Vaccines

22 pages, 4591 KiB

Open AccessArticle

Immunization with Inactivated Bacillus subtilis Spores Expressing TonB-Dependent Receptor (TBDR) Protects Against Multidrug-Resistant Acinetobacter baumannii Infection

by Amalia A. Saperi, Atiqah Hazan, Nurfatihah Zulkifli, Hai-Yen Lee, Nor-Aziyah MatRahim and Sazaly AbuBakar

Vaccines 2025, 13(6), 616; https://doi.org/10.3390/vaccines13060616 - 6 Jun 2025

Abstract

Background/Objectives: The emergence of multidrug-resistant Acinetobacter baumannii (MDR A. baumannii) as a leading cause of fatal hospital-acquired infections underscores the urgent need for effective vaccines. While oral vaccines using live Bacillus subtilis spores expressing A. baumannii TonB-dependent receptor (TBDR) show promise, biosafety [...] Read more.

Background/Objectives: The emergence of multidrug-resistant Acinetobacter baumannii (MDR A. baumannii) as a leading cause of fatal hospital-acquired infections underscores the urgent need for effective vaccines. While oral vaccines using live Bacillus subtilis spores expressing A. baumannii TonB-dependent receptor (TBDR) show promise, biosafety concerns regarding recombinant spore persistence necessitate alternative strategies. Here, we evaluated chemically inactivated B. subtilis spores displaying TBDR as a safer yet immunogenic vaccine candidate. Methods: Recombinant spores were inactivated using iron-ethanol sporicidal solution and administered to BALB/c mice (8–12 weeks old) to assess safety and immunogenicity. Toxicity was evaluated through clinical monitoring, serum biochemistry, and histopathology. Immune responses were characterized by T/B cell activation, IgG/IgA titers, and mucosal sIgA levels. Protective efficacy was determined by challenging immunized mice with MDR A. baumannii Ab35 and quantifying bacterial loads and examining tissue pathology. Results: The inactivated spores exhibited an excellent safety profile, with no adverse effects on clinical parameters, organ function, or tissue integrity. Immunization induced robust systemic and mucosal immunity, evidenced by elevated CD4+/CD8+ T cells, B cells, and antigen-specific IgG/IgA in serum and mucosal secretions. Following the challenge, vaccinated mice showed significantly reduced pulmonary bacterial burdens (>90% reduction), and preserved lung and spleen architecture compared to controls, which developed severe inflammation and tissue damage. Conclusions: These findings demonstrate that inactivated B. subtilis spores expressing TBDR are a safe, orally administrable vaccine platform that elicits protective immunity against MDR A. baumannii. By addressing biosafety concerns associated with live spores while maintaining efficacy, this approach represents a critical advance toward preventing high-risk nosocomial infections. Full article

(This article belongs to the Section Pathogens-host Immune Interface)

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21 pages, 1626 KiB

Open AccessArticle

A Comparison of Tests for Detecting Prior Exposure to Coxiella burnetii for Use with Q-VAX in Australian Human Q Fever Vaccination

by Stephen Graves, Jennifer Robson, Anja Scholzen, Richard Dzeng, Francisca Powell-Romero, Jennifer Evans, John Stenos, Meg Jeppesen, Milou L. C. E. Kouwijzer, Jordi Lankhof, Susan Raju Paul, Tatiana Proboste Ibertti, Lauren Ball, Helen Powell, Stephanie Wilkinson, Evi van Schuppen, Willemijn J. Anker-Op den Brouw, Rowland Cobbold, Anja Garritsen, Mark C. Poznansky and Ann E. Sluder Show full author list Hide full author list

Vaccines 2025, 13(6), 615; https://doi.org/10.3390/vaccines13060615 - 6 Jun 2025

Abstract

Background/Objectives: Q-VAX vaccine, approved in Australia, prevents Q fever. However, individuals with prior Coxiella burnetii (Cb) infection have an increased risk of adverse reactions, requiring pre-vaccination screening by an intradermal hypersensitivity skin test for cell-mediated immune memory and a serological assay [...] Read more.

Background/Objectives: Q-VAX vaccine, approved in Australia, prevents Q fever. However, individuals with prior Coxiella burnetii (Cb) infection have an increased risk of adverse reactions, requiring pre-vaccination screening by an intradermal hypersensitivity skin test for cell-mediated immune memory and a serological assay for anti-Cb antibodies. The week-long interval for skin test assessment limits efficient vaccination. This study evaluated a standardized interferon-γ release assay (IGRA) as a potential skin test alternative. Methods: Immune assays were compared in Australian populations with different incidences of prior Cb exposure. Cell-mediated immunity was assessed by the Q-VAX skin test and IGRA. Serological status was evaluated with established diagnostic assays. Hypothetical vaccine eligibility decisions using combined IGRA and serology results were compared with actual clinical decisions made using current guidelines. Results: All tests performed better in detecting prior infection than in detecting prior vaccination. Only the IGRA identified all individuals with a known history of Q fever. Agreement between the skin test and IGRA was limited. Moderate agreement was observed between hypothetical vaccine eligibility determinations based on IGRA plus serology results and actual clinical decisions. IGRA-positive but serology- and skin test-negative individuals received Q-VAX without clinically significant side effects, suggesting that elevated IGRA responses alone are not predictive of susceptibility to vaccine reactogenicity. Conclusions: The IGRA is not yet a suitable skin test replacement when assessing eligibility for Q fever vaccination, despite the significant limitations of the latter. We offer recommendations for designing future studies that might allow the development of appropriate guidelines for IGRA use in vaccine eligibility screening. Full article

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

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15 pages, 5946 KiB

Open AccessArticle

Safety and Immunogenicity of a Canine Distemper DNA Vaccine Formulated with Lipid Nanoparticles in Dogs, Foxes, and Raccoon Dogs

by Hong Huo, Han Wang, Shulin Liang, Zilong Wang, Jinming Wang, Qingzhu Wang, Chan Li, Yuting Tao, Jinying Ge, Zhiyuan Wen, Jinliang Wang, Weiye Chen, Xijun Wang, Lei Shuai and Zhigao Bu

Vaccines 2025, 13(6), 614; https://doi.org/10.3390/vaccines13060614 - 6 Jun 2025

Abstract

Background: canine distemper (CD) is a highly contagious and fatal disease caused by canine distemper virus (CDV), posing a significant threat to carnivores. New CDV strain circulation and multi-species infection may lead to the potential dilemma of safety concern and insufficient efficacy of [...] Read more.

