Vaccines

26 pages, 542 KiB

Open AccessReview

Challenges to the Effectiveness and Immunogenicity of COVID-19 Vaccines: A Narrative Review with a Systematic Approach

by Alexander A. Soldatov, Nickolay A. Kryuchkov, Dmitry V. Gorenkov, Zhanna I. Avdeeva, Oxana A. Svitich and Sergey Soshnikov

Vaccines 2025, 13(8), 789; https://doi.org/10.3390/vaccines13080789 - 24 Jul 2025

Abstract

The COVID-19 pandemic accelerated the rapid development and distribution of various vaccine platforms, resulting in a significant reduction in disease severity, hospitalizations, and mortality. However, persistent challenges remain concerning the durability and breadth of vaccine-induced protection, especially in the face of emerging SARS-CoV-2 [...] Read more.

The COVID-19 pandemic accelerated the rapid development and distribution of various vaccine platforms, resulting in a significant reduction in disease severity, hospitalizations, and mortality. However, persistent challenges remain concerning the durability and breadth of vaccine-induced protection, especially in the face of emerging SARS-CoV-2 variants. This review aimed to evaluate the factors influencing the immunogenicity and effectiveness of COVID-19 vaccines to inform future vaccine advancement strategies. A narrative review with systematic approach was conducted following PRISMA guidelines for narrative review. Literature was sourced from databases including PubMed, Embase, and Web of Science for studies published between December 2019 and May 2025. Encompassed studies assessed vaccine efficacy, immunogenicity, and safety across various populations and vaccine platforms. Data were collected qualitatively, with quantitative data from reviews highlighted where available. We have uncovered a decline in vaccine efficacy over time and weakened protection against novel variants such as Delta and Omicron. Booster doses, specifically heterologous regimens, improved immunogenicity and increased protection. Vaccine-induced neutralizing antibody titers have been found to correlate with clinical protection, although the long-term correlates of immunity remain poorly defined. The induction of IgG4 antibodies after repeated mRNA vaccinations raised concerns about potential modulation of the immune response. COVID-19 vaccines have contributed significantly to pandemic control; however, their efficacy is limited by the evolution of the virus and declining immunity. Forthcoming vaccine strategies should focus on broad-spectrum, variant-adapted formulations and defining robust comparisons of protection. Recognizing the immunological basis of vaccine response, including the role of specific antibody subclasses, is fundamental for optimizing long-term protection. Full article

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

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17 pages, 5140 KiB

Open AccessArticle

Comparative Analysis of Chitosan, Lipid Nanoparticles, and Alum Adjuvants in Recombinant SARS-CoV-2 Vaccine: An Evaluation of Their Immunogenicity and Serological Efficacy

by Majed Ghattas, Garima Dwivedi, Anik Chevrier, Trevor Scobey, Rakan El-Mayta, Melissa D. Mattocks, Dong Wang, Marc Lavertu and Mohamad-Gabriel Alameh

Vaccines 2025, 13(8), 788; https://doi.org/10.3390/vaccines13080788 - 24 Jul 2025

Abstract

Background: Chitosan, a family of polysaccharides composed of glucosamine and N-acetyl glucosamine, is a promising adjuvant candidate for eliciting potent immune response. Methods: This study compared the adjuvant effects of chitosan to those of empty lipid nanoparticles (eLNPs) and aluminum hydroxide (alum) following [...] Read more.

Background: Chitosan, a family of polysaccharides composed of glucosamine and N-acetyl glucosamine, is a promising adjuvant candidate for eliciting potent immune response. Methods: This study compared the adjuvant effects of chitosan to those of empty lipid nanoparticles (eLNPs) and aluminum hydroxide (alum) following administration of recombinant SARS-CoV-2 spike immunogen in adult mice. Mice received the adjuvanted recombinant protein vaccine in a prime-boost regimen with four weeks interval. Subsequent analyses included serological assessment of antibody responses, evaluation of T cell activity, immune cell recruitment and cytokine profiles at injection site. Results: Compared to alum, chitosan induced a more balanced Th1/Th2 response, akin to that observed with eLNPs, demonstrating its ability to modulate both the humoral and cellular immune pathways. Chitosan induced a different proinflammatory cytokine (e.g., IL-1⍺, IL-2, IL-6, and IL-7) and chemokine (e.g., Eotaxin, IP-10, MIP-1a) profile compared to eLNPs and alum at the injection site and in the draining lymph nodes. Moreover, chitosan potentiated the recruitment of innate immune cells, with neutrophils accounting for about 40% of the infiltrating cells in the muscle, representing a ~10-fold increase compared to alum and a comparable level to eLNPs. Conclusions: These findings collectively indicate that chitosan has the potential to serve as an effective adjuvant, offering comparable, and potentially superior, properties to those of currently approved adjuvants. Full article

