Vaccines

13 pages, 1066 KiB

Open AccessArticle

Comparative Study of Two Immunisation Protocols in Goats Using Thiol-Sepharose Chromatography-Enriched Extracts from Adult Haemonchus contortus Worms

by Magnolia M. Conde-Felipe, José Adrián Molina, Antonio Ruiz, Otilia Ferrer, Mª Cristina Del Rio, Emma Carmelo, Juan R. Hernández-Fernaud, Francisco Rodríguez and José Manuel Molina

Vaccines 2025, 13(7), 708; https://doi.org/10.3390/vaccines13070708 (registering DOI) - 29 Jun 2025

Abstract

Background: A comparative analysis was conducted between two immunisation protocols using different amounts of protein extracts from adult Haemonchus contortus worms, purified by thiol-Sepharose chromatography (625 μg/animal vs. 200 μg/animal). These protocols involved either five or two inoculations of the immunogen, respectively. [...] Read more.

Background: A comparative analysis was conducted between two immunisation protocols using different amounts of protein extracts from adult Haemonchus contortus worms, purified by thiol-Sepharose chromatography (625 μg/animal vs. 200 μg/animal). These protocols involved either five or two inoculations of the immunogen, respectively. Methods: To evaluate the level of immunoprotection, animals were challenged with L3 of H. contortus two weeks after the last inoculation of the immunogen and humanely sacrificed at 8 weeks post-infection. Parasitological, biopathological, and serological parameters were monitored through the experiment. Parasite burden, abomasal-specific antibody responses, and histopathological changes were determined at the end of the trial. Results: The immunisation protocols resulted in similar reductions in cumulative faecal egg counts (60.5–64.9%) and the total worm burden (47.5–50%) compared to non-immunized (control) animals. Overall, these parasitological data showed an early recovery of the haematocrit (PCV) after challenge in the immunised groups relative to control. Similarly, levels of H. contortus-specific IgG and IgA antibodies increased in both the serum and gastric mucus of immunised groups. Conclusions: These findings represent a further step towards the potential application of this type of immunogen under field conditions, as protective responses (associated with a reduction in faecal egg output) were achieved using a simplified protocol, with lower immunogen doses and fewer inoculations required to induce immunoprotection, thereby mitigating the pathological effects of the parasite and reducing its ability to spread and infect susceptible hosts. Full article

(This article belongs to the Special Issue Infectious Diseases and Immunization in Animals)

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18 pages, 652 KiB

Open AccessArticle

Nasopharyngeal Carriage, Serotype Distribution, and Antimicrobial Susceptibility of Streptococcus pneumoniae Among PCV13-Vaccinated and -Unvaccinated Children in Iran

by Fatemeh Ashrafian, Mona Sadat Larijani, Saiedeh Haji Maghsoudi, Delaram Doroud, Alireza Fahimzad, Zahra Pournasiri, Elham Jafari, Masoumeh Parzadeh, Sara Abdollahi, Elham Haj Agha Gholizadeh Khiavi, Anahita Bavand, Morvarid Shafiei, Mahdi Rohani and Amitis Ramezani

Vaccines 2025, 13(7), 707; https://doi.org/10.3390/vaccines13070707 (registering DOI) - 29 Jun 2025

Abstract

Background and Aim: Pneumococcal pneumonia is a major cause of death globally, emphasizing the importance of vaccination, especially in low- and middle-income countries. In Iran, the 13-valent pneumococcal conjugate vaccine (PCV13) is available exclusively through private healthcare systems, resulting in a lack [...] Read more.

