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Vaccines
Volume 13
Issue 1
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Vaccines, Volume 13, Issue 1 (January 2025) – 96 articles

Cover Story (view full-size image): Norovirus (NoV) protruding (P) domains that bind to receptors self-assemble into a 24-meric nanoparticle (P24 NP). By inserting the receptor-binding αTSR domain of the circumsporozoite protein of Plasmodium sporozoite into a surface loop of the P domain, we generated a self-assembling, chimeric P24-αTSR NP. The structural model, the P24-αTSR NP, was constructed, indicating that each P24-αTSR NP consists of a P24 NP core with 24 surface-exposed αTSR domains that retained authentic conformation and receptor binding function. The P24-αTSR NP elicited high antibody titers in mice toward both the NoV P domain and the αTSR domain of Plasmodium. The resulting antibodies bind to Plasmodium sporozoites and block NoV VLP binding to its receptors. Thus, the P24-αTSR NP may serve as a combination vaccine against both NoV and Plasmodium parasites. View this paper
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16 pages, 1898 KiB  
Article
Impact of HPV Catch-Up Vaccination on High-Grade Cervical Lesions (CIN2+) Among Women Aged 26–30 in Northern Norway
by Amanda Sørensen Jørgensen, Gunnar Skov Simonsen and Sveinung Wergeland Sørbye
Vaccines 2025, 13(1), 96; https://doi.org/10.3390/vaccines13010096 - 20 Jan 2025
Viewed by 782
Abstract
Background/Objectives: Human papillomavirus (HPV) is the primary cause of high-grade cervical lesions and cervical cancer worldwide. In Norway, HPV vaccination was introduced in 2009 for seventh-grade girls and extended through a catch-up program from 2016 to 2019 for women born between 1991 and [...] Read more.
Background/Objectives: Human papillomavirus (HPV) is the primary cause of high-grade cervical lesions and cervical cancer worldwide. In Norway, HPV vaccination was introduced in 2009 for seventh-grade girls and extended through a catch-up program from 2016 to 2019 for women born between 1991 and 1996. This study evaluates the impact of the catch-up vaccination program on the incidence of HPV and high-grade cervical lesions in Troms and Finnmark. Methods: We analyzed data from 40,617 women aged 26 to 30 who underwent cervical screening between 2009 and 2023 in Troms and Finnmark, including 1850 women with high-grade cervical lesions (CIN2+) on biopsy. Using linear regression, we assessed trends in high-grade lesion incidence per 1000 screened women and the association between vaccination status and HPV-16/18 incidence. Results: Between 2017 and 2023, the incidence of high-grade cervical lesions significantly decreased: CIN2+ decreased by 33.4%, and CIN3+ decreased by 63.4%. Significant reductions in HPV-16/18-associated high-grade cervical lesions were observed among vaccinated women, with the proportion of CIN2+ cases due to HPV-16 and 18 decreasing from 56.8% in 2017 to 40.7% in 2023, reflecting a 55.8% reduction in the absolute number of cases caused by these high-risk HPV types. Comparing unvaccinated women aged 25–26 in 2016 and vaccinated women in 2023, HPV-16 incidence decreased from 5.1% to 0.1%, and HPV-18 incidence decreased from 3.3% to 0.0%. Conclusions: The catch-up vaccination program significantly reduced the incidence of HPV-16/18 and high-grade cervical lesions in Troms and Finnmark, even with the lower vaccination coverage observed in the catch-up program. These findings demonstrate the effectiveness of HPV vaccination programs in reducing HPV infections and associated cervical lesions. Full article
(This article belongs to the Special Issue Human Papillomavirus Vaccine Against Cervical Cancer: New Usage Strategies and Coverage Issues)
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19 pages, 8275 KiB  
Article
Adenoviral Vector-Based Vaccine Expressing Hemagglutinin Stem Region with Autophagy-Inducing Peptide Confers Cross-Protection Against Group 1 and 2 Influenza A Viruses
by Wen-Chien Wang, Ekramy E. Sayedahmed, Marwa Alhashimi, Ahmed Elkashif, Vivek Gairola, Muralimanohara S. T. Murala, Suryaprakash Sambhara and Suresh K. Mittal
Vaccines 2025, 13(1), 95; https://doi.org/10.3390/vaccines13010095 - 20 Jan 2025
Viewed by 745
Abstract
Background/Objectives: An effective universal influenza vaccine is urgently needed to overcome the limitations of current seasonal influenza vaccines, which are ineffective against mismatched strains and unable to protect against pandemic influenza. Methods: In this study, bovine and human adenoviral vector-based vaccine platforms were [...] Read more.
Background/Objectives: An effective universal influenza vaccine is urgently needed to overcome the limitations of current seasonal influenza vaccines, which are ineffective against mismatched strains and unable to protect against pandemic influenza. Methods: In this study, bovine and human adenoviral vector-based vaccine platforms were utilized to express various combinations of antigens. These included the H5N1 hemagglutinin (HA) stem region or HA2, the extracellular domain of matrix protein 2 of influenza A virus, HA signal peptide (SP), trimerization domain, excretory peptide, and the autophagy-inducing peptide C5 (AIP-C5). The goal was to identify the optimal combination for enhanced immune responses and cross-protection. Mice were immunized using a prime-boost strategy with heterologous adenoviral (Ad) vectors. Results: The heterologous Ad vectors induced robust HA stem-specific humoral and cellular immune responses in the immunized mice. Among the tested combinations, Ad vectors expressing SP + HA stem + AIP-C5 conferred significant protection against group 1 (H1N1 and H5N1) and group 2 (H3N2) influenza A viruses. This protection was demonstrated by lower lung viral titers and reduced morbidity and mortality. Conclusions: The findings support further investigation of heterologous Ad vaccine platforms expressing SP + HA stem + AIP-C5. This combination shows promise as a potential universal influenza vaccine, providing broader protection against influenza A viruses. Full article
(This article belongs to the Special Issue Advances in Vaccines against Infectious Diseases)
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21 pages, 8315 KiB  
Article
Enhancing DNA Vaccine Delivery Through Stearyl-Modified Cell-Penetrating Peptides: Improved Antigen Expression and Immune Response In Vitro and In Vivo
by Sheng Jiang, Cheng Zu, Bin Wang and Yiwei Zhong
Vaccines 2025, 13(1), 94; https://doi.org/10.3390/vaccines13010094 - 20 Jan 2025
Viewed by 463
Abstract
Background: Inefficient cellular uptake is a significant limitation to the efficacy of DNA vaccines. In this study, we introduce S-Cr9T, a stearyl-modified cell-penetrating peptide (CPP) designed to enhance DNA vaccine delivery by forming stable complexes with plasmid DNA, thereby protecting it from degradation [...] Read more.
Background: Inefficient cellular uptake is a significant limitation to the efficacy of DNA vaccines. In this study, we introduce S-Cr9T, a stearyl-modified cell-penetrating peptide (CPP) designed to enhance DNA vaccine delivery by forming stable complexes with plasmid DNA, thereby protecting it from degradation and promoting efficient intracellular uptake. Methods and Results: In vitro studies showed that S-Cr9T significantly improved plasmid stability and transfection efficiency, with optimal performance at an N/P ratio of 0.25. High-content imaging revealed that the S-Cr9T–plasmid complex stably adhered to the cell membrane, leading to enhanced plasmid uptake and transfection. In vivo, S-Cr9T significantly increased antigen expression and triggered a robust immune response, including a threefold increase in IFN-γ secretion and several hundred-fold increases in antibody levels compared to control groups. Conclusions: These findings underscore the potential of S-Cr9T to enhance DNA vaccine efficacy, offering a promising platform for advanced gene therapy and vaccination strategies. Full article
(This article belongs to the Special Issue Innovations in Vaccine Technology)
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13 pages, 4821 KiB  
Article
Robust and Long-Lasting Immunity and Protection in Mice Induced by Lipopolyplex-Delivered mRNA Vaccines Expressing the Prefusion Protein of Respiratory Syncytial Virus
by Xuchang Shan, Ruiwen Han, Xueting Cheng, Jialuo Bing, Zhenyong Qi, Shucai Sun, Tangqi Wang, Qiaohong Chu, Yao Deng, Desheng Zhai and Wenjie Tan
Vaccines 2025, 13(1), 93; https://doi.org/10.3390/vaccines13010093 - 20 Jan 2025
Viewed by 639
Abstract
Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants and children. mRNA vaccines based on the lipopolyplex (LPP) platform have been previously reported, but they remain unapplied in RSV vaccine development. In this study, we developed a [...] Read more.
Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants and children. mRNA vaccines based on the lipopolyplex (LPP) platform have been previously reported, but they remain unapplied in RSV vaccine development. In this study, we developed a novel LPP-delivered mRNA vaccine that expresses the respiratory syncytial virus prefusion protein (RSV pre-F) to evaluate its immunogenicity and protective effect in a mouse model. We synthesized mRNAs with gene modification for RSV pre-F and prepared mRNA vaccines using the LPP delivery platform, referred to as RSV pre-F LPP-mRNA. RSV pre-F protein expression in mRNA vaccines was characterized in vitro. Then, we evaluated the effects of the immune response and protection of this mRNA vaccine in mice up to 24 weeks post-vaccination. Following booster immunization, robust and long-lasting RSV pre-F-specific IgG antibodies were detected in the serum of mice, which exhibited Th1/Th2 balanced IgG response and cross-neutralizing antibodies against different subtypes (RSV A2, B18537, and clinical isolate hRSV/C-Tan/BJ 202301), with a clear dose–response relationship observed. RSV pre-F-specific IgG antibodies were maintained in the mice for an extended period, lasting up to 18 weeks post-immunization. Concurrently, multifunctional RSV F-specific CD8+ T cells (IFN–γ, IL-2, and TNF-α) were detected in the mice. After RSV A2 challenge, the RSV pre-F LPP-mRNA vaccine led to a significant reduction in viral replication, while reduced pathological damage was observed in lung tissue. The LPP-delivered mRNA vaccine expressing RSV pre-F induces a robust and long-lasting immune response and protection, indicating good prospects for further development and application. Full article
(This article belongs to the Special Issue Research on Immune Response and Vaccines: 2nd Edition)
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27 pages, 811 KiB  
Review
Advancing the Fight Against Cervical Cancer: The Promise of Therapeutic HPV Vaccines
by Qian Zheng, Misi He, Zejia Mao, Yue Huang, Xiuying Li, Ling Long, Mingfang Guo and Dongling Zou
Vaccines 2025, 13(1), 92; https://doi.org/10.3390/vaccines13010092 - 19 Jan 2025
Viewed by 853
Abstract
Human papillomavirus (HPV) is a major global health issue and is recognized as the leading cause of cervical cancer. While prophylactic vaccination programs have led to substantial reductions in both HPV infection rates and cervical cancer incidence, considerable burdens of HPV-related diseases persist, [...] Read more.
Human papillomavirus (HPV) is a major global health issue and is recognized as the leading cause of cervical cancer. While prophylactic vaccination programs have led to substantial reductions in both HPV infection rates and cervical cancer incidence, considerable burdens of HPV-related diseases persist, particularly in developing countries with inadequate vaccine coverage and uptake. The development of therapeutic vaccines for HPV represents an emerging strategy that has the potential to bolster the fight against cervical cancer. Unlike current prophylactic vaccines designed to prevent new infections, therapeutic vaccines aim to eradicate or treat existing HPV infections, as well as HPV-associated precancers and cancers. This review focuses on clinical studies involving therapeutic HPV vaccines for cervical cancer, specifically in three key areas: the treatment of cervical intraepithelial neoplasia; the treatment of cervical cancer in combination with or without chemotherapy, radiotherapy, or immune checkpoint inhibitors; and the role of prophylaxis following completion of treatment. Currently, there are no approved therapeutic HPV vaccines worldwide; however, active progress is being made in clinical research and development using multiple platforms such as peptides, proteins, DNA, RNA, bacterial vectors, viral vectors, and cell-based, each offering relative advantages and limitations for delivering HPV antigens and generating targeted immune responses. We outline preferred vaccine parameters, including indications, target populations, safety considerations, efficacy considerations, and immunization strategies. Lastly, we emphasize that therapeutic vaccines for HPV that are currently under development could be an important new tool in fighting against cervical cancer. Full article
(This article belongs to the Special Issue Vaccine Strategies for HPV-Related Cancers)
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15 pages, 1375 KiB  
Article
A Study on the Induction of Multi-Type Immune Responses in Mice via an mRNA Vaccine Based on Hemagglutinin and Neuraminidase Antigen
by Mengyuan Liu, Yixuan Liu, Shaohui Song, Qiurong Qiao, Jing Liu, Yun Xie, Jian Zhou and Guoyang Liao
Vaccines 2025, 13(1), 91; https://doi.org/10.3390/vaccines13010091 - 19 Jan 2025
Viewed by 624
Abstract
Background: The Influenza A virus (IAV), a pathogen affecting the respiratory system, represents a major risk to public health worldwide. Immunization remains the foremost strategy to control the transmission of IAV. The virus has two primary antigens: hemagglutinin (HA) and neuraminidase (NA). Our [...] Read more.
Background: The Influenza A virus (IAV), a pathogen affecting the respiratory system, represents a major risk to public health worldwide. Immunization remains the foremost strategy to control the transmission of IAV. The virus has two primary antigens: hemagglutinin (HA) and neuraminidase (NA). Our previous studies have demonstrated that an IAV NA mRNA vaccine can induce Th1-type immune responses in mice. This research examined the immune responses elicited by an mRNA vaccine targeting both HA and NA antigens in murine models. Methods: In this study, we used two dual-antigen immunization strategies: single-site immunization with an IAV HA+NA mRNA vaccine and multi-site immunization with an IAV HA mRNA vaccine and IAV NA mRNA vaccine. Hemagglutination-inhibiting antibody titer and neutralizing antibody titer in the sera of immunized mice were evaluated, and a viral challenge experiment was conducted. Additionally, the immune responses elicited by the two immunization strategies were characterized using flow cytometry and ELISA. Comparative analyses were performed with mice immunized individually with the IAV HA mRNA vaccine, IAV NA mRNA vaccine, and inactivated vaccine. Results: The results showed that by using a multi-site immunization strategy, mice were able to generate higher levels of hemagglutination-inhibiting and neutralizing antibodies, and were protected in a viral challenge experiment. Moreover, the multi-site regimen also promoted the generation of cytotoxic T cells and maintained a balanced Th1/Th2 immune response. Conclusions: Using mRNA vaccine based on a HA and NA antigen with multi-site immunization strategy can induce higher levels of hemagglutination-inhibiting and neutralizing antibodies, and multi-type immune responses in mice, providing new theoretical and experimental support for advancing upcoming influenza vaccines. Full article
(This article belongs to the Special Issue Innovations in Vaccine Technology)
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18 pages, 1949 KiB  
Article
Antibody Responses to mRNA COVID-19 Vaccine Among Healthcare Workers in Outpatient Clinics in Japan
by Teruhime Otoguro, Keita Wagatsuma, Toshiharu Hino, The Society of Ambulatory and General Pediatrics of Japan, Yusuke Ichikawa, Tri Bayu Purnama, Yuyang Sun, Jiaming Li, Irina Chon, Hisami Watanabe and Reiko Saito
Vaccines 2025, 13(1), 90; https://doi.org/10.3390/vaccines13010090 - 18 Jan 2025
Viewed by 758
Abstract
Background: This study aimed to assess the antibody response to SARS-CoV-2 vaccines among healthcare workers (HCWs) from multiple outpatient clinics in Japan, examining the effects of baseline characteristics (e.g., sex, age, underlying condition, smoking history, occupation) and prior infections. Methods: A total of [...] Read more.
Background: This study aimed to assess the antibody response to SARS-CoV-2 vaccines among healthcare workers (HCWs) from multiple outpatient clinics in Japan, examining the effects of baseline characteristics (e.g., sex, age, underlying condition, smoking history, occupation) and prior infections. Methods: A total of 101 HCWs provided serum at four time points between October 2020 and July 2023. HCWs received two to six doses of mRNA vaccine (BNT162b2 or mRNA-1273). Anti-nucleocapsid (N) and anti-spike (S) IgG antibodies against the ancestral Wuhan strain were measured using the Abbott Architect™ SARS-CoV-2 IgG assay. Univariate and regression analysis evaluated factors such as past infections, age, sex, smoking, underlying condition, and occupation. Results: After four to six doses, the median anti-S IgG titer in uninfected HCWs was 1807.30 BAU/mL, compared to 1899.89 BAU/mL in HCWs with prior infections. The median anti-N IgG titer was 0.10 index S/C in uninfected HCWs and 0.39 index S/C in infected HCWs. HCWs with prior infection had anti-S IgG titers 1.1 to 5.8 times higher than those without. Univariate and multivariate analyses indicated infection and vaccination significantly increased anti-S and anti-N IgG titers. Age, sex, smoking history and occupation did not influence antibody titers while underlying conditions were associated with lower anti-N IgG titers. Conclusions: Infection and vaccination were strongly associated with an increase in anti-S and anti-N IgG titers; however, the impact of hybrid immunity appeared to be limited and varied depending on the timing of the sampling. These findings provide valuable insights for developing personalized vaccination strategies and future vaccine development. Full article
(This article belongs to the Special Issue Detection of SARS-CoV-2 Neutralizing Antibodies and Vaccine Development: 2nd Edition)
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27 pages, 5039 KiB  
Article
Protective Efficacy of Decreasing Antigen Doses of a Chlamydia abortus Subcellular Vaccine Against Ovine Enzootic Abortion in a Pregnant Sheep Challenge Model
by Morag Livingstone, Kevin Aitchison, Javier Palarea-Albaladejo, Francesco Ciampi, Clare Underwood, Antonia Paladino, Francesca Chianini, Gary Entrican, Sean Ranjan Wattegedera and David Longbottom
Vaccines 2025, 13(1), 89; https://doi.org/10.3390/vaccines13010089 - 18 Jan 2025
Viewed by 560
Abstract
Background/Objective: Chlamydia abortus, the cause of ovine enzootic abortion, is a zoonotic bacterial pathogen and one of the most infectious causes of foetal death in sheep worldwide. Although the disease can be controlled using commercial inactivated and live whole-organism vaccines, there are [...] Read more.