(This article belongs to the Special Issue Advances in Vaccine Adjuvants)

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12 pages, 1798 KiB

Open AccessArticle

Protective Efficacy Induced by Virus-like Particles Expressing Dense Granule Protein 5 of Toxoplasma gondii

by Su In Heo, Hae-Ji Kang, Jie Mao, Zhao-Shou Yang, Md Atique Ahmed and Fu-Shi Quan

Vaccines 2025, 13(8), 787; https://doi.org/10.3390/vaccines13080787 - 24 Jul 2025

Abstract

Background: Toxoplasma gondii (T. gondii) causes severe disease in immunocompromised individuals and pregnant women, underscoring the urgent need for effective vaccines against toxoplasmosis. The dense granule protein 5 (GRA5) of T. gondii plays a key role in parasitic cyst formation. [...] Read more.

Background: Toxoplasma gondii (T. gondii) causes severe disease in immunocompromised individuals and pregnant women, underscoring the urgent need for effective vaccines against toxoplasmosis. The dense granule protein 5 (GRA5) of T. gondii plays a key role in parasitic cyst formation. Methods: This study evaluated the protective immune responses induced by a virus-like particle (VLP) vaccine expressing the T. gondii-derived antigen GRA5 in a mouse model challenged with the ME49 strain of T. gondii. GRA5 VLPs were generated using a baculovirus expression system, and VLP formation was confirmed by Western blotting and visualized using transmission electron microscopy. Mice were intranasally immunized with GRA5 VLPs three times at 4-week intervals to induce immune responses, followed by infection with T. gondii ME49. Results: Intranasal immunization with GRA5 VLPs induced parasite-specific IgG antibody responses in the serum and both IgG and IgA antibody responses in the brain. Compared to the non-immunized group, immunized mice exhibited significantly higher levels of germinal center B cells and antibody-secreting cell responses. Moreover, the VLP vaccine suppressed the production of IFN-γ and IL-6 cytokines, leading to a significant reduction in brain inflammation and decreased cyst counts following lethal challenge with T. gondii ME49 infection. Conclusion: These findings suggest that the GRA5 VLP vaccine derived from T. gondii elicits a protective immune response, highlighting its potential as an effective vaccine candidate against toxoplasmosis. Full article

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

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18 pages, 692 KiB

Open AccessReview

Literature Review and Policy Recommendations for Single-Dose HPV Vaccination Schedule in China: Opportunities and Challenges

by Kexin Cao and Yiu-Wing Kam

Vaccines 2025, 13(8), 786; https://doi.org/10.3390/vaccines13080786 - 24 Jul 2025

Abstract

Cervical cancer remains a significant global public health challenge, with human papillomavirus (HPV) as its primary cause. In response, the World Health Organization (WHO) launched a global strategy to eliminate cervical cancer by 2030 and, in its 2022 position paper, recommended a single-dose [...] Read more.