Background and Aim: Pneumococcal pneumonia is a major cause of death globally, emphasizing the importance of vaccination, especially in low- and middle-income countries. In Iran, the 13-valent pneumococcal conjugate vaccine (PCV13) is available exclusively through private healthcare systems, resulting in a lack of studies on the prevalence of Streptococcus pneumoniae (S. pneumoniae) serotypes among vaccinated children. This research aimed to explore and compare the prevalence of nasopharyngeal pneumococcal carriage, serotype distribution, and antibiotic resistance patterns in healthy PCV13-vaccinated and -unvaccinated children. Methods: From August 2023 to November 2024, a multi-center, cross-sectional observational study was conducted in Tehran, Iran. This study included 204 nasopharyngeal samples collected from children aged from 18 to 59 months, involving both cases of children vaccinated with PCV13 and unvaccinated populations. S. pneumoniae was identified through a combination of culture methods and biochemical tests, confirmed by real-time PCR. Serotyping was achieved using cpsB sequencing, and the minimum inhibitory concentration method was employed to assess antibiotic resistance. Results: This study revealed similar S. pneumoniae carriage rates between PCV13-vaccinated and -unvaccinated Iranian children (20.6% vs. 21.6%). Serotypes 23F and 19F were prevalent in unvaccinated children, while 15B/15C was more prevalent in PCV13-vaccinated children. The included S. pneumoniae serotypes in PCV13 were detected more in the unvaccinated group. PCV13-vaccinated children exhibited no penicillin-resistant pneumococcal isolates, although four isolates were non-susceptible in unvaccinated children. Both groups showed substantial resistance to erythromycin and SXT. Previous respiratory infections, daycare attendance, residence in Tehran, and a history of antibiotic consumption increased the risk of pneumococcal carriage. Conclusions: PCV13 vaccination influences pneumococcal serotype distribution and antimicrobial susceptibility, although there was no significant difference regarding carriage rates between vaccinated and unvaccinated groups. These findings highlight the critical importance of vaccination in reducing invasive serotypes and antimicrobial resistance in children under five years old, emphasizing the importance of national PCV vaccination programs alongside continuous serotype surveillance. Full article

(This article belongs to the Section Epidemiology)

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17 pages, 933 KiB

Open AccessArticle

BCG Vaccination Potentially Modulates the Transcriptome of Infant CD4 T Cells in Addition to Age-Dependent Immune Ontogeny-Associated Changes

by Vidya Vijayan Karuvan Kandiyil, Eunchong Kang, Emily Coates, Portia Kamthunzi, Gerald Tegha, Mina Hosseinipour, Di Wu, Fei Zou and Kristina De Paris

Vaccines 2025, 13(7), 706; https://doi.org/10.3390/vaccines13070706 (registering DOI) - 29 Jun 2025

Abstract

Background: The Bacille Calmette–Guérin (BCG) vaccine is part of the Extended Programme on Immunization (EPI) and as such is generally administered at birth. The global introduction of BCG not only protected many vaccinated infants against severe complications of tuberculosis but also resulted in [...] Read more.

Background: The Bacille Calmette–Guérin (BCG) vaccine is part of the Extended Programme on Immunization (EPI) and as such is generally administered at birth. The global introduction of BCG not only protected many vaccinated infants against severe complications of tuberculosis but also resulted in markedly reduced overall childhood mortality. Studies in human adults determined that BCG vaccination induces epigenetic reprogramming of innate immune cells (also known as trained immunity) and can also enhance T cell responses to both mycobacterial and non-mycobacterial antigens. Goal and Methods: The current study tested the hypothesis that BCG immunization similarly impacts the functionally distinct infant immune system. Towards this goal, we applied RNA sequencing to assess transcriptome changes in circulating CD4⁺ T cells of Malawian infants prior to and 2 to 13 weeks after BCG immunization. Results: In the first three months of life, transcriptome changes of infant CD4 T cells implied a functional shift towards T helper 1 and Th17 immunity. Vaccination with BCG resulted in additional modulation of the CD4 T cell transcriptome and differentially expressed genes could be linked to metabolomic function. Conclusions: These findings are consistent with data reported in BCG vaccinated adults and contribute to the understanding of molecular changes in infant CD4 T cells that may explain the improved capacity of the infant immune system to respond to pathogens after BCG vaccination. Full article

(This article belongs to the Section Attenuated/Inactivated/Live and Vectored Vaccines)

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14 pages, 1463 KiB

Open AccessArticle

Influenza Vaccination Coverage Among Elderly Patients with Chronic Lung Respiratory Disease in Ningbo, China: Impact of Free Vaccination Policies and the COVID-19 Pandemic

by Xiaoqing Wu, Jieping Chen, Pingping Li, Tianchi Yang and Lixia Ye

Vaccines 2025, 13(7), 705; https://doi.org/10.3390/vaccines13070705 (registering DOI) - 29 Jun 2025

Abstract

Background: Elderly patients with chronic lower respiratory diseases (CLRDs) demonstrate an increased susceptibility to complications arising from influenza. Influenza vaccination remains the most effective strategy against influenza-related diseases among elderly CLRD patients. This study aimed to evaluate the influenza vaccination status of older [...] Read more.