Background/Objective: Chlamydia abortus, the cause of ovine enzootic abortion, is a zoonotic bacterial pathogen and one of the most infectious causes of foetal death in sheep worldwide. Although the disease can be controlled using commercial inactivated and live whole-organism vaccines, there are issues with both, particularly concerning efficacy and safety. Recently, we have described the development of a new COMC (chlamydial outer membrane complex) vaccine based on a detergent-extracted outer membrane protein preparation of the pathogen, which can be delivered in a single inoculation and is both efficacious and safe. Methods: In this study, we have evaluated the COMC vaccine further in a dose–response titration of the chlamydial antigen content of the vaccine (from 20 to 2.5 µg in seven experimental groups) using an established pregnant sheep challenge model. Results: No obvious dose–response relationship was observed across the groups, with a single abortion event occurring in four of the groups and three in the lowest dose group (2.5 µg). No abortions occurred in the 15 and 10 µg groups. The abortion rates (0–14%) were significantly below that of the challenge control group (33%). A similar reduction in bacterial shedding of infectious organisms following parturition was observed in the vaccinated groups compared to the challenge control group, which is important in terms of reducing potential transmission to naive animals. Conclusions: The results show that a dose of 10 µg antigen in the vaccine will be optimal in terms of maximising efficacy, reducing shedding at parturition, and ensuring it is cost-effective to produce for commercial manufacture. Full article
(This article belongs to the Special Issue Advances in Vaccines against Infectious Diseases)
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14 pages, 2679 KiB  
Article
Negative Association of Gulf War Illness Symptomatology with Predicted Binding Affinity of Anthrax Vaccine Antigen to Human Leukocyte (HLA) Class II Molecules
by Lisa M. James and Apostolos P. Georgopoulos
Vaccines 2025, 13(1), 88; https://doi.org/10.3390/vaccines13010088 - 18 Jan 2025
Viewed by 614
Abstract
Background: Anthrax is a serious disease caused by Bacillus anthracis (B. anthracis) with a very high mortality when the spores of B. anthracis are inhaled (inhalational anthrax). Aerosolized B. anthracis spores can be used as a deadly bioweapon. Vaccination against anthrax [...] Read more.
Background: Anthrax is a serious disease caused by Bacillus anthracis (B. anthracis) with a very high mortality when the spores of B. anthracis are inhaled (inhalational anthrax). Aerosolized B. anthracis spores can be used as a deadly bioweapon. Vaccination against anthrax is the only effective preventive measure and, hence, the anthrax vaccine was administered to United States (and other) troops during the 1990–91 Gulf War. However, the anthrax vaccine is not harmless, and the anthrax vaccination has been linked to the occurrence and severity of Gulf War Illness (GWI), a debilitating Chronic Multisymptom Illness (CMI). We hypothesized that this is partly due to the combination of two factors, namely (a) the cytotoxicity of the antigen (anthrax Protective Antigen, PA) contained in the vaccine, and (b) the Human Leukocyte Antigen (HLA) genotype of susceptible vaccinees, reducing their ability to make antibodies against the cytotoxic PA. Method: Here, we tested this hypothesis by determining the association between severity of GWI symptoms in 458 GW veterans and the overall strength of the binding affinity of the PA epitopes to the specific six Human Leukocyte Antigen (HLA) Class II alleles carried by each individual (two of each of the HLA-II genes: DPB1, DQB1, DRB1), responsible for initiating the process of antibody production in otherwise immunocompetent individuals, estimated in silico. Results: We found that the severity of GWI symptomatology was negatively and significantly correlated with the strength of the predicted binding affinity of PA peptides to HLA-II molecules (r=−0.356, p<0.001); the stronger the overall binding affinity, the weaker the symptoms. Since the binding of a peptide to an HLA-II molecule is the first and necessary step in initiating the production of antibodies, the findings above support our hypothesis that the severity of GWI symptomatology is partly due to a lack of HLA-II protection. Conclusions: Reduced HLA protection against the toxic anthrax vaccine may underlie GWI. Full article
(This article belongs to the Special Issue Human Leukocyte Antigen (HLA)—Antigen Interactions in Vaccine Development)
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10 pages, 417 KiB  
Conference Report
NIAID Workshop Report: Systematic Approaches for ESKAPE Bacteria Antigen Discovery
by Inka Sastalla, Keehwan Kwon, Clayton Huntley, Kimberly Taylor, Liliana Brown, Tamika Samuel and Lanling Zou
Vaccines 2025, 13(1), 87; https://doi.org/10.3390/vaccines13010087 - 18 Jan 2025
Viewed by 413
Abstract
On 14–15 November 2023, the National Institute of Allergy and Infectious Diseases (NIAID) organized a workshop entitled “Systematic Approaches for ESKAPE Bacteria Antigen Discovery”. The goal of the workshop was to engage scientists from diverse relevant backgrounds to explore novel technologies that can [...] Read more.
On 14–15 November 2023, the National Institute of Allergy and Infectious Diseases (NIAID) organized a workshop entitled “Systematic Approaches for ESKAPE Bacteria Antigen Discovery”. The goal of the workshop was to engage scientists from diverse relevant backgrounds to explore novel technologies that can be harnessed to identify and address current roadblocks impeding advances in antigen and vaccine discoveries for the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species). The workshop consisted of four sessions that addressed ESKAPE infections, antigen discovery and vaccine efforts, and new technologies including systems immunology and vaccinology approaches. Each session was followed by a panel discussion. In total, there were over 260 in-person and virtual attendees, with high levels of engagement. This report provides a summary of the event and highlights challenges and opportunities in the field of ESKAPE vaccine discovery. Full article
(This article belongs to the Special Issue Impact of Vaccines and Vaccination on the Gut Microbiota)
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27 pages, 4069 KiB  
Article
The Long-Term Immunity of a Microneedle Array Patch of a SARS-CoV-2 S1 Protein Subunit Vaccine Irradiated by Gamma Rays in Mice
by Eun Kim, Muhammad S. Khan, Juyeop Shin, Shaohua Huang, Alessandro Ferrari, Donghoon Han, Eunjin An, Thomas W. Kenniston, Irene Cassaniti, Fausto Baldanti, Dohyeon Jeong and Andrea Gambotto
Vaccines 2025, 13(1), 86; https://doi.org/10.3390/vaccines13010086 - 18 Jan 2025
Viewed by 601
Abstract
Background/Objectives: COVID-19 vaccines effectively prevent severe disease, but unequal distribution, especially in low- and middle-income countries, has led to vaccine-resistant strains. This highlights the urgent need for alternative vaccine platforms that are safe, thermostable, and easy to distribute. This study evaluates the immunogenicity, [...] Read more.
Background/Objectives: COVID-19 vaccines effectively prevent severe disease, but unequal distribution, especially in low- and middle-income countries, has led to vaccine-resistant strains. This highlights the urgent need for alternative vaccine platforms that are safe, thermostable, and easy to distribute. This study evaluates the immunogenicity, stability, and scalability of a dissolved microneedle array patch (MAP) delivering the rS1RS09 subunit vaccine, comprising the SARS-CoV-2 S1 monomer and RS09, a TLR-4 agonist peptide. Methods: The rS1RS09 vaccine was administered via MAP or intramuscular injection in murine models. The immune responses of the MAP with and without gamma irradiation as terminal sterilization were assessed at doses of 5, 15, and 45 µg, alongside neutralizing antibody responses to Wuhan, Delta, and Omicron variants. The long-term storage stability was also evaluated through protein degradation analyses at varying temperatures. Results: The rS1RS09 vaccine elicited stronger immune responses and ACE2-binding inhibition than S1 monomer alone or trimer. The MAP delivery induced sgnificantly higher and longer-lasting S1-specific IgG responses for up to 70 weeks compared to intramuscular injections. Robust Th2-prevalent immune responses were generated in all the groups vaccinated via the MAP and significant neutralizing antibodies were elicited at 15 and 45 µg, showing dose-sparing potential. The rS1RS09 in MAP has remained stable with minimal protein degradation for 19 months at room temperature or under refrigeration, regardless of gamma-irradiation. After an additional month of storage at 42 °C, cit showed less than 3% degradation, ompared to over 23% in liquid vaccines Conclusions: Gamma-irradiated MAP-rS1RS09 is a promising platform for stable, scalable vaccine production and distribution, eliminating cold chain logistics. These findings support its potential for mass vaccination efforts, particularly in resource-limited settings. Full article
(This article belongs to the Special Issue Research on Immune Response and Vaccines: 2nd Edition)
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17 pages, 1774 KiB  
Systematic Review
Safety, Immunogenicity, and Efficacy of Cytomegalovirus Vaccines: A Systematic Review of Randomized Controlled Trials
by Manuela Chiavarini, Anita Genga, Giorgia Maria Ricciotti, Marcello Mario D’Errico and Pamela Barbadoro
Vaccines 2025, 13(1), 85; https://doi.org/10.3390/vaccines13010085 - 17 Jan 2025
Viewed by 640
Abstract
Background/Objectives: Cytomegalovirus (CMV) is widespread and mostly causes asymptomatic infections in immunocompetent hosts, but it may lead to severe and life-threatening diseases in immunocompromised individuals, such as transplant patients and congenitally infected children, representing a significant public health concern. Although there are no [...] Read more.