Background: canine distemper (CD) is a highly contagious and fatal disease caused by canine distemper virus (CDV), posing a significant threat to carnivores. New CDV strain circulation and multi-species infection may lead to the potential dilemma of safety concern and insufficient efficacy of the commercial modified live vaccines. Safe and effective vaccines for canine and wildlife prevention of CD need to be continuously updated and developed. Methods: we developed two DNA vaccines, p17F-LNP and p17H-LNP, encoding the fusion protein (F) or hemagglutinin protein (H) of a field CDV strain (HLJ17) and encapsulated in lipid nanoparticles (LNPs). Serum neutralizing antibody (NAb) was evaluated via neutralization tests, and mouse serum cytokine detection were evaluated via ELISA. Results: immunization of p17F-LNP and p17H-LNP monovalent or bivalent were safe, and induced robust CDV NAb and cytokine responses in mice. LNP encapsulation improved immune responses compared to naked DNA formulation, and the bivalent formulation of p17F-LNP and p17H-LNP (p17F/H-LNP) exhibited synergistic effects with a high level of immune responses. Moreover, two doses of p17F/H-LNP induced long-lasting CDV NAb for over 300 days in dogs, and prime and boost NAb responses in foxes and raccoon dogs. Conclusions: the preliminary findings provided here warrant further development of the p17F/H-LNP vaccine for animal targets against CDV infection. Full article

(This article belongs to the Special Issue Oral and Nucleic Acid Vaccines for Zoonotic and Animal Infectious Diseases)

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5 pages, 130 KiB

Open AccessEditorial

Editors’ Introduction: Understanding and Addressing Vaccine Hesitancy

by Gary L. Kreps, Xuewei Chen and Ming Li

Vaccines 2025, 13(6), 613; https://doi.org/10.3390/vaccines13060613 - 6 Jun 2025

Abstract

The goal of this Special Issue, “Understanding and Addressing Vaccine Hesitancy”, is to examine the current state of knowledge concerning the major causes and influences of vaccine hesitancy, as well as to suggest evidence-based solutions for the growing problem of vaccine hesitancy in [...] Read more.

The goal of this Special Issue, “Understanding and Addressing Vaccine Hesitancy”, is to examine the current state of knowledge concerning the major causes and influences of vaccine hesitancy, as well as to suggest evidence-based solutions for the growing problem of vaccine hesitancy in modern society [...] Full article

(This article belongs to the Special Issue Understanding and Addressing Vaccine Hesitancy)

17 pages, 498 KiB

Open AccessReview

Broadly Neutralizing Antibody Characteristics in Hepatitis C Virus Infection and Implications for Vaccine Design

by Nicole E. Skinner

Vaccines 2025, 13(6), 612; https://doi.org/10.3390/vaccines13060612 - 6 Jun 2025

Abstract

Despite the use of direct-acting antiviral medications to treat hepatitis C virus (HCV), over a million people are newly infected each year, highlighting the need for a prophylactic vaccine. Due to the remarkable genetic diversity of HCV and its many immune evasion mechanisms, [...] Read more.

Despite the use of direct-acting antiviral medications to treat hepatitis C virus (HCV), over a million people are newly infected each year, highlighting the need for a prophylactic vaccine. Due to the remarkable genetic diversity of HCV and its many immune evasion mechanisms, an effective vaccine will need to elicit broadly neutralizing antibodies (bNAb). In addition to providing evidence that a prophylactic HCV vaccine is feasible, this review provides an overview of known HCV bNAb targets, common antibody sequence features associated with broad neutralization, and mechanisms of immune escape. Ongoing knowledge gaps in the field and promising future directions are also discussed. Full article

(This article belongs to the Special Issue

Vaccines and Antibody-Based Therapeutics Against Infectious Disease

)

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14 pages, 605 KiB

Open AccessArticle

Women’s Empowerment and Gender-Related Factors Associated with Maternal Tetanus Protection in 39 Low- and Middle-Income Countries

by Katherine Kirkby, Luisa Arroyave, Franciele Hellwig, M. Carolina Danovaro-Holliday, Nasir Yusuf, Shirin Heidari, Stephanie Shendale, Aluísio J. D. Barros and Ahmad Reza Hosseinpoor

Vaccines 2025, 13(6), 610; https://doi.org/10.3390/vaccines13060610 - 6 Jun 2025

Abstract

Background: Tetanus is a vaccine-preventable disease, and therefore vaccination of women of reproductive age or during pregnancy is recommended alongside childhood tetanus vaccination. Gender-related factors related to social empowerment have been established as determinants of health service utilization; however, these social determinants have [...] Read more.