Cervical cancer remains a significant global public health challenge, with human papillomavirus (HPV) as its primary cause. In response, the World Health Organization (WHO) launched a global strategy to eliminate cervical cancer by 2030 and, in its 2022 position paper, recommended a single-dose vaccination schedule. The objective of this review is to critically examine the current HPV vaccination landscape in China, including vaccination policies, immunization schedules, supply–demand dynamics, and the feasibility of transitioning to a single-dose regimen. By synthesizing recent developments in HPV virology, epidemiology, vaccine types, and immunization strategies, we identify both opportunities and barriers unique to the Chinese context. Results indicate that China primarily adheres to a three-dose vaccination schedule, with an optional two-dose schedule for girls aged 9–14, leaving a notable gap compared to the most recent WHO recommendation. The high prevalence of HPV types 52 and 58 contributes to a distinct regional infection pattern, underscoring the specific need for nine-valent vaccines tailored to China’s epidemiological profile. Despite the growing demand, vaccine supply remains inadequate, with an estimated annual shortfall of more than 15 million doses. This issue is further complicated by strong public preference for the nine-valent vaccine and the relatively high cost of vaccination. Emerging evidence supports the comparable efficacy and durable protection of a single-dose schedule, which could substantially reduce financial and logistical burdens while expanding coverage. This review advocates for the adoption of a simplified single-dose regimen, supported by catch-up strategies for older cohorts and the integration of HPV vaccination into China’s National Immunization Program (NIP). Sustained investment in domestic vaccine development and centralized procurement of imported vaccines may also possibly alleviate supply shortage. These coordinated efforts are critical for strengthening HPV-related disease prevention and accelerating China’s progress toward the WHO’s cervical cancer elimination targets. Full article

(This article belongs to the Special Issue Vaccination Strategies for Global Public Health)

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21 pages, 1292 KiB

Open AccessArticle

Polymorphism in IFNλ Can Impact the Immune/Inflammatory Response to COVID-19 Vaccination in Older CMV-Seropositive Adults

by Ariane Nardy, Fernanda Rodrigues Monteiro, Brenda Rodrigues Silva, Jônatas Bussador do Amaral, Danielle Bruna Leal Oliveira, Érika Donizetti de Oliveira Cândido, Edison Luiz Durigon, Andressa Simões Aguiar, Guilherme Pereira Scagion, Vanessa Nascimento Chalup, Guilherme Eustáquio Furtado, Marina Tiemi Shio, Carolina Nunes França, Luiz Henrique da Silva Nali and André Luis Lacerda Bachi

Vaccines 2025, 13(8), 785; https://doi.org/10.3390/vaccines13080785 - 24 Jul 2025

Abstract

Background: Chronic cytomegalovirus (CMV) infection may favor the development of immunosenescence and inflammation that impair vaccine responses, including COVID-19. In addition, the polymorphism of the interferon-lambda gene (IFNλ) affects COVID-19 immune responses in older adults. Objective: We aimed to investigate the impact of [...] Read more.

Background: Chronic cytomegalovirus (CMV) infection may favor the development of immunosenescence and inflammation that impair vaccine responses, including COVID-19. In addition, the polymorphism of the interferon-lambda gene (IFNλ) affects COVID-19 immune responses in older adults. Objective: We aimed to investigate the impact of IFNλ polymorphism (IL28B gene-rs12979860) on the immune/inflammatory response to vaccination with CoronaVac for COVID-19 in older adults who were CMV-seropositive. Methods: Blood samples from 42 CMV-seropositive older adults (73.7 ± 4.5 years) were collected before and 30 days after immunization with a second dose of the CoronaVac vaccine to evaluate the immune/inflammatory response. Results: At genotyping, 20 subjects were homozygous for the C/C alleles (Allele-1 group), 5 were homozygous for the T/T Alleles (Allele-2 group), and 17 were heterozygous (C/T, Alleles-1/2 group). The Allele-1 group showed higher IgG levels for COVID-19 (p = 0.0269) and intermediate monocyte percentage (p = 0.017), in contrast to a lower non-classical monocyte percentage (p = 0.0141) post-vaccination than pre-vaccination. Also, this group showed that IgG levels for CMV were positively associated with a systemic pro-inflammatory state and senescent T cells (CD4+ and CD8+). The Allele-2 group presented higher IFN-β levels at pre- (p = 0.0248) and post-vaccination (p = 0.0206) than the values in the Allele-1 and Alleles-1/2 groups, respectively. In addition, the Allele-2 and Alleles-1/2 groups showed that IgG levels for COVID-19 were positively associated with a balanced systemic inflammatory state. Conclusion: CMV-seropositivity in older adults who had Allele-1 could lead to an unbalanced systemic inflammatory state, which may impair their antibody response to COVID-19 vaccination compared to other volunteer groups. Full article

(This article belongs to the Special Issue Vaccine-Induced Humoral Immunity: Mechanisms of Induction and Idiotypic Network Interactions)

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22 pages, 1419 KiB

Open AccessReview

A Narrative Review of College Meningococcal Vaccination Mandates Across the United States

by Jessica Presa, Eva Jodar, Monica Ochapa, Tim A. Mullenix, Sharon E. Barrett and Alejandro Cane

Vaccines 2025, 13(8), 784; https://doi.org/10.3390/vaccines13080784 - 24 Jul 2025

Abstract

In the United States, adolescents and young adults between the ages of 16 and 23 have high rates of serogroup B meningococcal infections due to an elevated risk for those attending college. This review examines meningococcal vaccination requirements and recommendations for college students [...] Read more.