Background: Elderly patients with chronic lower respiratory diseases (CLRDs) demonstrate an increased susceptibility to complications arising from influenza. Influenza vaccination remains the most effective strategy against influenza-related diseases among elderly CLRD patients. This study aimed to evaluate the influenza vaccination status of older CLRD patients and the factors affecting influenza vaccination. Methods: Using population-based health registries, we analyzed the longitudinal uptake of influenza vaccination among elderly patients with CLRDs in Ningbo from the 2018/19 season to the 2022/23 season. A multivariate logistic regression analysis was performed to identify behavioral determinants influencing influenza vaccination among elderly CLRD patients under Ningbo’s post-pandemic free vaccination policy. Results: An average of 487,309 older patients with CLRDs were included in our analysis for each season. The influenza vaccination rate increased from 3.59% in 2018/19 to 43.32% in the 2022/23 influenza season. There was a significant increase in the proportion of timely influenza vaccinations prior to November 15, rising from 3.01% before the COVID-19 pandemic to 33.90% during the pandemic period. The multivariate logistic regression analysis indicated that both the COVID-19 pandemic and free vaccination policy significantly promoted influenza vaccine uptake. Older CLRD patients with comorbidities such as diabetes, hypertension, or cancer exhibited higher influenza vaccination coverage, whereas those who have experienced acute cardiovascular events showed a lower vaccination rate. Additionally, a prior vaccination history significantly influenced uptake. Conclusions: Despite the significant improvement in vaccination rates, coverage among elderly patients with CLRDs remains below the WHO target. Addressing this gap requires integrated interventions that combine expanding the population eligible for free vaccinations, community mobilization efforts, and effective communication regarding cardiovascular safety to mitigate vaccine hesitancy within high-risk groups. Full article

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

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13 pages, 383 KiB

Open AccessArticle

Evaluation of Recombinant Foot-And-Mouth Disease SAT2 Vaccine Strain in Terms of Antigen Productivity, Virus Inactivation Kinetics, and Immunogenicity in Pigs for Domestic Antigen Bank

by Jae Young Kim, Sun Young Park, Gyeongmin Lee, Mijung Kwon, Jong Sook Jin, Jong-Hyeon Park and Young-Joon Ko

Vaccines 2025, 13(7), 704; https://doi.org/10.3390/vaccines13070704 (registering DOI) - 28 Jun 2025

Abstract

Background: Since the massive outbreak of foot-and-mouth disease (FMD) in South Korea in 2010–2011, cloven-hoofed livestock have been immunized with serotype O and A vaccines across the country. Other serotypes of FMD vaccines were stockpiled in overseas FMD vaccine factories as antigen banks. [...] Read more.

Background: Since the massive outbreak of foot-and-mouth disease (FMD) in South Korea in 2010–2011, cloven-hoofed livestock have been immunized with serotype O and A vaccines across the country. Other serotypes of FMD vaccines were stockpiled in overseas FMD vaccine factories as antigen banks. Once a manufacturing facility has been established in South Korea, the overseas antigen banks will be replaced by domestic one. Therefore, this study aimed to evaluate the commercial potential of the previously developed SAT2 vaccine candidate (SAT2 ZIM-R). Methods: The optimal condition was determined at various virus concentrations, infection times, and pH levels, resulting in 0.01 MOI for SAT2 ZIM-R for 24 h infection at a pH of 7.5. Results: When the SAT2 ZIM-R virus was produced in flasks from 40 to 1000 mL in fivefold increments, all scales of production yielded >7.0 µg/mL of antigens. Using a bioreactor, 5.6 µg/mL of antigens was recovered from a 1 L viral culture. The optimal conditions of viral inactivation kinetics were determined to be 1 mM of binary ethyleneimine (BEI) treatment at 26 °C for 24 h, with approximately 91% of the antigen being retained after virus inactivation. When the SAT2 ZIM-R experimental vaccine was administered twice to pigs, the neutralizing antibody titer increased approximately 500-fold after booster immunization. Conclusions: To the best of our knowledge, this is the first study to evaluate the antigen productivity, viral inactivation kinetics, and immunogenicity of the SAT vaccine strain in pigs. In the future, the SAT2 ZIM-R vaccine may be a useful candidate vaccine for a domestic antigen bank. Full article

(This article belongs to the Special Issue Innovations in Vaccine Technology)

15 pages, 535 KiB

Open AccessReview

Recent Advances in Bioconjugate Vaccine Development

by Brendan W. Wren, Catherine L. Hall, Vanessa S. Terra, Mark A. Harrison, Elizabeth Atkins, Fauzy Nasher and Ian J. Passmore

Vaccines 2025, 13(7), 703; https://doi.org/10.3390/vaccines13070703 (registering DOI) - 28 Jun 2025

Abstract

Glycoconjugate vaccines, consisting of a protein component covalently linked to a glycan antigen, have led to a significant reduction in the global occurrence of bacterial meningitis and pneumonia. They provide robust, lasting immunity in all age groups. However, their production by traditional chemical [...] Read more.