Background/Objectives: Cytomegalovirus (CMV) is widespread and mostly causes asymptomatic infections in immunocompetent hosts, but it may lead to severe and life-threatening diseases in immunocompromised individuals, such as transplant patients and congenitally infected children, representing a significant public health concern. Although there are no licensed CMV vaccines, the development of a CMV vaccine is considered a high priority due to its potential to reduce the burden associated with CMV-related complications, and several approaches are under investigation. The objective of this systematic review was to synthesize the evidence on various CMV vaccines currently under clinical development. Methods: According to the PRISMA guidelines (PROSPERO ID: CRD42024516601), a comprehensive literature search was conducted to identify all the randomized controlled trials that have evaluated the safety, immunogenicity, and efficacy of vaccine candidates compared to a placebo. A total of 26 studies were identified: 11 on transplant patients and 15 on healthy individuals. Results: Several vaccine candidates have shown encouraging results in terms of safety and specific immune responses, notably adjuvanted gB vaccines and DNA vaccines targeting gB and pp65. The results were divided into RCTs on healthy individuals and those on transplant recipients, because the CMV-specific immune response to a vaccine is complex and varies depending not only on the type of vaccine, but also on the immunological status of the individual. Conclusions: Challenges remain in achieving broad efficacy across diverse populations, particularly for immunocompromised patients. Thus, the present work seeks to support future decisions and guide further research in the development of an effective and widely available CMV vaccine. Full article
(This article belongs to the Special Issue State-of-the-Art Vaccine Researches)
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15 pages, 3580 KiB  
Article
Immunogenicity of HIV-1 Env mRNA and Env-Gag VLP mRNA Vaccines in Mice
by Qi Ma, Jing Yang, Xiaoguang Zhang, Hongxia Li, Yanzhe Hao and Xia Feng
Vaccines 2025, 13(1), 84; https://doi.org/10.3390/vaccines13010084 - 17 Jan 2025
Viewed by 680
Abstract
Background: The development of a protective vaccine is critical for conclusively ending the human immunodeficiency virus (HIV) epidemic. Methods: We constructed nucleotide-modified mRNA vaccines expressing HIV-1 Env and Gag proteins. Env–gag virus-like particles (VLPs) were generated through co-transfection with env and gag mRNA [...] Read more.
Background: The development of a protective vaccine is critical for conclusively ending the human immunodeficiency virus (HIV) epidemic. Methods: We constructed nucleotide-modified mRNA vaccines expressing HIV-1 Env and Gag proteins. Env–gag virus-like particles (VLPs) were generated through co-transfection with env and gag mRNA vaccines. BALB/c mice were immunized with env mRNA, env–gag VLP mRNA, env plasmid DNA vaccine, or lipid nanoparticle (LNP) controls. HIV Env-specific binding and neutralizing antibodies in mouse sera were assessed via enzyme-linked immunosorbent assay (ELISA) and pseudovirus-based neutralization assays, respectively. Env-specific cellular immune responses in mouse splenocytes were evaluated using an Enzyme-linked immunosorbent assay (ELISpot) and in vivo cytotoxic T cell-killing assays. Results: The Env-specific humoral and cellular immune responses elicited by HIV-1 env mRNA and env–gag VLP mRNA vaccine were stronger than those induced by the DNA vaccine. Specific immune responses induced by the env mRNA vaccine were significantly stronger in the high-dose group than in the low-dose group. Immunization with co-formulated env and gag mRNAs elicited superior cellular immune responses compared to env mRNA alone. Conclusions: These findings suggest that the env–gag VLP mRNA platform holds significant promise for HIV-1 vaccine development. Full article
(This article belongs to the Special Issue Research on HIV/AIDS Vaccine)
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16 pages, 232 KiB  
Article
Provider Preference, Logistical Challenges, or Vaccine Hesitancy? Analyzing Parental Decision-Making in School Vaccination Programs: A Qualitative Study in Sydney, Australia
by Leigh McIndoe, Alexandra Young, Cristyn Davies, Cassandra Vujovich-Dunn, Stephanie Kean, Michelle Dives and Vicky Sheppeard
Vaccines 2025, 13(1), 83; https://doi.org/10.3390/vaccines13010083 - 17 Jan 2025
Viewed by 490
Abstract
Background: School-based immunization programs are crucial for equitable vaccine coverage, yet their success depends on parental consent processes. This study investigates patterns of vaccine decision-making within Australia’s school-based immunization program, specifically focusing on human papillomavirus (HPV) and diphtheria-tetanus-pertussis (dTpa) vaccines offered free to [...] Read more.
Background: School-based immunization programs are crucial for equitable vaccine coverage, yet their success depends on parental consent processes. This study investigates patterns of vaccine decision-making within Australia’s school-based immunization program, specifically focusing on human papillomavirus (HPV) and diphtheria-tetanus-pertussis (dTpa) vaccines offered free to adolescents aged 12–13. Methods: This qualitative study was conducted in the South Eastern Sydney Local Health District (2022–2023). Semi-structured interviews were held with school staff (n = 11) across government, Catholic, and independent schools, parents whose children were not vaccinated at school (n = 11) and a focus group with public health unit staff (n = 5). Data were analyzed to identify key barriers and patterns in vaccine decision-making. Results: Analysis revealed three distinct groups of parents whose children were not vaccinated through the school program: (1) those favoring general practitioners for vaccination, driven by trust in medical providers and a preference for personalized care; (2) those intending to consent but facing logistical barriers, including communication breakdowns and online consent challenges; and (3) vaccine-hesitant parents, particularly regarding HPV vaccination, influenced by safety concerns and misinformation. These findings demonstrate that non-participation in school vaccination programs should not be automatically equated with vaccine hesitancy. Conclusions: Tailored interventions are necessary for addressing vaccine non-participation. Recommendations include strengthening collaboration with general practitioners, streamlining consent processes and providing targeted education to counter misinformation. This study provides valuable insights into social determinants of vaccine acceptance and offers actionable strategies for improving vaccine uptake in school-based programs. Full article
(This article belongs to the Special Issue Advancing the Science on Vaccine Hesitancy to Inform Interventions)
14 pages, 1446 KiB  
Article
Persistence of the Immune Response to an Intramuscular Bivalent (GI.1/GII.4) Norovirus Vaccine in Adults
by Geert Leroux-Roels, Robert L. Atmar, Jakob P. Cramer, Ian Escudero and Astrid Borkowski
Vaccines 2025, 13(1), 82; https://doi.org/10.3390/vaccines13010082 - 17 Jan 2025
Viewed by 586
Abstract
Background: Major global economic and health burdens due to norovirus gastroenteritis could be addressed by an effective vaccine. Methods: In this study, 428 adult recipients of various compositions of the norovirus vaccine candidate, HIL-214, were followed for 5 years, to assess immune responses [...] Read more.