In the United States, adolescents and young adults between the ages of 16 and 23 have high rates of serogroup B meningococcal infections due to an elevated risk for those attending college. This review examines meningococcal vaccination requirements and recommendations for college students in the United States, with a focus on state-level mandates. National stakeholder resources, state legislatures, and official state Department of Health and Department of Education websites were analyzed for each state and Washington, DC. Overall, 26 states mandate MenACWY vaccination for college entry, whereas only 2 have specific requirements for MenB vaccination. Among the six states with the largest state university campus enrollments, half mandate MenACWY vaccination for college students, whereas none mandate MenB. By region, the Northeast had the highest percentage of states with a MenACWY requirement for college entry (77.8%) followed by the South (64.7%), Midwest (41.7%), and West (23.1%). Further research is needed to elucidate the relationship between state mandates and coverage to aid in optimizing meningococcal vaccination for college students. Full article

(This article belongs to the Section Epidemiology and Vaccination)

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15 pages, 2688 KiB

Open AccessArticle

Recombinant Tetrameric Neuraminidase Subunit Vaccine Provides Protection Against Swine Influenza A Virus Infection in Pigs

by Ao Zhang, Bin Tan, Jiahui Wang and Shuqin Zhang

Vaccines 2025, 13(8), 783; https://doi.org/10.3390/vaccines13080783 - 23 Jul 2025

Abstract

Background/Objectives: Swine influenza A virus (swIAV), a prevalent respiratory pathogen in porcine populations, poses substantial economic losses to global livestock industries and represents a potential threat to public health security. Neuraminidase (NA) has been proposed as an important component for universal influenza [...] Read more.

Background/Objectives: Swine influenza A virus (swIAV), a prevalent respiratory pathogen in porcine populations, poses substantial economic losses to global livestock industries and represents a potential threat to public health security. Neuraminidase (NA) has been proposed as an important component for universal influenza vaccine development. NA has potential advantages as a vaccine antigen in providing cross-protection, with specific antibodies that have a broad binding capacity for heterologous viruses. In this study, we evaluated the immunogenicity and protective efficacy of a tetrameric recombinant NA subunit vaccine in a swine model. Methods: We constructed and expressed structurally stable soluble tetrameric recombinant NA (rNA) and prepared subunit vaccines by mixing with ISA 201 VG adjuvant. The protective efficacy of rNA-ISA 201 VG was compared to that of a commercial whole inactivated virus vaccine. Pigs received a prime-boost immunization (14-day interval) followed by homologous viral challenge 14 days post-boost. Results: Both rNA-ISA 201 VG and commercial vaccine stimulated robust humoral responses. Notably, the commercial vaccine group exhibited high viral-binding antibody titers but very weak NA-specific antibodies, whereas rNA-ISA 201 VG immunization elicited high NA-specific antibody titers alongside substantial viral-binding antibodies. Post-challenge, both immunization with rNA-ISA 201 VG and the commercial vaccine were effective in inhibiting viral replication, reducing viral load in porcine respiratory tissues, and effectively mitigating virus-induced histopathological damage, as compared to the PBS negative control. Conclusions: These findings found that the anti-NA immune response generated by rNA-ISA 201 VG vaccination provided protection comparable to that of a commercial inactivated vaccine that primarily induces an anti-HA response. Given that the data are derived from one pig per group, there is a requisite to increase the sample size for more in-depth validation. This work establishes a novel strategy for developing next-generation SIV subunit vaccines leveraging NA as a key immunogen. Full article

(This article belongs to the Special Issue Vaccine Development for Swine Viral Pathogens)

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11 pages, 242 KiB

Open AccessReview

Varicella-Zoster Virus Infection and Varicella-Zoster Virus Vaccine-Related Ocular Complications

by Jing Yu, Huihui Li, Yuying Ji and Hailan Liao

Vaccines 2025, 13(8), 782; https://doi.org/10.3390/vaccines13080782 - 23 Jul 2025

Abstract

The varicella-zoster virus is a human herpesvirus that causes varicella as the primary infection and HZ as the reactivation of a latent infection. Ten to twenty percent of cases of herpes zoster ophthalmicus (HZO) involve the ophthalmic branch of the fifth cranial nerve. [...] Read more.