Background: Tetanus is a vaccine-preventable disease, and therefore vaccination of women of reproductive age or during pregnancy is recommended alongside childhood tetanus vaccination. Gender-related factors related to social empowerment have been established as determinants of health service utilization; however, these social determinants have not yet been explored directly with tetanus vaccination. In response, the aim of this study was to assess overall and country-specific gender-related barriers to maternal tetanus vaccine coverage. Methods: We used data from Demographic and Health Surveys (DHS) in 39 countries implemented between 2013 and 2022. Women’s empowerment was measured through three domains of the Survey-based Women’s emPowERment index (SWPER), as well as other gender-related variables. To assess the association between measures of women’s empowerment and gender-related factors and maternal tetanus immunization coverage, we used multilevel logistic models with pooled data from the 39 countries to analyze overall patterns, and we used multivariable logistic regression for each country-specific dataset to analyze country-level associations. Results: There were notable variations in the factors associated with tetanus vaccination across countries. Overall, we observed that higher levels of women’s empowerment, as measured through social independence and decision-making autonomy using the SWPER index, were associated with higher odds of maternal tetanus protection, with adjusted odds ratios of 1.23 (95%CI: 1.10–1.37) and 1.20 (95%CI: 1.02–1.40), respectively. However, women’s empowerment related to attitude to violence was not. Higher household wealth was also associated with higher odds of maternal tetanus protection overall. Conclusions: Women’s empowerment can improve the uptake of maternal tetanus vaccine. Addressing gender-related barriers may enhance vaccination coverage and contribute to the elimination of maternal and neonatal tetanus as a public health problem. However, these barriers vary from country to country, necessitating country-specific investigations to formulate tailored recommendations. Full article

(This article belongs to the Special Issue Inequality in Immunization 2025)

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18 pages, 621 KiB

Open AccessArticle

Antibody Kinetics of Immunological Memory in SARS-CoV-2-Vaccinated Healthcare Workers—The ORCHESTRA Project

by Seyedalireza Seyedi, Sara Sottile, Mahsa Abedini, Paolo Boffetta, Francesco Saverio Violante, Vittorio Lodi, Giuseppe De Palma, Emma Sala, Marcella Mauro, Francesca Rui, Stefano Porru, Gianluca Spiteri, Luigi Vimercati, Luigi De Maria, Pere Toran-Monserrat, Concepción Violán, Eleonóra Fabiánová, Jana Oravec Bérešová, Violeta Calota and Andra Neamtu

Vaccines 2025, 13(6), 611; https://doi.org/10.3390/vaccines13060611 - 5 Jun 2025

Abstract

Background/Objectives: This study examines the longitudinal dynamics of anti-nucleocapsid (anti-N) and anti-spike (anti-S) antibody responses to SARS-CoV-2 infection and mRNA vaccination based on 81,878 serum samples from 23,616 healthcare workers (HCWs) across five European countries. It includes data across four scheduled vaccine doses—predominantly [...] Read more.

Background/Objectives: This study examines the longitudinal dynamics of anti-nucleocapsid (anti-N) and anti-spike (anti-S) antibody responses to SARS-CoV-2 infection and mRNA vaccination based on 81,878 serum samples from 23,616 healthcare workers (HCWs) across five European countries. It includes data across four scheduled vaccine doses—predominantly BNT162b2—with 25% of samples originating from individuals with confirmed prior infection, as evidenced by elevated anti-S levels, positive Anti-N antibodies, or PCR results. Methods: The study employed a shifted transformation method for data normalization and utilized the Bass diffusion model to predict antibody titer dynamics influenced by both internal factors—such as immune activation contextualized through sociodemographic issues—and external factors, including infection and vaccination. Despite the absence of direct measurements for some internal variables, the model effectively inferred their impact, enabling a rigorous and nuanced delineation of immune response profiles. Results: The Bass diffusion model rigorously captured variations in antibody titers, analyzed through demographic factors such as gender, age, and job role, while thoroughly accounting for pre-infection status. The results indicate that Anti-N antibodies, exclusively produced post-infection, exhibited a rapid decline, while anti-S antibodies, generated from both infection and vaccination, demonstrated prolonged persistence. A significant decline in anti-S levels was observed 3–5 months post-vaccination, with adaptive immunity—characterized by the dominance of internal factors effects relative to external ones—achieved in most groups after the fourth dose. However, adaptive immunity post second dose was limited to specific demographics. Conclusions: These findings emphasize the significance of the Bass Method in predicting vaccine-induced, hybrid immune responses and detecting adaptive immunity by overcoming limitations in internal factor data, thereby advancing effective vaccination and infection control strategies during public health crises. These findings highlight the Bass Method’s value in predicting vaccine-induced and hybrid immunity, effectively addressing internal factor data gaps to enhance vaccination and infection control strategies. Full article

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

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23 pages, 1127 KiB

Open AccessArticle

Effects of Different Adjuvants on the Protective Efficacy of a Subcellular Vaccine Against Chlamydia abortus Infection in Sheep

by Morag Livingstone, Kevin Aitchison, Javier Palarea-Albaladejo, Sergio Gastón Caspe, Clare Underwood, Holly Hill, Cameron Cunnea, Kelly Stronach, Francesca Chianini, Gary Entrican, Sean Ranjan Wattegedera and David Longbottom

Vaccines 2025, 13(6), 609; https://doi.org/10.3390/vaccines13060609 - 5 Jun 2025

Abstract

Background/Objective: Recently, we published three studies describing the development and optimization of a new, safe, and efficacious vaccine to protect sheep from ovine enzootic abortion, which is caused by the zoonotic pathogen Chlamydia abortus. The vaccine, which can be delivered through a [...] Read more.