Background: Major global economic and health burdens due to norovirus gastroenteritis could be addressed by an effective vaccine. Methods: In this study, 428 adult recipients of various compositions of the norovirus vaccine candidate, HIL-214, were followed for 5 years, to assess immune responses to its virus-like particle antigens, GI.1 and GII.4c. Serum antibodies and peripheral-blood antibody-secreting cells (ASCs) were measured. This report focuses on the single-dose 15/50 (µg GI.1/GII.4c) composition, which had been selected for further clinical development. Results: For single-dose 15/50 recipients (N = 105), GI.1-specific and GII.4c-specific histoblood-group antigen-blocking (HBGA) antibodies appeared to have persisted to 5 years, waning from a peak at 4 to 8 weeks, and plateauing above baseline after 3 years. From 3 to 5 years, GI.1-specific GMTs ranged between 53 (95%CI, 40–71) and 60 (95%CI, 46–77; N = 69–97) and were approximately 2-fold above the baseline GMT (24 (95%CI, 20–28); N = 105). GII.4c-specific GMTs ranged between 103 (95%CI, 77–138) and 114 (95%CI, 86–152; N = 70–97) and were above baseline, but by less than 2-fold (70 (95%CI, 53–92); N = 105). Similar kinetics were observed for pan-Ig titers and ASCs in a subset. Similar kinetics were also observed for HBGA and pan-Ig titers in recipients of other 15/50 dosages. Conclusions: Immune responses to HIL-214 in adults appear to persist for five years. Full article
(This article belongs to the Section Vaccines against Infectious Diseases)
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18 pages, 4567 KiB  
Article
The Development of a Novel Broad-Spectrum Influenza Polypeptide Vaccine Based on Multi-Epitope Tandem Sequences
by Song Zhao, Junhao Luo, Wenhui Guo, Li Li, Siyu Pu, Libo Dong, Wenfei Zhu and Rongbao Gao
Vaccines 2025, 13(1), 81; https://doi.org/10.3390/vaccines13010081 - 17 Jan 2025
Viewed by 739
Abstract
Background: Polypeptide vaccines have the potential to improve immune responses by targeting conserved and weakly immunogenic regions in antigens. This study aimed to identify and evaluate the efficacy of a novel influenza universal vaccine candidate consisting of multiple polypeptides derived from highly conserved [...] Read more.
Background: Polypeptide vaccines have the potential to improve immune responses by targeting conserved and weakly immunogenic regions in antigens. This study aimed to identify and evaluate the efficacy of a novel influenza universal vaccine candidate consisting of multiple polypeptides derived from highly conserved regions of influenza virus proteins hemagglutinin (HA), neuraminidase (NA), and matrix protein 2 (M2). Methods: Immunoinformatics tools were used to screen conserved epitopes from different influenza virus subtypes (H1N1, H3N2, H5N1, H7N9, H9N2, and IBV). A polypeptide vaccine, P125-H, was constructed by linking multiple epitopes using Ii-Key technology. The immunogenicity of P125-H was assessed in mice using MF59-adjuvanted P125-H via intraperitoneal injection. Hemagglutination inhibition (HI) and neutralizing antibody responses were measured, along with IFN-γ levels in spleen lymphocytes. Protective efficacy was evaluated using viral challenge with lethal doses of H1N1 and H7N9. Results: Mice immunized with P125-H generated high levels of HI and neutralizing antibodies against multiple influenza strains. IFN-γ production was significantly elevated in spleen lymphocytes upon stimulation with the vaccine. P125-H protected mice from influenza infection, reducing weight loss and the viral load in the lungs, mitigating lung pathology, and decreasing mortality. Conclusions: The P125-H vaccine induced broad cross-protection against multiple influenza strains and elicited robust immune responses. It demonstrates strong potential as a candidate for a universal influenza vaccine. Full article
(This article belongs to the Section Influenza Virus Vaccines)
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11 pages, 1369 KiB  
Article
Strengthening National Immunization Technical Advisory Groups: Twelve Years of Progress (2012–2023)
by Louise Henaff, Laure Dumolard, Vinod Bura, Gerald Etapelong Sume, Sidy Ndiaye, Jennifer Sanwogou, Heeyoun Cho, Joachim Hombach and Christoph A. Steffen
Vaccines 2025, 13(1), 80; https://doi.org/10.3390/vaccines13010080 - 17 Jan 2025
Viewed by 848
Abstract
Introduction: Well-functioning National Immunization Technical Advisory Groups (NITAGs) are valuable contributors to decision-making processes in the complex immunization policy arena. This paper describes the progress made globally on the establishment and strengthening of these key advisory groups and discusses some of their strengths, [...] Read more.
Introduction: Well-functioning National Immunization Technical Advisory Groups (NITAGs) are valuable contributors to decision-making processes in the complex immunization policy arena. This paper describes the progress made globally on the establishment and strengthening of these key advisory groups and discusses some of their strengths, challenges, and opportunities. Methods: The data submitted annually by countries to the World Health Organization (WHO) via the WHO/UNICEF Joint Reporting Form (JRF) were analyzed, comparing the NITAG functionality criteria in 2012 and 2023. Results: In 2023 and 2012, 88% and 61% of countries, respectively, reported having a NITAG. A total of 77% of NITAGs met all six NITAG process criteria in 2023 compared to 33% in 2012. This progress was most notable in the WHO African Region, increasing from 7% (2012) to 77% (2023), and the South-East Asia Region, increasing from 45% (2012) to 91% (2023). In 2023, 84% of NITAGs issued a vaccine-policy recommendation that was adopted by decision-makers. Discussion: Marked progress has been made since 2012 on establishing and maintaining NITAGs, with a small number of countries yet to form an advisory committee. Supporting and sustaining NITAG functions remains an important means for countries to foster independent and transparent expert advice on vaccine and immunization policy. Setbacks in countries facing instability or political turmoil are a reminder of the reversibility of progress. WHO and partners play an important role in supporting countries in strengthening these advisory committees. Continuous commitment by countries to the function and involvement of NITAGs in policy recommendations is essential for enhancing the strength and resilience of immunization programs. Full article
(This article belongs to the Special Issue 50 Years of Immunization—Steps Forward)
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12 pages, 9100 KiB  
Article
Inactivation of Zika Virus with Hydroxypropyl-Beta-Cyclodextrin
by Cory R. Hewitt, Nicholas J. Wixon, Arthur Gallegos, You Zhou, Victor C. Huber and M. Scott Killian
Vaccines 2025, 13(1), 79; https://doi.org/10.3390/vaccines13010079 - 16 Jan 2025
Viewed by 603
Abstract
Background/Objectives: Zika virus (ZIKV) infection is associated with life-threatening diseases in humans. To date, there are no available FDA-approved therapies or vaccines for the specific treatment or prevention of ZIKV infection. Variation in the ZIKV envelope protein (Env), along with its complex [...] Read more.
Background/Objectives: Zika virus (ZIKV) infection is associated with life-threatening diseases in humans. To date, there are no available FDA-approved therapies or vaccines for the specific treatment or prevention of ZIKV infection. Variation in the ZIKV envelope protein (Env), along with its complex quaternary structure, presents challenges to synthetic approaches for developing an effective vaccine and broadly neutralizing antibodies (bnAbs). We hypothesized that beta-cyclodextrin (BCD) could be used to uniquely inactivate infectious ZIKV without disruption of Env. Methods: ZIKV was propagated in Vero cells and admixed with BCD. The BCD-treated ZIKV was evaluated for infectivity using immunofluorescence and quantitative RT-PCR (qRT-PCR) assays, for immunoreactivity in Western blots, structural integrity by electron microscopy, and immunogenicity in mice. Results: Here, we show that 200 mM BCD-treated ZIKV is non-infectious in cell culture, remains immunoreactive with an Env-specific antibody, retains its virion shape and size, and elicits the production of immunogen-specific antibodies in immunized mice. Conclusions: These results indicate that BCD can be used to safely inactivate ZIKV, and they provide insights for vaccine and antibody development. Full article
(This article belongs to the Special Issue Vaccines against Flaviviruses and Alphaviruses: Recent Advances and Future Challenges)
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7 pages, 186 KiB  
Commentary
Elegant and Innovative Recoding Strategies for Advancing Vaccine Development
by François Meurens, Fanny Renois and Uladzimir Karniychuk
Vaccines 2025, 13(1), 78; https://doi.org/10.3390/vaccines13010078 - 16 Jan 2025
Viewed by 497
Abstract
Recoding strategies have emerged as a promising approach for developing safer and more effective vaccines by altering the genetic structure of microorganisms, such as viruses, without changing their proteins. This method enhances vaccine safety and efficacy while minimizing the risk of reversion to [...] Read more.
Recoding strategies have emerged as a promising approach for developing safer and more effective vaccines by altering the genetic structure of microorganisms, such as viruses, without changing their proteins. This method enhances vaccine safety and efficacy while minimizing the risk of reversion to virulence. Recoding enhances the frequency of CpG dinucleotides, which in turn activates immune responses and ensures a strong attenuation of the pathogens. Recent advancements highlight synonymous recoding’s potential, offering improved genetic stability and immunogenicity compared to traditional methods. Live vaccines attenuated using classical methods pose a risk of reversion to virulence and can be time-consuming to produce. Synonymous recoding, involving numerous codon alterations, boosts safety and vaccine stability. One challenge is balancing attenuation with yield; however, innovations like Zinc-finger antiviral protein (ZAP) knockout cell lines can enhance vaccine production. Beyond viral vaccines, recoding can apply to bacterial vaccines, as exemplified by modified Escherichia coli and Streptococcus pneumoniae strains, which show reduced virulence. Despite promising results, challenges like ensuring genetic stability, high yield, and regulatory approval remain. Briefly, ongoing research aims to harness these innovations for comprehensive improvements in vaccine design and deployment. In this commentary, we sought to further engage the community’s interest in this elegant approach by briefly highlighting its main advantages, disadvantages, and future prospects. Full article
(This article belongs to the Section Attenuated/Inactivated/Live and Vectored Vaccines)
15 pages, 1520 KiB  
Article
Economic and Clinical Benefits of Bivalent Respiratory Syncytial Virus Prefusion F (RSVpreF) Maternal Vaccine for Prevention of RSV in Infants: A Cost-Effectiveness Analysis for Mexico
by José Luis Huerta, Robyn Kendall, Luka Ivkovic, Carlos Molina, Amy W. Law and Diana Mendes
Vaccines 2025, 13(1), 77; https://doi.org/10.3390/vaccines13010077 - 16 Jan 2025
Viewed by 821
Abstract
Background/Objectives: Respiratory syncytial virus (RSV) is a leading cause of respiratory infections in children. A novel RSVpreF vaccine for use among pregnant women for the prevention of RSV in infants is expected to be licensed in Mexico. Hence, the clinical and economic burden [...] Read more.