The varicella-zoster virus is a human herpesvirus that causes varicella as the primary infection and HZ as the reactivation of a latent infection. Ten to twenty percent of cases of herpes zoster ophthalmicus (HZO) involve the ophthalmic branch of the fifth cranial nerve. Any area of the eye may be affected by the condition. HZ has a lifetime risk of more than 30%. Complications from herpes zoster can significantly lower quality of life. The goal of HZ vaccinations is to stop HZ activation and PHN formation. Despite the uncommon possibility of side effects such as eye problems, the majority of vaccines on the market now are safe. The purpose of this review is to discuss VZV infection and analyze and summarize the ocular complications following VZV vaccination. Full article

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

18 pages, 4044 KiB

Open AccessArticle

Preparation and Immunogenicity Evaluation of a Ferritin-Based GnRH Nanoparticle Vaccine

by Ying Xu, Weihao Zhao, Yuhan Zhu, Bo Sun, Congmei Wu and Yuhe Yin

Vaccines 2025, 13(8), 781; https://doi.org/10.3390/vaccines13080781 - 23 Jul 2025

Abstract

Objectives: Research on the immunocastration vaccine is of great significance for animal management. In this study, the gonadotropin-releasing hormone (GnRH) ferritin nanoparticle vaccine was constructed using Spy Catcher-Spy Tag (SC-ST) as a delivery system; Methods: The Spy Catcher was constructed to [...] Read more.

Objectives: Research on the immunocastration vaccine is of great significance for animal management. In this study, the gonadotropin-releasing hormone (GnRH) ferritin nanoparticle vaccine was constructed using Spy Catcher-Spy Tag (SC-ST) as a delivery system; Methods: The Spy Catcher was constructed to fuse with the expression vector pET-30a-SF of ferritin nanoparticles. Two polypeptides, STG1: Spy Tag-GnRH I-PADRE and STG2: Spy Tag-GnRH I-GnRH II, coupled to SF in vitro to form two nanoparticles, were designed and synthesized to detect castration effects in mice. We mixed them with the adjuvant MONTANIDE ISA 206 VG to explore the adjuvant’s effect on immunogenicity; Results: All immunized groups produced anti-GnRH specific antibodies after the second immunization, which was significantly higher in the immunized group and the combined adjuvant group than in the control group, and the immune response could still be detected at the 12th week. The concentrations of testosterone, follicle-stimulating hormone, and luteinizing hormone in serum were significantly decreased. The number of sperm in the epididymis of mice in each immune group was significantly reduced, and the rate of sperm deformity was high; Conclusions: The two ferritin-based GnRH nanoparticles developed in this study can significantly cause testicular atrophy, decreased gonadal hormone concentration, decreased sperm count, and increased deformity rate in male mice. These findings provide experimental evidence supporting their potential application in animal immunocastration. Full article

(This article belongs to the Section Veterinary Vaccines)

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21 pages, 3103 KiB

Open AccessArticle

Systemic and Mucosal Humoral Immune Responses to Lumazine Synthase 60-mer Nanoparticle SARS-CoV-2 Vaccines

by Cheng Cheng, Jeffrey C. Boyington, Edward K. Sarfo, Cuiping Liu, Danealle K. Parchment, Andrea Biju, Angela R. Corrigan, Lingshu Wang, Wei Shi, Yi Zhang, Yaroslav Tsybovsky, Tyler Stephens, Adam S. Olia, Audrey S. Carson, Syed M. Moin, Eun Sung Yang, Baoshan Zhang, Wing-Pui Kong, Peter D. Kwong, John R. Mascola and Theodore C. Pierson Show full author list Hide full author list

Vaccines 2025, 13(8), 780; https://doi.org/10.3390/vaccines13080780 - 23 Jul 2025

Abstract

Background: Vaccines that stimulate systemic and mucosal immunity to a level required to prevent SARS-CoV-2 infection and transmission are an unmet need. Highly protective hepatitis B and human papillomavirus nanoparticle vaccines highlight the potential of multivalent nanoparticle vaccine platforms to provide enhanced immunity. [...] Read more.