Background/Objective: Recently, we published three studies describing the development and optimization of a new, safe, and efficacious vaccine to protect sheep from ovine enzootic abortion, which is caused by the zoonotic pathogen Chlamydia abortus. The vaccine, which can be delivered through a single inoculation, is based on a detergent-extracted outer membrane protein (chlamydial outer membrane complex or COMC) preparation of the pathogen. This study aimed to optimize the vaccine further by comparing the effects of different adjuvants on protective efficacy. Methods: We evaluated the effectiveness of three different vaccines (2.5 µg COMC) formulated with one of three adjuvants (Montanide ISA 70VG, Montanide ISA 61VG, and QuilA) to reduce the rate of abortion, placental load and pathology, and post-partum vaginal shedding of organisms in comparison to our benchmark 20 µg COMC/Montanide ISA 70 VG vaccine and a challenge control group of animals. The humoral and cellular immunological responses to vaccination and to challenge were also assessed. Results: The two low-dose Montanide formulated vaccines resulted in low abortion rates of 3.2 and 8.1% for ISA 70 VG and ISA 61 VG, respectively, which were comparable to the benchmark vaccine group (2.7%) and considerably lower than the QuilA (23.7%) and challenge control (36.8%) groups. Similarly, the Montanide-adjuvanted groups had much lower bacterial loads (range: 136–431 genome copies) on vaginal swabs post-parturition than the QuilA (8.9 × 10⁴ copies) and challenge control (2.4 × 10⁵ copies) groups. Conclusions: The results showed that both Montanide adjuvants are more effective for maximizing COMC vaccine efficacy than the QuilA adjuvant and result in much lower bacterial shedding of the pathogen post-parturition, which is important for minimizing potential transmission to naïve animals. Full article

(This article belongs to the Special Issue Research on Immune Response and Vaccines: 2nd Edition)

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17 pages, 836 KiB

Open AccessReview

Vaccines and Animal Models of Nipah Virus: Current Situation and Future Prospects

by Chaoxiang Lv, Jiayue He, Qiqi Zhang and Tiecheng Wang

Vaccines 2025, 13(6), 608; https://doi.org/10.3390/vaccines13060608 - 4 Jun 2025

Abstract

Nipah virus (NiV) is a highly pathogenic paramyxovirus characterized by zoonotic infection, high mortality, and a lack of effective treatment, posing a serious threat to global public health security. Currently, it still lacks specific treatments or approved vaccines, and is listed as a [...] Read more.

Nipah virus (NiV) is a highly pathogenic paramyxovirus characterized by zoonotic infection, high mortality, and a lack of effective treatment, posing a serious threat to global public health security. Currently, it still lacks specific treatments or approved vaccines, and is listed as a potential pandemic threat pathogen by the World Health Organization. This paper systematically reviews the core progress and challenges of NiV investigation, with a focus on the development of animal models, vaccine development strategies, treatment strategy, and bottlenecks in translational medicine. Additionally, we discuss the strengths and limitations of existing animal models, including ferrets, hamsters, mice, and non-human primates (NHPs), and assess advances in vaccine platforms such as viral vectors, subunit vaccines, and mRNA-based vaccine candidates. The paper critically reviews the challenges facing translational research, conservation correlates, and outbreak preparedness, while also providing future research directions for pandemic preparedness and public health security strategies. Full article

(This article belongs to the Section Veterinary Vaccines)

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26 pages, 6162 KiB

Open AccessArticle

Ethnic Comparisons of Spike-Specific CD4+ T Cells, Serological Responses, and Neutralizing Antibody Titers Against SARS-CoV-2 Variants

by Fani Pantouli, Vanessa Silva-Moraes and Ted M. Ross

Vaccines 2025, 13(6), 607; https://doi.org/10.3390/vaccines13060607 - 4 Jun 2025

Abstract

Background/Objectives: To evaluate how immune responses compare among ethnic groups approximately 2 years after receiving a third dose of COVID-19 vaccine (BNT162b2, mRNA-1273, ChAdOx1or BBIBP-CorV), we tested T cell responses and Spike-specific RBD-antibody titer, and neutralized antibody titer levels utilizing Spectral Flow cytometry, [...] Read more.

Background/Objectives: To evaluate how immune responses compare among ethnic groups approximately 2 years after receiving a third dose of COVID-19 vaccine (BNT162b2, mRNA-1273, ChAdOx1or BBIBP-CorV), we tested T cell responses and Spike-specific RBD-antibody titer, and neutralized antibody titer levels utilizing Spectral Flow cytometry, ELISA, and SARS-CoV-2 pseudotyped-based neutralization assays, respectively. Methods: Forty-four individuals from January–December 2023 were identified within the cohort and were classified into different ethnic backgrounds; Black (N = 13), Asian (N = 14), Caucasian (N = 17). We recognize that the “Asian” group includes diverse subpopulations with distinct genetic and environmental backgrounds, which could not be further stratified due to sample-size limitations. Spike-specific AIM+, CD4+, and CD8+ T cell responses were assessed and evaluated against SARS-CoV-2 variants, including the ancestral Wuhan, Delta, and multiple Omicron subvariants (B1.1529, BA2.86, BA.4/5, and XBB.1). Alongside we tested the RBD-IgG and neutralizing antibody titers against the ancestral Wuhan. Spearman’s correlation analysis was utilized to determine corelative relationships among the AIM+ and CD4+ T cell responses, as well as the RBD-IgG and neutralizing antibody titers. Results: Our results show robust and comparable RBD-IgG and neutralizing antibody titers across all groups, with a significant positive correlation between these two measurements. Significant differences were observed in T-cell activation, with Asian participants exhibiting lower frequencies of Spike-specific CD4+ T cells against SARS-CoV-2 Omicron subvariants and higher frequencies of cytokine-producing CD4+ T cells (TNF-α, IFN-γ, and IL-2) as compared to the Caucasian group. Breakthrough infection status was not fully controlled and may influence these findings. Conclusion: Despite a small sample size and potential confounding by natural infections within our long-time-span sampling, our data suggest persistent cellular and humoral immunity 2 years after vaccination across ethnicities, with notable differences in T cell activation and cytokine profile. These preliminary observations highlight the need for larger, more detailed studies that consider intra-ethnic diversity and hybrid immunity to better understand ethnic differences in COVID-19 vaccine responses. Full article

(This article belongs to the Special Issue 3rd Edition: Safety and Autoimmune Response to SARS-CoV-2 Vaccination)

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37 pages, 477 KiB

Open AccessReview

Recombinant Mycobacterium bovis BCG-Based HIV Vaccine: Failures and Promising Approaches for a Successful Vaccine Strategy

by Joan Joseph-Munné, Milena Maya-Hoyos, Narcís Saubi, Santiago Perez, Miguel Angel Martinez Lopez, Eder Baron and Carlos Yesid Soto

Vaccines 2025, 13(6), 606; https://doi.org/10.3390/vaccines13060606 - 3 Jun 2025

Abstract

During 2022, AIDS claimed a life every minute and about 9.2 million HIV-infected people were not on treatment. In addition, a person living with HIV is estimated to be 20–30 times more susceptible to developing active tuberculosis. Every year, 130,000 infants are newly [...] Read more.