Background/Objectives: Respiratory syncytial virus (RSV) is a leading cause of respiratory infections in children. A novel RSVpreF vaccine for use among pregnant women for the prevention of RSV in infants is expected to be licensed in Mexico. Hence, the clinical and economic burden of RSV among infants in Mexico, with and without a year-round RSVpreF maternal vaccination program, was estimated. Methods: A cohort model was developed to project clinical and economic outcomes of RSV from birth to 1 year of age for maternal vaccination and no intervention. Incremental cost-effectiveness ratios were calculated from direct cost outcomes, life years, and quality-adjusted life years (QALYs). The value per dose of the RSVpreF for which the program would be cost-effective was explored. Analyses were conducted from the healthcare system perspective, with direct costs (2024 Mexican Pesos [MXN]) and outcomes discounted at 5% annually; scenario and sensitivity analyses tested the robustness of model settings and inputs. Results: Compared to no intervention, a year-round RSVpreF vaccine administered to 1891 M pregnant women would prevent 15,768 hospitalizations, 5505 emergency department cases, and 5505 physician office visits annually, averting MXN 1754 M in direct medical costs with an increase of 3402 life years or 3666 QALYs. The RSVpreF vaccine would be cost-saving up to MXN 1301/dose and cost-effective up to MXN 2105–MXN 3715/dose under an assumed cost-effectiveness threshold range of 1–3× the gross domestic product (GDP) per capita (MXN 247,310) per QALY gained. Conclusions: Year-round RSVpreF maternal vaccination would substantially reduce RSV’s clinical and economic burden among infants in Mexico and likely be a cost-effective program. Full article
(This article belongs to the Special Issue Impact of Immunization Safety Monitoring on Vaccine Coverage)
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18 pages, 1654 KiB  
Article
The Role of Dendritic Cells in Adaptive Immune Response Induced by OVA/PDDA Nanoparticles
by Daniele R. Pereira, Yunys Pérez-Betancourt, Bianca C. L. F. Távora, Geraldo S. Magalhães, Ana Maria Carmona-Ribeiro and Eliana L. Faquim-Mauro
Vaccines 2025, 13(1), 76; https://doi.org/10.3390/vaccines13010076 - 16 Jan 2025
Viewed by 472
Abstract
Background/Objective: Cationic polymers were shown to assemble with negatively charged proteins yielding nanoparticles (NPs). Poly-diallyl-dimethyl-ammonium chloride (PDDA) combined with ovalbumin (OVA) yielded a stable colloidal dispersion (OVA/PDDA-NPs) eliciting significant anti-OVA immune response. Dendritic cells (DCs), as sentinels of foreign antigens, exert a [...] Read more.
Background/Objective: Cationic polymers were shown to assemble with negatively charged proteins yielding nanoparticles (NPs). Poly-diallyl-dimethyl-ammonium chloride (PDDA) combined with ovalbumin (OVA) yielded a stable colloidal dispersion (OVA/PDDA-NPs) eliciting significant anti-OVA immune response. Dendritic cells (DCs), as sentinels of foreign antigens, exert a crucial role in the antigen-specific immune response. Here, we aimed to evaluate the involvement of DCs in the immune response induced by OVA/PDDA. Methods: In vivo experiments were used to assess the ability of OVA/PDDA-NPs to induce anti-OVA antibodies by ELISA, as well as plasma cells and memory B cells using flow cytometry. Additionally, DC migration to draining lymph nodes following OVA/PDDA-NP immunization was evaluated by flow cytometry. In vitro experiments using bone marrow-derived DCs (BM-DCs) were used to analyze the binding and uptake of OVA/PDDA-NPs, DC maturation status, and their antigen-presenting capacity. Results: Our data confirmed the potent effect of OVA/PDDA-NPs inducing anti-OVA IgG1 and IgG2a antibodies with increased CD19+CD138+ plasma cells and CD19+CD38+CD27+ memory cells in immunized mice. OVA/PDDA-NPs induced DC maturation and migration to draining lymph nodes. The in vitro results showed higher binding and the uptake of OVA/PDDA-NPs by BM-DCs. In addition, the NPs were able to induce the upregulation of costimulatory and MHC-II molecules on DCs, as well as TNF-α and IL-12 production. Higher OVA-specific T cell proliferation was promoted by BM-DCs incubated with OVA/PDDA-NPs. Conclusions: The data showed the central role of DCs in the induction of antigen-specific immune response by OVA-PDDA-NPs, thus proving that these NPs are a potent adjuvant for subunit vaccine design. Full article
(This article belongs to the Special Issue Vaccines Targeting Dendritic Cells)
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13 pages, 1890 KiB  
Article
Development of RT-PCR Assays for Simple Detection and Identification of Sabin Virus Contaminants in the Novel Oral Poliovirus Vaccines
by Olga Singh, Hasmik Manukyan, Erman Tritama, Shwu-Maan Lee, Jerry P. Weir and Majid Laassri
Vaccines 2025, 13(1), 75; https://doi.org/10.3390/vaccines13010075 - 15 Jan 2025
Viewed by 688
Abstract
Background/Objectives: Conventional live oral poliovirus vaccines (OPVs) effectively prevent poliomyelitis. These vaccines are derived from three attenuated Sabin strains of poliovirus, which can revert within the first week of replication to a neurovirulent phenotype, leading to sporadic cases of vaccine-associated paralytic poliomyelitis (VAPP) [...] Read more.
Background/Objectives: Conventional live oral poliovirus vaccines (OPVs) effectively prevent poliomyelitis. These vaccines are derived from three attenuated Sabin strains of poliovirus, which can revert within the first week of replication to a neurovirulent phenotype, leading to sporadic cases of vaccine-associated paralytic poliomyelitis (VAPP) among vaccinees and their contacts. A novel OPV2 vaccine (nOPV2) with enhanced genetic stability was developed recently; type 1 and type 3 nOPV strains were engineered using the nOPV2 genome as a backbone by replacing the capsid precursor polyprotein (P1) with that of Sabin strains type 1 and type 3, respectively. The nOPV vaccines have a high degree of sequence homology with the parental Sabin 2 genome, and some manufacturing facilities produce and store both Sabin OPV and nOPV. Therefore, detecting Sabin virus contaminations in nOPV lots is crucial. Methods: This study describes the development of pan quantitative reverse transcription polymerase chain reaction (panRT-PCR) and multiplex one-step RT-PCR (mosRT-PCR) assays for the straightforward detection and identification of contaminating Sabin viruses when present in significantly higher amounts of nOPV strains. Results: The two assays exhibit high specificity, reproducibility, and sensitivity to detect 0.0001% and 0.00001% of Sabin viruses in nOPV, respectively. Additionally, an analysis of 12 trivalent nOPV formulation lots using both methods confirmed that the nOPV lots were free from Sabin virus contamination. Conclusions: The results demonstrated that the RT-PCR assays are sensitive and specific. These assays are relevant for quality control and lot release of nOPV vaccines. Full article
(This article belongs to the Special Issue Recent Scientific Development of Poliovirus Vaccines)
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22 pages, 7210 KiB  
Article
Single Dose of Attenuated Vaccinia Viruses Expressing H5 Hemagglutinin Affords Rapid and Long-Term Protection Against Lethal Infection with Highly Pathogenic Avian Influenza A H5N1 Virus in Mice and Monkeys
by Fumihiko Yasui, Keisuke Munekata, Tomoko Fujiyuki, Takeshi Kuraishi, Kenzaburo Yamaji, Tomoko Honda, Sumiko Gomi, Misako Yoneda, Takahiro Sanada, Koji Ishii, Yoshihiro Sakoda, Hiroshi Kida, Shosaku Hattori, Chieko Kai and Michinori Kohara
Vaccines 2025, 13(1), 74; https://doi.org/10.3390/vaccines13010074 - 15 Jan 2025
Viewed by 972
Abstract
Background/Objectives: In preparation for a potential pandemic caused by the H5N1 highly pathogenic avian influenza (HPAI) virus, pre-pandemic vaccines against several viral clades have been developed and stocked worldwide. Although these vaccines are well tolerated, their immunogenicity and cross-reactivity with viruses of different [...] Read more.