Background: Vaccines that stimulate systemic and mucosal immunity to a level required to prevent SARS-CoV-2 infection and transmission are an unmet need. Highly protective hepatitis B and human papillomavirus nanoparticle vaccines highlight the potential of multivalent nanoparticle vaccine platforms to provide enhanced immunity. Here, we report the construction and characterization of self-assembling 60-subunit icosahedral nanoparticle SARS-CoV-2 vaccines using the bacterial enzyme lumazine synthase (LuS). Methods and Results: Nanoparticles displaying prefusion-stabilized SARS-CoV-2 spike ectodomains fused to the surface-exposed amino terminus of LuS were designed using structure-guided approaches. Negative stain-electron microscopy studies of purified nanoparticles were consistent with self assembly into 60-mer nanoparticles displaying 20 spike trimers. After two intramuscular doses, these purified spike-LuS nanoparticles elicited significantly higher SARS-CoV-2 neutralizing activity than spike trimers in vaccinated mice. Furthermore, intramuscular DNA priming and intranasal boosting with a SARS-CoV-2 LuS nanoparticle vaccine stimulated mucosal IgA responses. Conclusion: These data identify LuS nanoparticles as highly immunogenic SARS-CoV-2 vaccine candidates and support the further development of this platform against SARS-CoV-2 and its emerging variants. Full article

(This article belongs to the Special Issue Novel Vaccines and Vaccine Technologies for Emerging Infections)

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14 pages, 1713 KiB

Open AccessArticle

Survey on Awareness and Attitudes Toward Maternal Immunization Against Influenza, Pertussis, Respiratory Syncytial Virus, and Group B Streptococcus Among Pregnant Women in Japan

by Kazuya Hiiragi, Soichiro Obata, Masafumi Yamamoto, Mai Shimura, Chika Akamatsu, Azusa Tochio, Mayumi Hagiwara, Aya Mochimaru, Ai Kiyose, Miki Tanoshima, Etsuko Miyagi and Shigeru Aoki

Vaccines 2025, 13(8), 779; https://doi.org/10.3390/vaccines13080779 - 23 Jul 2025

Abstract

Background/Objective: Maternal immunization is highly recommended, particularly in developed countries. However, its awareness among pregnant women in Japan remains low. This study aimed to assess the awareness and attitudes toward maternal immunization among pregnant women in Japan and to identify the factors [...] Read more.

Background/Objective: Maternal immunization is highly recommended, particularly in developed countries. However, its awareness among pregnant women in Japan remains low. This study aimed to assess the awareness and attitudes toward maternal immunization among pregnant women in Japan and to identify the factors that may promote its acceptance. Methods: We conducted a cross-sectional questionnaire survey among pregnant women attending antenatal checkups at nine facilities in Kanagawa Prefecture, Japan, from August 2024 to January 2025. The survey assessed knowledge and intention regarding maternal immunization for influenza, pertussis, respiratory syncytial virus (RSV), and group B streptococcus (GBS) as well as attitudes toward vaccination costs and information sources. Results: Overall, 523 respondents were included in this study. The overall awareness of maternal immunization was 16%. Willingness to receive vaccinations during pregnancy was reported for influenza (68%), pertussis (58%), RSV (59%), and GBS (71%). A common reason for vaccine hesitancy included uncertainty about its effects on the fetus. The key factors associated with vaccine acceptance were higher educational attainment and prior knowledge of maternal immunization. Regarding costs, most respondents were willing to pay up to JPY 5000 (approximately USD 35). The most frequently prioritized sources were explanations from physicians, followed by explanations from midwives. Conclusions: Despite low awareness, vaccination intention was comparable to that reported in other countries. Points that may contribute to improved vaccine uptake were also identified. These findings may lead to the prevention of infectious diseases in newborns and infants in Japan and possibly improve public health. Full article