During 2022, AIDS claimed a life every minute and about 9.2 million HIV-infected people were not on treatment. In addition, a person living with HIV is estimated to be 20–30 times more susceptible to developing active tuberculosis. Every year, 130,000 infants are newly infected, with vertical transmission being the main cause of pediatric HIV infection. Thus, the development of an effective, safe, and accessible vaccine for neonates and/or adults is an urgent need to prevent or control HIV infection or progression to AIDS. An effective HIV vaccine should induce long-lasting mucosal immunity, broadly neutralizing antibodies, innate immunity, and robust stimulation of CD4+ and CD8+ T-cell responses. Recombinant BCG is a promising live-attenuated bacterial vaccine vector because of its capacity to stimulate T-cell immunity. As a slow-growing microorganism, it provides prolonged low-level antigenic exposure upon infecting macrophages and APCs, potentially stimulating both effector and memory T-cell responses. BCG is considered safe and is currently administered to 80% of infants in countries where it is part of the national immunization program. Additionally, BCG offers several benefits as a live vaccine vehicle since it is cost-effective, easy to mass-produce, and heat stable. It is also well-suited for newborns, as maternal antibodies do not interfere with its efficacy. Furthermore, BCG has a strong safety profile, having been administered to over three billion people as a TB vaccine. In this review, we provide an extensive summary of the literature relating to immunogenicity studies in animal models performed since 2011. Moreover, we provide a comprehensive analysis of the key factors influencing the design of recombinant BCG as a live vaccine vehicle: (i) expression vectors; (ii) selection of HIV immunogen; (iii) promoters to regulate gene expression; (iv) BCG strain and BCG codon optimization; (v) genetic plasmid stability; (vi) influence of preexisting immunity, route, and dose immunization; and (vii) safety profile. Full article

(This article belongs to the Special Issue The Development of HIV Vaccines: Advances and Challenges)

15 pages, 3706 KiB

Open AccessSystematic Review

Impact of Chemotherapy on Vaccine Immunogenicity and Revaccination Response of Acute Lymphoblastic Leukemia—A Systematic Review and Meta-Analysis

by Yuyuan Zeng, Chuanyu Yang, Xihan Li, Qi An, Bo Zhou, Wenquan Niu, Yu Tian, Yifei Cheng and Lin Wang

Vaccines 2025, 13(6), 605; https://doi.org/10.3390/vaccines13060605 - 1 Jun 2025

Abstract

Background: Chemotherapy, a cornerstone treatment for Acute Lymphoblastic Leukemia (ALL), can compromise immune function, leading to impaired immune memory function and diminished responses to revaccination. This systematic review and meta-analysis sought to evaluate the impact of chemotherapy on the immunogenicity of prior vaccinations [...] Read more.

Background: Chemotherapy, a cornerstone treatment for Acute Lymphoblastic Leukemia (ALL), can compromise immune function, leading to impaired immune memory function and diminished responses to revaccination. This systematic review and meta-analysis sought to evaluate the impact of chemotherapy on the immunogenicity of prior vaccinations and subsequent revaccination responses in children with ALL. Methods: A comprehensive search was conducted through PubMed, Embase, Web of Science, and Medline. Search time was 9 January 2025. R 4.4.2 was employed for data analysis. Results: A total of 29 relevant studies were identified, with 8 undergoing meta-analysis. The pooled antibody seropositive rates (SPR) for vaccines against Hepatitis B Virus (HBV), Hepatitis A Virus (HAV), diphtheria, tetanus, pertussis, measles, mumps, rubella, varicella, and Pneumococcal Conjugate Vaccine (PCV) demonstrated a statistically significant decline after chemotherapy in ALL patients (p < 0.0001). Subgroup analysis further revealed marked and heterogeneous declines in SPR after chemotherapy, with the magnitude of reduction varying significantly across vaccines—tetanus, HBV, HAV, measles, mumps, and rubella (Subgroup differences, p = 0.0037). Conclusions: This review provides an updated assessment of this critical topic, representing the first meta-analysis specifically focused on the effects of chemotherapy on different vaccines’ immunogenicity in children with ALL. Full article

(This article belongs to the Special Issue Promoting Research, Development and Access to Vaccines to Address Global Inequities)

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12 pages, 221 KiB

Open AccessArticle

Development and Preclinical Evaluation of a Lyophilized Vaccine Against Equine Herpesvirus Type 4 (EHV-4)

by Lespek Kutumbetov, Balzhan Myrzakhmetova, Aiganym Tussipova, Gulzhan Zhapparova, Talshyn Tlenchiyeva, Karina Bissenbayeva, Sergazy Nurabayev and Aslan Kerimbayev

Vaccines 2025, 13(6), 604; https://doi.org/10.3390/vaccines13060604 - 31 May 2025

Abstract

Background/Objectives: Equine rhinopneumonia, caused by equine herpesvirus types 1 and 4 (EHV-1 and EHV-4), continues to be a significant health and economic concern in the global equine industry, particularly in Kazakhstan. While vaccines targeting EHV-1 are available, there is currently no licensed monovalent [...] Read more.