Background/Objectives: In preparation for a potential pandemic caused by the H5N1 highly pathogenic avian influenza (HPAI) virus, pre-pandemic vaccines against several viral clades have been developed and stocked worldwide. Although these vaccines are well tolerated, their immunogenicity and cross-reactivity with viruses of different clades can be improved. Methods: To address this aspect, we generated recombinant influenza vaccines against H5-subtype viruses using two different strains of highly attenuated vaccinia virus (VACV) vectors. Results: rLC16m8-mcl2.2 hemagglutinin (HA) and rLC16m8-mcl2.3.4 HA consisted of a recombinant LC16m8 vector encoding the HA protein from clade 2.2 or clade 2.3.4 viruses (respectively); rDIs-mcl2.2 HA consisted of a recombinant DIs vector encoding the HA protein from clade 2.2. A single dose of rLC16m8-mcl2.2 HA showed rapid (1 week after vaccination) and long-term protection (20 months post-vaccination) in mice against the HPAI H5N1 virus. Moreover, cynomolgus macaques immunized with rLC16m8-mcl2.2 HA exhibited long-term protection when challenged with a heterologous clade of the HPAI H5N1 virus. Although the DIs strain is unable to grow in most mammalian cells, rDIs-mcl2.2 HA also showed rapid and long-lasting effects against HPAI H5N1 virus infection. Notably, the protective efficacy of rDIs-mcl2.2 HA was comparable to that of rLC16m8-mcl2.2 HA. Furthermore, these vaccines protected animals previously immunized with VACVs from a lethal challenge with the HPAI H5N1 virus. Conclusions: These results suggest that both rLC16m8-mcl2.2 HA and rDIs-mcl2.2 HA are effective in preventing HPAI H5N1 virus infection, and rDIs-mcl2.2 HA is a promising vaccine candidate against H5 HA-subtype viruses. Full article
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13 pages, 256 KiB  
Review
Strategic and Technical Considerations in Manufacturing Viral Vector Vaccines for the Biomedical Advanced Research and Development Authority Threats
by Lindsay A. Parish, Shyam Rele, Kimberly A. Hofmeyer, Brooke B. Luck and Daniel N. Wolfe
Vaccines 2025, 13(1), 73; https://doi.org/10.3390/vaccines13010073 - 14 Jan 2025
Viewed by 1306
Abstract
Over the past few decades, the world has seen a considerable uptick in the number of new and emerging infectious disease outbreaks. The development of new vaccines, vaccine technologies, and platforms are critical to enhance our preparedness for biological threats and prevent future [...] Read more.
Over the past few decades, the world has seen a considerable uptick in the number of new and emerging infectious disease outbreaks. The development of new vaccines, vaccine technologies, and platforms are critical to enhance our preparedness for biological threats and prevent future pandemics. Viral vectors can be an important tool in the repertoire of technologies available to develop effective vaccines against new and emerging infectious diseases. In many instances, vaccines may be needed in a reactive scenario, requiring technologies than can elicit rapid and robust immune responses with a single dose. Here, we discuss how viral vector vaccines are utilized in a vaccine portfolio for priority biological threats, some of the challenges in manufacturing viral vector vaccines, the need to strengthen live virus manufacturing capabilities, and future opportunities to capitalize on the use of viral vectors to improve the sustainability of the Biomedical Advanced Research and Development Authority’s vaccine portfolio. Full article
(This article belongs to the Special Issue Strategies of Viral Vectors for Vaccine Development)
12 pages, 707 KiB  
Review
Exploitation of Unconventional CD8 T-Cell Responses Induced by Engineered Cytomegaloviruses for the Development of an HIV-1 Vaccine
by Joseph Bruton and Tomáš Hanke
Vaccines 2025, 13(1), 72; https://doi.org/10.3390/vaccines13010072 - 14 Jan 2025
Viewed by 1180
Abstract
After four decades of intensive research, traditional vaccination strategies for HIV-1 remain ineffective due to HIV-1′s extraordinary genetic diversity and complex immune evasion mechanisms. Cytomegaloviruses (CMV) have emerged as a novel type of vaccine vector with unique advantages due to CMV persistence and [...] Read more.
After four decades of intensive research, traditional vaccination strategies for HIV-1 remain ineffective due to HIV-1′s extraordinary genetic diversity and complex immune evasion mechanisms. Cytomegaloviruses (CMV) have emerged as a novel type of vaccine vector with unique advantages due to CMV persistence and immunogenicity. Rhesus macaques vaccinated with molecular clone 68-1 of RhCMV (RhCMV68-1) engineered to express simian immunodeficiency virus (SIV) immunogens elicited an unconventional major histocompatibility complex class Ib allele E (MHC-E)-restricted CD8+ T-cell response, which consistently protected over half of the animals against a highly pathogenic SIV challenge. The RhCMV68-1.SIV-induced responses mediated a post-infection replication arrest of the challenge virus and eventually cleared it from the body. These observations in rhesus macaques opened a possibility that MHC-E-restricted CD8+ T-cells could achieve similar control of HIV-1 in humans. The potentially game-changing advantage of the human CMV (HCMV)-based vaccines is that they would induce protective CD8+ T-cells persisting at the sites of entry that would be insensitive to HIV-1 evasion. In the RhCMV68-1-protected rhesus macaques, MHC-E molecules and their peptide cargo utilise complex regulatory mechanisms and unique transport patterns, and researchers study these to guide human vaccine development. However, CMVs are highly species-adapted viruses and it is yet to be shown whether the success of RhCMV68-1 can be translated into an HCMV ortholog for humans. Despite some safety concerns regarding using HCMV as a vaccine vector in humans, there is a vision of immune programming of HCMV to induce pathogen-tailored CD8+ T-cells effective against HIV-1 and other life-threatening diseases. Full article
(This article belongs to the Special Issue Advances in Vaccines against Infectious Diseases)
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13 pages, 209 KiB  
Article
Seasonal Influenza Vaccination Uptake Among Australian Healthcare Professionals: An Archetype for Success
by Caroline M. Hall, Anthony Cotton, Adrian Webster, Mary Bushell and Holly L. Northam
Vaccines 2025, 13(1), 71; https://doi.org/10.3390/vaccines13010071 - 14 Jan 2025
Viewed by 589
Abstract
Background/Objectives: Qualitative research suggests there may be identifiable characteristics that form a health professional (HCP) archetype associated with habitual seasonal influenza vaccination (SIV). However, the validity of this archetype requires further investigation, ideally within a theoretical framework that can elucidate this association and [...] Read more.
Background/Objectives: Qualitative research suggests there may be identifiable characteristics that form a health professional (HCP) archetype associated with habitual seasonal influenza vaccination (SIV). However, the validity of this archetype requires further investigation, ideally within a theoretical framework that can elucidate this association and its generalisability to other vaccines. This study aims to confirm key HCP archetype characteristics associated with SIV, as informed by prior qualitative research findings, and test the generalisability of the association between this archetype and SIV to COVID-19 vaccine acceptance. Method: A cross-sectional survey was designed and distributed to an Australian HCP sample consisting of practicing nurses, midwives, pharmacists, and medical practitioners. The anonymous online survey measured key characteristics that predict vaccination behaviour and intention. Results: Most participants (n = 173) demonstrated habitual SIV behaviour (77.91%) associated with the intention to vaccinate in the future. Survey findings supported the HCP archetype, as key constructs were associated with vaccination intention and behaviour, including heightened professional responsibility, vaccine confidence, and protection of self and patients. Furthermore, results suggested progressing vaccination intention to behaviour, overcoming vaccine complacency, is possible through the provision of free, accessible vaccination services. These critical factors were broadly generalisable to the COVID-19 vaccine. Conclusions: A vaccination-positive HCP archetype, supported by access to free, convenient vaccination services, was associated with the likelihood of future vaccination behaviour, including in future pandemic response scenarios. However, it will be important to ensure that HCP vaccine knowledge gaps are minimised to enhance trust in this cohort to enable broad success. Full article
21 pages, 3533 KiB  
Article
T4 Phage Displaying Dual Antigen Clusters Against H3N2 Influenza Virus Infection
by Shenglong Liu, Mengzhou Lin and Xin Zhou
Vaccines 2025, 13(1), 70; https://doi.org/10.3390/vaccines13010070 - 13 Jan 2025
Viewed by 723
Abstract
Background: The current H3N2 influenza subunit vaccine exhibits weak immunogenicity, which limits its effectiveness in preventing and controlling influenza virus infections. Methods: In this study, we aimed to develop a T4 phage-based nanovaccine designed to enhance the immunogenicity of two antigens by displaying [...] Read more.