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21 pages, 3415 KiB

Open AccessArticle

SARS-CoV-2 RBD Scaffolded by AP205 or TIP60 Nanoparticles and Delivered as mRNA Elicits Robust Neutralizing Antibody Responses

by Johnathan D. Guest, Yi Zhang, Daniel Flores, Emily Atkins, Kuishu Ren, Yingyun Cai, Kim Rosenthal, Zimeng Wang, Kihwan Kim, Charles Chen, Richard Roque, Bei Cheng, Marianna Yanez Arteta, Liping Zhou, Jason Laliberte and Joseph R. Francica

Vaccines 2025, 13(8), 778; https://doi.org/10.3390/vaccines13080778 - 22 Jul 2025

Abstract

Background/Objectives: SARS-CoV-2 vaccine candidates comprising the receptor binding domain (RBD) of the spike protein have been shown to confer protection against infection. Previous research evaluating vaccine candidates with SARS-CoV-2 RBD fused to ferritin (RBD-ferritin) and other scaffolds suggested that multimeric assemblies of RBD [...] Read more.

Background/Objectives: SARS-CoV-2 vaccine candidates comprising the receptor binding domain (RBD) of the spike protein have been shown to confer protection against infection. Previous research evaluating vaccine candidates with SARS-CoV-2 RBD fused to ferritin (RBD-ferritin) and other scaffolds suggested that multimeric assemblies of RBD can enhance antigen presentation to improve the potency and breadth of immune responses. Though RBDs directly fused to a self-assembling scaffold can be delivered as messenger RNA (mRNA) formulated with lipid nanoparticles (LNPs), reports of SARS-CoV-2 vaccine candidates that combine these approaches remain scarce. Methods: Here, we designed RBD fused to AP205 or TIP60 self-assembling nanoparticles following a search of available structures focused on several scaffold properties. RBD-AP205 and RBD-TIP60 were tested for antigenicity following transfection and for immunogenicity and neutralization potency when delivered as mRNA in mice, with RBD-ferritin as a direct comparator. Results: All scaffolded RBD constructs were readily secreted to transfection supernatant and showed antigenicity in ELISA, though clear heterogeneity in assembly was observed. RBD-AP205 and RBD-TIP60 also exhibited robust antibody binding and neutralization titers in mice that were comparable to those elicited by RBD-ferritin or a full-length membrane-bound spike. Conclusions: These data suggest that AP205 and TIP60 can present RBD as effectively as ferritin and induce similar immune responses. By describing additional scaffolds for multimeric display that accommodate mRNA delivery platforms, this work can provide new tools for future vaccine design efforts. Full article

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

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15 pages, 1304 KiB

Open AccessArticle

Correlates of SARS-CoV-2 Breakthrough Infections in Kidney Transplant Recipients Following a Third SARS-CoV-2 mRNA Vaccine Dose

by Miriam Viktov Thygesen, Charlotte Strandhave, Jeanette Mølgaard Kiib, Randi Berg, Malene Söth Andersen, Emma Berggren Dall, Bodil Gade Hornstrup, Hans Christian Østergaard, Frank Holden Mose, Jon Waarst Gregersen, Søren Jensen-Fangel, Jesper Nørgaard Bech, Henrik Birn, Marianne Kragh Thomsen and Rasmus Offersen

Vaccines 2025, 13(8), 777; https://doi.org/10.3390/vaccines13080777 - 22 Jul 2025

Abstract

Background: Kidney transplant recipients (KTRs) exhibit a significantly diminished immune response to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) vaccines compared with the general population, primarily due to ongoing immunosuppressive therapy. This study evaluated the immunogenicity of a third SARS-CoV-2 mRNA vaccine dose in [...] Read more.