Background/Objectives: Equine rhinopneumonia, caused by equine herpesvirus types 1 and 4 (EHV-1 and EHV-4), continues to be a significant health and economic concern in the global equine industry, particularly in Kazakhstan. While vaccines targeting EHV-1 are available, there is currently no licensed monovalent vaccine for EHV-4, and existing formulations offer limited protection against this serotype. This study aimed to develop and evaluate a freeze-dried, live-attenuated EHV-4 vaccine with improved safety, stability, and immunogenicity. Methods: A field isolate of EHV-4 was attenuated through serial passaging in primary lamb testicle (LT-KK49) cell cultures. Viral biomass was concentrated and formulated with various stabilizers before freeze-drying. The most effective stabilizer composition—sucrose, gelatin, and lactalbumin hydrolysate—was selected based on viral titer retention. Safety and immunogenicity were assessed in mice, guinea pigs, rabbits, donkeys, and horses. A guinea pig reproductive challenge model was used to evaluate protective efficacy. Results: The optimized lyophilized vaccine retained infectivity (>6.0 log₁₀ TCID_50/cm³) for at least six months at 4 °C. No adverse clinical signs were observed in any test species. Immunization induced robust neutralizing antibody responses in both small animals and equines. In the guinea pig model, vaccinated females demonstrated 100% pregnancy retention and fetal viability following challenge with a virulent EHV-4 strain. Conclusions: This freeze-dried, live-attenuated EHV-4 vaccine candidate is safe, immunogenic, and thermostable. It offers a promising platform for the targeted prevention of EHV-4 infection, particularly in young horses and in regions with limited cold-chain infrastructure. Full article

(This article belongs to the Section Veterinary Vaccines)

16 pages, 2725 KiB

Open AccessSystematic Review

Effects of Pneumococcal Vaccination in Children Under Five Years of Age in the Democratic Republic of Congo: A Systematic Review

by Marcellin Mengouo Nimpa, Abel Ntambue, Christian Ngandu, M. Carolina Danovaro-Holliday, André Bita Fouda, Aimé Mwana-Wabene Cikomola, Jean-Crispin Mukendi, Dieudonné Mwamba, Adèle Daleke Lisi Aluma, Moise Désiré Yapi, Jean Baptiste Nikiema, Boureima Hama Sambo and Daniel Katuashi Ishoso

Vaccines 2025, 13(6), 603; https://doi.org/10.3390/vaccines13060603 - 31 May 2025

Abstract

Background: In the Democratic Republic of Congo (DRC), the 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in 2011 through a three-dose schedule, targeting infants as part of the Expanded Program on Immunization (EPI), to reduce pneumococcal-related morbidity and mortality. The aim of this [...] Read more.

Background: In the Democratic Republic of Congo (DRC), the 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in 2011 through a three-dose schedule, targeting infants as part of the Expanded Program on Immunization (EPI), to reduce pneumococcal-related morbidity and mortality. The aim of this study was to determine the proportion of pneumonia and meningitis cases and deaths prevented in children under five following the introduction of this vaccine. Methods: This is a systematic review. We synthesized findings from studies carried out in the DRC between 2011 and 2023. We searched scientific articles, published and unpublished doctoral theses and conference proceedings. Only papers written in French or English and those reporting the results of original analytical studies were selected. We assessed the direct effect of PCV13 by calculating the proportion of infections avoided, using Odds Ratios or prevalence ratios related to infection or pneumococcal carriage. Results: Four studies were included in this review. Regarding pneumococcal carriage, when children received three PCV13 doses, the prevalence of carriage was reduced by 93.3% (95% CI: 86.3 to 96.6%), while a single dose did not significantly reduce the prevalence of carriage compared with children who had not received any dose. Concerning pneumonia prevention, three doses of PCV13 prevented 66.7% (95% CI: 37.2 to 82.2) of cases among vaccinated children. The proportion of meningitis attributable to S. pneumoniae prevented was 75.0% (95% CI: 6% to 93.3%) among children vaccinated with PCV13. S. pneumoniae serotypes 19F and 23F were the most frequent causes of invasive pneumonia in children. Serotypes 35B/35C, 15B/C, 10A and 11A/D were the most frequently identified causes of morbidity in Congolese children. In 2022, with PCV13 vaccination coverage at 79.0%, an estimated 113,359 cases of severe pneumonia and 17,255 pneumonia-related deaths were prevented in the DRC, with 3313 cases and 1544 deaths attributable to pneumococcal meningitis prevented. Conclusions: There is clear, but scattered, evidence of reduced colonization by S. pneumoniae and hospital admissions due to pneumococcal pneumonia and meningitis. The results also show that S. pneumoniae serotypes 35B/35C, 15B/C, 10A and 11A/D not included in PCV13 were the main cause of pneumococcal disease in unvaccinated or under-vaccinated children. These data support the need to continue improving vaccination coverage among children who are unvaccinated or incompletely vaccinated with PCV13 to reduce the burden of pneumococcal infections in the DRC. Full article

(This article belongs to the Special Issue Inequality in Immunization 2025)

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9 pages, 511 KiB

Open AccessBrief Report

Immunotherapeutic Blockade of CD47 Increases Virus Neutralization Antibodies

by Lamin B. Cham, Thamer A. Hamdan, Hilal Bhat, Bello Sirajo, Murtaza Ali, Khaled Saeed Tabbara, Eman Farid, Mohamed-Ridha Barbouche and Tom Adomati

Vaccines 2025, 13(6), 602; https://doi.org/10.3390/vaccines13060602 - 31 May 2025

Abstract

Background/Objectives: CD47 is a cell surface glycoprotein moderately expressed in healthy cells and upregulated in cancer and viral infected cells. CD47’s interaction with signal regulatory protein alpha (SIRPα) inhibits phagocytic cells and its interaction with thrombospondin-1 inhibits T cell response. Experimental evidence has [...] Read more.

