategies to Improve Efficacy, Effectiveness, and Safety of Vaccination in Humans)

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11 pages, 280 KB

Open AccessArticle

Participation in a Voluntary Blood Donation Program as an Opportunity to Assess and Enhance Tetanus Immunity in Adult Blood Donors with an Outdated or Unknown Vaccination Status

by Katarzyna Tkaczyszyn, Małgorzata Szymczyk-Nużka and Leszek Szenborn

Vaccines 2025, 13(8), 884; https://doi.org/10.3390/vaccines13080884 - 21 Aug 2025

Abstract

Background/Objectives: Booster vaccination coverage in the adult population in Poland remains insufficient. The objective of this study was to utilize the opportunity of a visit to the Regional Blood Transfusion Center in Wroclaw—associated with blood donation—as a means to remind individuals about the [...] Read more.

Background/Objectives: Booster vaccination coverage in the adult population in Poland remains insufficient. The objective of this study was to utilize the opportunity of a visit to the Regional Blood Transfusion Center in Wroclaw—associated with blood donation—as a means to remind individuals about the need for tetanus booster vaccination and to assess tetanus immunity in healthy adults (30–40 years after their last mandatory dose) who had not received booster immunizations. Materials and Methods: A total of 97 blood donors aged 50 to 64 years (median age: 54 years) were enrolled, of whom 78% were male. 1. Tetanus immunity was assessed by a single measurement of serum anti-tetanus IgG antibody concentration. 2. A questionnaire was used to collect data relevant to tetanus immune status. 3. Individuals with insufficient protection received a booster dose of the tetanus vaccine, and the post-vaccination serologic response was evaluated. Results: 1. In the study group, 10.3% of participants had no protective immunity against Clostridium tetani, while 5.2% exhibited uncertain protection. An additional 32% demonstrated antibody levels conferring only short-term protection. Satisfactory protection—defined as immunity lasting at least 3 years—or long-term protection (at least 5 years) was identified in 52.5% of patients. Although 72% of donors reported receiving mandatory childhood immunizations, only 5% could provide medical documentation. In this subgroup, a significantly higher geometric mean antibody concentration was observed (0.69 vs. 0.52 IU/mL; p = 0.04), and significantly fewer participants required immediate post-exposure prophylaxis (1/39 vs. 14/54; p = 0.003). 2. Among the 46 individuals eligible for a booster dose, 17 (37%) returned for vaccination. Of these, 16 (94%) achieved antibody titers consistent with long-term protection following a single vaccine dose. Conclusions: Tetanus immunity among adults is heterogeneous and difficult to predict due to the frequent lack of vaccination records and unreliable self-reported histories. A history of injury and associated surgical wound care involving injection often serves as the only indication of prior vaccination. A single booster dose is highly effective in eliciting a robust immune response in individuals vaccinated during childhood but lacking recent boosters. Rising vaccine hesitancy toward both mandatory and recommended immunizations in Poland negatively influences adult decisions regarding tetanus vaccination. Participation in voluntary blood donation programs presents a valuable opportunity for immunization education, immune status screening, and the implementation of effective catch-up vaccination strategies. Full article

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

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20 pages, 1744 KB

Open AccessArticle

Immunogenic and Protective Properties of mRNA Vaccine Encoding Hemagglutinin of Avian Influenza A/H5N8 Virus, Delivered by Lipid Nanoparticles and Needle-Free Jet Injection

by Vladimir A. Yakovlev, Victoria R. Litvinova, Nadezhda B. Rudometova, Mariya B. Borgoyakova, Elena V. Tigeeva, Ekaterina V. Starostina, Ksenia I. Ivanova, Andrei S. Gudymo, Natalia V. Danilchenko, Olga N. Perfilyeva, Kristina P. Makarova, Danil I. Vahitov, Boris N. Zaitsev, Elena V. Dmitrienko, Sergey V. Sharabrin, Svetlana I. Krasnikova, Lyubov A. Kisakova, Denis N. Kisakov, Tatiana N. Ilyicheva, Vasiliy Yu. Marchenko, Larisa I. Karpenko, Andrey P. Rudometov and Alexander A. Ilyichev Show full author list Hide full author list

Vaccines 2025, 13(8), 883; https://doi.org/10.3390/vaccines13080883 - 21 Aug 2025

Abstract

Background/Objectives: The development of a vaccine against highly pathogenic avian influenza viruses subtype A/H5 is an urgent task due to concerns about its pandemic potential. Methods: In this study, we have developed an experimental mRNA vaccine, mRNA-H5, encoding a modified hemagglutinin trimer of influenza [...] Read more.

Background/Objectives: The development of a vaccine against highly pathogenic avian influenza viruses subtype A/H5 is an urgent task due to concerns about its pandemic potential. Methods: In this study, we have developed an experimental mRNA vaccine, mRNA-H5, encoding a modified hemagglutinin trimer of influenza virus A/turkey/Stavropol/320-01/2020 (H5N8). BALB/c mice were immunized with the mRNA-H5 vaccine using lipid nanoparticles (LNPs) and needle-free jet injection (JI). Subsequently, the immune response to vaccine was assessed using ELISA, microneutralization assay, and ICS methods, and a challenge study was conducted. Results: mRNA-H5 was shown to effectively stimulate specific humoral and T-cell immune responses. Moreover, mRNA-H5 delivered by LNPs and JI provided 100% protection of immunized mice against lethal challenge with homologous and heterologous strains of avian influenza virus (A/Astrakhan/3212/2020 (H5N8) and A/chicken/Magadan/14-7V/2022 (H5N1), respectively). Conclusions: The present results indicate that JI can be considered as an alternative to LNPs for mRNA delivery, and according to the literature, JI is safer than delivery using LNP. mRNA-H5 has potential as a vaccine against infection with highly pathogenic avian influenza A/H5 viruses with pandemic potential. Full article

(This article belongs to the Special Issue Influenza Virus Vaccines and Vaccination)

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