Background: Kidney transplant recipients (KTRs) exhibit a significantly diminished immune response to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) vaccines compared with the general population, primarily due to ongoing immunosuppressive therapy. This study evaluated the immunogenicity of a third SARS-CoV-2 mRNA vaccine dose in KTRs and assessed the association between antibody response and protection against SARS-CoV-2 breakthrough infection. Additionally, the clinical and immunological correlates of post-vaccination SARS-CoV-2 infection were examined. Methods: A prospective cohort of 135 KTRs received a third vaccine dose approximately six months following the second dose. Plasma samples were collected at baseline (pre-vaccination), six months after the second dose, and six weeks following the third dose. Humoral responses were assessed using SARS-CoV-2-specific Immunoglobulin G (IgG) titers and virus neutralization assays against wild-type (WT) and viral strains, including multiple Omicron sub-lineages. Results: After the third vaccine dose, 74% of the KTRs had detectable SARS-CoV-2-specific IgG antibodies, compared with 48% following the second dose. The mean IgG titers increased approximately ten-fold post-booster. Despite this increase, neutralizing activity against the Omicron variants remained significantly lower than that against the WT strain. KTRs who subsequently experienced a SARS-CoV-2 breakthrough infection demonstrated reduced neutralizing antibody activity across all variants tested. Additionally, individuals receiving triple immunosuppressive therapy had a significantly higher risk of SARS-CoV-2 breakthrough infection compared with those on dual or monotherapy. A multivariate machine learning analysis identified age and neutralizing activity against WT, Delta, and Omicron BA.2 as the most robust correlates of SARS-CoV-2 breakthrough infection. Conclusions: A third SARS-CoV-2 mRNA vaccine dose significantly improves SARS-CoV-2-specific IgG levels in KTRs; however, the neutralizing response against Omicron variants remains suboptimal. Diminished neutralizing capacity and intensified immunosuppression are key determinants of SARS-CoV-2 breakthrough infection in this immunocompromised population. Full article

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

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11 pages, 1605 KiB

Open AccessArticle

Year-Long Antibody Response to the EuCorVac-19 SARS-CoV-2 Vaccine in Healthy Filipinos

by Jonathan F. Lovell, Kazutoyo Miura, Yeong Ok Baik, Chankyu Lee, YoungJin Choi, Jeong-Yoon Lee, Carole A. Long, Michelle Ylade, Roxas Lee-Llacer, Norman De Asis, Mitzi Trinidad-Aseron, Jose Manuel Ranola, Loreta Zoleta De Jesus and Howard Her

Vaccines 2025, 13(8), 776; https://doi.org/10.3390/vaccines13080776 - 22 Jul 2025

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Abstract

Background: We previously reported an interim safety and immunogenicity analysis of a Phase 3 trial in the Philippines of the EuCorVac-19 (ECV-19) COVID-19 vaccine with the COVISHIELD^TM (CS) comparator (ClinicalTrials.gov identifier NCT05572879). Here, we present full-year humoral immunogenicity analysis. Methods: [...] Read more.

Background: We previously reported an interim safety and immunogenicity analysis of a Phase 3 trial in the Philippines of the EuCorVac-19 (ECV-19) COVID-19 vaccine with the COVISHIELD^TM (CS) comparator (ClinicalTrials.gov identifier NCT05572879). Here, we present full-year humoral immunogenicity analysis. Methods: Healthy adults over 18 years of age received two injections of ECV-19 or CS vaccines, with 4 weeks between prime and boost. Analysis was carried out in individuals with immunogenicity measurements available at all 4 timepoints (weeks 0, 6, 30, and 56; n = 535 for ECV-19 and n = 260 for CS). Results: 2 weeks after boosting (week 6), ECV-19 elicited higher median anti-RBD IgG (1512 vs. 340 BAU/mL, p < 0.001) and neutralizing antibodies (1280 vs. 453 median microneutralization (MN) titer, p < 0.001) compared to CS. Anti-RBD IgG remained higher for ECV-19 compared to CS through week 30 (412 vs. 238 BAU/mL, p < 0.001) and 56 (425 vs. 260 BAU/mL, p < 0.001). MN titers remained higher for ECV-19 compared to CS through week 30 (640 vs. 453, p < 0.001) and 56 (453 vs. 320, p < 0.001). Correlation between anti-RBD IgG and neutralization titers persisted throughout the study. Women generally exhibited greater antibody responses than men. In the first six months following immunization, the ECV-19 group had a median antibody half-life of 80 days for anti-RBD IgG and 112 days for MN titer. In the subsequent six months, antibody half-life increased to 237 days for anti-RBD IgG and 168 days for MN titer. Conclusions: Following initial prime-boost vaccination, ECV-19 maintained higher anti-RBD IgG and neutralizing antibody titers relative to the CS comparator over a full-year period. Full article

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

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Vaccines, Volume 13, Issue 8 (August 2025) – 14 articles

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