Background/Objectives: CD47 is a cell surface glycoprotein moderately expressed in healthy cells and upregulated in cancer and viral infected cells. CD47’s interaction with signal regulatory protein alpha (SIRPα) inhibits phagocytic cells and its interaction with thrombospondin-1 inhibits T cell response. Experimental evidence has revealed that the blockade of CD47 resulted in the increased activation and function of both innate and adaptive immune cells, therefore exerting antitumoral and antiviral effects. Recent studies have shown that the combination of vaccines and immune checkpoint inhibitors could be a promising approach to increasing vaccine immunogenicity. Here, we investigated the vaccinal effect of anti-CD47 antibodies and discussed the possibilities of combining anti-CD47 treatments with vaccines. Methods: Using vesicular stomatitis virus (VSV), a widely used replication-competent vaccine vector, we evaluated the impact of the immunotherapeutic blockade of CD47 on cellular, humoral, and protective immunity. We infected C57BL/6 mice with VSV, treated them with anti-CD47 antibodies or an isotype, and evaluated the total immunoglobulin (Ig), IgG neutralizing antibodies, B cell activation, CD8+ T cell effector function, and survival of the mice. Results: We found that the treatments of anti-CD47 antibodies led to significantly increased Ig and IgG neutralizing antibody levels compared to the isotype treatment. Flow cytometric analysis of B cells revealed no difference in the number of circulating B cells; however, we observed an increased surface expression of CD80 and CD86 in B cells among anti-CD47-treated mice. Further analysis of the impact of CD47 blockade on T immunity revealed a significantly higher percentage of IFN-γ⁺ CD4 and IFN-γ⁺ CD8 T cells in anti-CD47-treated mice. Upon infecting mice with a lethal VSV dose, we observed a significantly higher survival rate among the anti-CD47-treated mice compared to control mice. Conclusions: Our results indicate that anti-CD47 treatment induces a stronger cellular and humoral immune response, leading to better protection. As such, immunotherapy by CD47 blockade in combination with vaccines could be a promising approach to improve vaccine efficacy. Full article

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

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25 pages, 2016 KiB

Open AccessReview

mRNA Vaccine Technology Beyond COVID-19

by Sola Oloruntimehin, Florence Akinyi, Michael Paul and Olumuyiwa Ariyo

Vaccines 2025, 13(6), 601; https://doi.org/10.3390/vaccines13060601 - 31 May 2025

Abstract

Background/Objectives: Since their approval in early 2020, mRNA vaccines have gained significant attention since the COVID-19 pandemic as a potential therapeutic approach to tackle several infectious diseases. This article aims to review the current state of mRNA vaccine technology and its use against [...] Read more.

Background/Objectives: Since their approval in early 2020, mRNA vaccines have gained significant attention since the COVID-19 pandemic as a potential therapeutic approach to tackle several infectious diseases. This article aims to review the current state of mRNA vaccine technology and its use against other diseases. Methods: To obtain accurate and reliable data, we carefully searched the clinicaltrial.gov and individual companies’ websites for current ongoing clinical trials reports. Also, we accessed different NCBI databases for recent articles or reports of clinical trials, innovative design of mRNA vaccines, and reviews. Results: Significant progress has been made in the design and improvement of mRNA vaccine technology. Currently, there are hundreds of ongoing clinical trials on mRNA vaccines against different cancer types, infectious diseases, and genetic and rare diseases, which showcase the advancement in this technology and their potential therapeutic advantages over traditional vaccine platforms. Finally, we predict what could be a potential future direction in designing more effective mRNA vaccines, particularly against cancer. Conclusions: The results of many of the ongoing clinical trials have shown significant positive outcomes, with many of the trials already at Phase III. Despite this outlook, however, some have been terminated or withdrawn for several reasons, some of which are not made available. This means that despite the advancement, there is a need for more research and critical evaluation of each innovation to better understand their immunological benefits and long-term effects. Full article

(This article belongs to the Section DNA and mRNA Vaccines)

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14 pages, 1489 KiB

Open AccessArticle

Orally Dissolving Film-Based Influenza Vaccines Confer Superior Protection Compared to the Oral Administration of Inactivated Influenza Virus

by Keon-Woong Yoon, Jie Mao, Gi-Deok Eom, Su In Heo, Ki Back Chu, Mi Suk Lee and Fu-Shi Quan

Vaccines 2025, 13(6), 600; https://doi.org/10.3390/vaccines13060600 - 31 May 2025

Abstract

Background: Self-administered orally dissolving films (ODFs) encapsulating inactivated influenza vaccines represent an effective strategy for stimulating mucosal immunity. While this vaccination method offers several advantages over conventional influenza vaccines, a comparative efficacy study remains lacking. Methods: Female BALB/c mice were immunized [...] Read more.