Background: The current H3N2 influenza subunit vaccine exhibits weak immunogenicity, which limits its effectiveness in preventing and controlling influenza virus infections. Methods: In this study, we aimed to develop a T4 phage-based nanovaccine designed to enhance the immunogenicity of two antigens by displaying the HA1 and M2e antigens of the H3N2 influenza virus on each phage nanoparticle. Specifically, we fused the Soc protein with the HA1 antigen and the Hoc protein with the M2e antigen, assembling them onto a T4 phage that lacks Soc and Hoc proteins (Soc−Hoc−T4), thereby constructing a nanovaccine that concurrently presents both HA1 and M2e antigens. Results: The analysis of the optical density of the target protein bands indicated that each particle could display approximately 179 HA1 and 68 M2e antigen molecules. Additionally, animal experiments demonstrated that this nanoparticle vaccine displaying dual antigen clusters induced a stronger specific immune response, higher antibody titers, a more balanced Th1/Th2 immune response, and enhanced CD4+ and CD8+ T cell effects compared to immunization with HA1 and M2e antigen molecules alone. Importantly, mice immunized with the T4 phage displaying dual antigen clusters achieved full protection (100% protection) against the H3N2 influenza virus, highlighting its robust protective efficacy. Conclusions: In summary, our findings indicate that particles based on a T4 phage displaying antigen clusters exhibit ideal immunogenicity and protective effects, providing a promising strategy for the development of subunit vaccines against various viruses beyond influenza. Full article
(This article belongs to the Special Issue Next-Generation Vaccines for Animal Infectious Diseases)
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25 pages, 876 KiB  
Review
Efficacy of Anti-Cancer Immune Responses Elicited Using Tumor-Targeted IL-2 Cytokine and Its Derivatives in Combined Preclinical Therapies
by Sahar Balkhi, Giorgia Bilato, Andrea De Lerma Barbaro, Paola Orecchia, Alessandro Poggi and Lorenzo Mortara
Vaccines 2025, 13(1), 69; https://doi.org/10.3390/vaccines13010069 - 13 Jan 2025
Viewed by 748
Abstract
Effective cancer therapies must address the tumor microenvironment (TME), a complex network of tumor cells and stromal components, including endothelial, immune, and mesenchymal cells. Durable outcomes require targeting both tumor cells and the TME while minimizing systemic toxicity. Interleukin-2 (IL-2)-based therapies have shown [...] Read more.
Effective cancer therapies must address the tumor microenvironment (TME), a complex network of tumor cells and stromal components, including endothelial, immune, and mesenchymal cells. Durable outcomes require targeting both tumor cells and the TME while minimizing systemic toxicity. Interleukin-2 (IL-2)-based therapies have shown efficacy in cancers such as metastatic melanoma and renal cell carcinoma but are limited by severe side effects. Innovative IL-2-based immunotherapeutic approaches include immunotoxins, such as antibody–drug conjugates, immunocytokines, and antibody–cytokine fusion proteins that enhance tumor-specific delivery. These strategies activate cytotoxic CD8+ T lymphocytes and natural killer (NK) cells, eliciting a potent Th1-mediated anti-tumor response. Modified IL-2 variants with reduced Treg cell activity further improve specificity and reduce immunosuppression. Additionally, IL-2 conjugates with peptides or anti-angiogenic agents offer improved therapeutic profiles. Combining IL-2-based therapies with immune checkpoint inhibitors (ICIs), anti-angiogenic agents, or radiotherapy has demonstrated synergistic potential. Preclinical and clinical studies highlight reduced toxicity and enhanced anti-tumor efficacy, overcoming TME-driven immune suppression. These approaches mitigate the limitations of high-dose soluble IL-2 therapy, promoting immune activation and minimizing adverse effects. This review critically explores advances in IL-2-based therapies, focusing on immunotoxins, immunocytokines, and IL-2 derivatives. Emphasis is placed on their role in combination strategies, showcasing their potential to target the TME and improve clinical outcomes effectively. Also, the use of IL-2 immunocytokines in “in situ” vaccination to relieve the immunosuppression of the TME is discussed. Full article
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12 pages, 2225 KiB  
Brief Report
Development and Evaluation of the Immunogenic Potential of an Unmodified Nucleoside mRNA Vaccine for Herpes Zoster
by Shun Zhang, Xiaojie Wang, Tongyi Zhao, Chen Yang and Lulu Huang
Vaccines 2025, 13(1), 68; https://doi.org/10.3390/vaccines13010068 - 13 Jan 2025
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Abstract
Background/Objectives: Approved mRNA vaccines commonly use sequences modified with pseudouridine to enhance translation efficiency and mRNA stability. However, this modification can result in ribosomal frameshifts, reduced immunogenicity, and higher production costs. This study aimed to explore the potential of unmodified mRNA sequences for [...] Read more.
Background/Objectives: Approved mRNA vaccines commonly use sequences modified with pseudouridine to enhance translation efficiency and mRNA stability. However, this modification can result in ribosomal frameshifts, reduced immunogenicity, and higher production costs. This study aimed to explore the potential of unmodified mRNA sequences for varicella-zoster virus (VZV) and evaluate whether codon optimization could overcome the limitations of pseudouridine modification. Methods: We utilized artificial intelligence (AI) to design several unmodified gE mRNA sequences for VZV, considering factors such as codon preference and secondary structure. The optimized mRNA sequences were assessed for protein expression levels in vitro and were subsequently used to develop a vaccine, named Vac07, encapsulated in a lipid nanoparticle (LNP) delivery system. The immunogenicity of Vac07 was evaluated in mice. Results: Codon-optimized mRNA sequences showed significantly higher protein expression levels in vitro compared to wild-type (WT) sequences. Vaccination with Vac07 demonstrated immunogenicity in mice that was comparable to, or even superior to, the licensed Shingrix vaccine, characterized by a stronger Th1-biased antibody response and a slightly more robust Th1-type cellular response. Conclusions: Codon-optimized unmodified mRNA sequences may also represent a viable approach for mRNA vaccine development. These optimized sequences have the potential to lower production costs while possibly enhancing the immunogenicity of mRNA vaccines. Vac07, developed using this method, shows promise as a potentially more efficient and cost-effective mRNA vaccine candidate for VZV. Full article
(This article belongs to the Special Issue Evaluating the Immune Response to RNA Vaccine)
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13 pages, 867 KiB  
Article
Comparing Antibody Responses to Homologous vs. Heterologous COVID-19 Vaccination: A Cross-Sectional Analysis in an Urban Bangladeshi Population
by Kazi Istiaque Sanin, Mansura Khanam, Azizur Rahman Sharaque, Mahbub Elahi, Bharati Rani Roy, Md. Khaledul Hasan, Goutam Kumar Dutta, Abir Dutta, Md. Nazmul Islam, Md. Safiqul Islam, Md. Nasir Ahmed Khan, Mustufa Mahmud, Nuzhat Nadia, Fablina Noushin, Anjan Kumar Roy, Protim Sarker and Fahmida Tofail
Vaccines 2025, 13(1), 67; https://doi.org/10.3390/vaccines13010067 - 13 Jan 2025
Viewed by 635
Abstract
Background: Vaccination has played a crucial role in mitigating the spread of COVID-19 and reducing its severe outcomes. While over 90% of Bangladesh’s population has received at least one COVID-19 vaccine dose, the comparative effectiveness of homologous versus heterologous booster strategies, along with [...] Read more.
Background: Vaccination has played a crucial role in mitigating the spread of COVID-19 and reducing its severe outcomes. While over 90% of Bangladesh’s population has received at least one COVID-19 vaccine dose, the comparative effectiveness of homologous versus heterologous booster strategies, along with the complex interplay of factors within the population, remains understudied. This study aimed to compare antibody responses between these booster approaches. Methods: This cross-sectional study enrolled 723 adults in urban Dhaka who had received COVID-19 booster doses within the last six months. Participants were grouped based on homologous or heterologous booster vaccination. Data were collected through structured household surveys, and 2 mL blood samples were collected for measuring antibody titers. Results: Heterologous booster recipients showed higher median antibody titers (8597.0 U/mL, IQR 5053.0–15,482.3) compared to homologous recipients (6958.0 U/mL, IQR 3974.0–12,728.5). In the adjusted analysis, the type of booster dose had no significant impact on antibody levels. However, the duration since the last booster dose was significantly associated with antibody levels, where each additional month since receiving the booster corresponded to approximately a 15–16% reduction in antibody levels (Adj. coeff: 0.85, 95% CI: 0.81, 0.88; p < 0.001). Participants over 40 years demonstrated higher antibody levels than younger individuals (Adj. coeff: 1.23, 95% CI: 1.07, 1.43; p = 0.005). Sex, BMI, and prior COVID-19 infection showed no significant associations with antibody levels after adjustment. Conclusion: The results underscore the complexity of immune responses across different demographic groups and suggest potential benefits of ongoing heterologous booster strategies in sustaining immunity. Full article
(This article belongs to the Section COVID-19 Vaccines and Vaccination)
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