Background: Self-administered orally dissolving films (ODFs) encapsulating inactivated influenza vaccines represent an effective strategy for stimulating mucosal immunity. While this vaccination method offers several advantages over conventional influenza vaccines, a comparative efficacy study remains lacking. Methods: Female BALB/c mice were immunized with inactivated A/PR/8/34 (H1N1) either via orogastric inoculation or through the oral mucosal delivery using pullulan and trehalose-based ODF vaccines. Each group received equivalent antigen doses across three immunizations. Humoral responses and antibody functionality were assessed using sera collected post-immunization. After lethal viral challenge, other immunological and virological parameters were determined in corresponding tissues. Body weight and survival were monitored over a 14-day period after challenge. Results: ODF vaccination elicited significantly higher virus-specific IgA levels, HAI titers, and neutralizing antibody activity than oral gavage. After the viral challenge, ODF-immunized mice exhibited stronger IgG and IgA responses in respiratory tissues, increased antibody-secreting cells in lungs and spleen, and elevated germinal center B cells and CD8⁺ T cell responses. Both vaccination methods reduced lung pro-inflammatory cytokines and provided full protection against lethal challenge; however, the ODF group showed lower cytokine levels, better weight maintenance, and reduced viral loads. Conclusions: ODF vaccination elicits more robust systemic and mucosal immune responses than oral vaccination and may serve as a promising alternative method of influenza vaccine delivery. Full article

(This article belongs to the Special Issue Virus Pandemics and Vaccinations)

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19 pages, 301 KiB

Open AccessArticle

A Cross-Sectional Study to Understand HPV Vaccine Hesitancy and Influencing Factors in Italian Adults

by Marianna Riccio, Azzurra Massimi, Erika Renzi, Michele Innocenzio, Roberta Siliquini, Fabrizio Bert, Anna Odone, Carolina Marzuillo, Paolo Villari and Corrado De Vito

Vaccines 2025, 13(6), 599; https://doi.org/10.3390/vaccines13060599 - 31 May 2025

Abstract

Objectives: The Human papillomavirus (HPV) vaccine is a cornerstone of cancer prevention, yet uptake remains suboptimal in many countries. This study analyzed the factors influencing HPV vaccine acceptance among adults, including a focused analysis of parental behaviors. Methods: Data were collected through a [...] Read more.

Objectives: The Human papillomavirus (HPV) vaccine is a cornerstone of cancer prevention, yet uptake remains suboptimal in many countries. This study analyzed the factors influencing HPV vaccine acceptance among adults, including a focused analysis of parental behaviors. Methods: Data were collected through a web-based survey using a questionnaire. We performed univariable analysis and three logistic regression analyses to investigate the determinants in the overall sample and among parents. Results: A total of 1821 participants were surveyed. HPV vaccination uptake was low, with only 6.9% of the total sample and 7.6% of young adults (18–35 yo) vaccinated. Among parents, 47.9% had vaccinated children aged 12–17, and 21.1% those aged 18 and over. Higher health literacy was associated with positive attitudes (OR 2.03, 95% CI 1.48–2.79), while receiving information from pediatricians or gynecologists was linked to children’s vaccination status (OR 7.30, 95% CI 2.29–23.31) and parents’ intentions for future HPV vaccination (OR 5.86, 95% CI 1.85–18.50). Adequate knowledge emerged as a strong predictor of positive attitudes (OR 6.50, 95% CI 4.91–8.61) and parents’ intentions (OR 4.89, 95% CI 2.21–10.84). Vaccination status was a key factor influencing parental decisions and overall vaccine acceptance. Conclusions: These findings highlight the critical role of health professionals and the need for targeted communication to address persistent knowledge gaps and promote HPV vaccine confidence within general population. Full article

(This article belongs to the Section Human Papillomavirus Vaccines)

18 pages, 603 KiB

Open AccessArticle

Coverage of HPV Vaccination and Influencing Factors Among Female College Students in Northern China

by Li Yang, Chen Xing, Xue Yu, Yanrui Xu, Weibing Wang, Caiyun Chang and Qingbin Lu

Vaccines 2025, 13(6), 598; https://doi.org/10.3390/vaccines13060598 - 31 May 2025

Abstract

Background: Despite the significant global disease burden associated with HPV infection, the vaccination coverage among female college students in China remains suboptimal. This study aimed to examine HPV vaccination coverage, knowledge levels, and determinants influencing vaccination behavior among female college students in northern [...] Read more.

Background: Despite the significant global disease burden associated with HPV infection, the vaccination coverage among female college students in China remains suboptimal. This study aimed to examine HPV vaccination coverage, knowledge levels, and determinants influencing vaccination behavior among female college students in northern China, utilizing the Health Belief Model (HBM) as a theoretical framework. Methods: A cross-sectional online survey was conducted from December 2024 to January 2025, involving 4076 female students from six universities in Jinan, China. The participants were categorized into three groups: vaccinated (VG), willing-to-vaccinate (WTG), and unwilling-to-vaccinate (UTG). Data on sociodemographic characteristics, HPV knowledge, health beliefs, and vaccination behavior were analyzed using ANOVA, chi-square tests, correlation analysis, and multivariate logistic regression. Results: The vaccination rate was 18.11%, with 40.19% expressing willingness to vaccinate and 41.71% expressing unwillingness. Vaccinated students demonstrated higher levels of HPV knowledge (6.66 ± 2.67 compared to 4.76 ± 3.10 in the UTG, p < 0.001) and were predominantly from urban areas (OR = 0.64, p < 0.001). The key determinants of vaccination uptake included perceived benefits (OR = 1.54, p < 0.001), perceived barriers (OR = 3.34, p < 0.001), self-decision-making ability (OR = 1.80, p < 0.001), and social motivation (OR = 0.21, p < 0.001). Notably, increased knowledge was associated with vaccine hesitancy in the WTG group (OR = 0.45, p < 0.001), indicating that information overload may adversely affect decision-making processes. Structural barriers, such as cost (42.63%), safety concerns (46.59%), and misconceptions (e.g., 57.76% cited “no sexual activity” as a reason for refusal), significantly impeded vaccine uptake. Conclusions: The low coverage of HPV vaccination is indicative of deficiencies in knowledge, socioeconomic disparities, and cultural perceptions. Tailored interventions should focus on educational efforts to correct misconceptions, provide subsidized access to vaccines, and implement empowerment strategies that enhance self-efficacy and informed decision-making. Policymakers should incorporate these findings into national cervical cancer prevention programs to address the gap between vaccination intention and behavior among young women in China. Full article

(This article belongs to the Section Human Papillomavirus Vaccines)

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