Glycoconjugate vaccines, consisting of a protein component covalently linked to a glycan antigen, have led to a significant reduction in the global occurrence of bacterial meningitis and pneumonia. They provide robust, lasting immunity in all age groups. However, their production by traditional chemical conjugation approaches has drawbacks in terms of complexity, cost, and lack of flexibility in design, which explains their limited application to a few pathogenic bacteria in the past four decades. Protein glycan coupling technology (PGCT) or bioconjugation, where glycoconjugates are produced in purpose-engineered bacterial cells, is a useful alternative to chemical conjugation and promises an array of low-cost custom-made glycoconjugate vaccines with vast protein glycan combinations. The technology has undergone significant development since its inception, and new advances and refinements continually drive the field forward. Several bioconjugate vaccines are currently in clinical trials, demonstrating the potential of the technology. We will review the wide applicability of bioconjugation and recent developments in each of the components of the technology, namely, glycan expression, protein selection, and the coupling of selected glycan with proteins, all within custom-designed E. coli cells. These advances promise to deliver effective glycoconjugate vaccines for multiple unmet medical needs. Full article

(This article belongs to the Special Issue The Current Development of Glycoconjugate Vaccines for Infectious Diseases)

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18 pages, 2850 KiB

Open AccessArticle

An mRNA Vaccine Expressing Blood-Stage Malaria Antigens Induces Complete Protection Against Lethal Plasmodium yoelii

by Amy C. Ott, Patrick J. Loll and James M. Burns, Jr.

Vaccines 2025, 13(7), 702; https://doi.org/10.3390/vaccines13070702 (registering DOI) - 28 Jun 2025

Abstract

Background and Objectives: To evaluate the mRNA vaccine platform for blood-stage Plasmodium parasites, we completed a proof-of-concept study using the P. yoelii mouse model of malaria and two mRNA-based vaccines. Both encoded PyMSP1₁₉ fused to PyMSP8 (PyMSP1/8). One [...] Read more.

Background and Objectives: To evaluate the mRNA vaccine platform for blood-stage Plasmodium parasites, we completed a proof-of-concept study using the P. yoelii mouse model of malaria and two mRNA-based vaccines. Both encoded PyMSP1₁₉ fused to PyMSP8 (PyMSP1/8). One was designed for secretion of the encoded protein (PyMSP1/8-sec); the other encoded membrane-bound antigen (PyMSP1/8-mem). Methods: Secretion of PyMSP1/8-sec and membrane localization of PyMSP1/8-mem were verified in mRNA-transfected cells. As recombinant PyMSP1/8 (rPyMSP1/8) is known to protect mice against lethal P. yoelii 17XL infection, we first compared immunogenicity and efficacy of the PyMSP1/8-sec mRNA vaccine versus the recombinant formulation in outbred mice. Animals were immunized three times followed by challenge with a lethal dose of P. yoelii 17XL-parasitized RBCs (pRBCs). Similar immunization and challenge experiments were conducted to compare PyMSP1/8-sec versus PyMSP1/8-mem mRNA vaccines. Results: Immunogenicity of the PyMSP1/8-sec mRNA vaccine was superior to the recombinant formulation, inducing higher antibody titers against both vaccine components. Following challenge with P. yoelii 17XL pRBCs, all PyMSP1/8-sec-immunized animals survived, with 50% of these showing no detectible pRBCs in circulation (<0.01%). In addition, mean peak parasitemia in PyMSP1/8-sec mRNA-immunized mice was significantly lower than that in the rPyMSP1/8 vaccine group. Both PyMSP1/8-sec and PyMSP1/8-mem were protective against P. yoelii 17XL challenge, with PyMSP1/8-mem immunization providing a significantly higher level of protection than PyMSP1/8-sec immunization considering the number of animals with no detectable pRBCs in circulation and the mean peak parasitemia in animals with detectable parasitemia. Conclusions: mRNA vaccines were highly immunogenic and potently protective against blood-stage malaria, outperforming a similar recombinant-based vaccine. The membrane-bound antigen was more effective at inducing protective antibody responses, highlighting the need to consider antigen localization for mRNA vaccine design. Full article

(This article belongs to the Special Issue Vaccination Against Vector-Borne Diseases: Bridging Public Health and Epidemiology)

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19 pages, 3465 KiB

Open AccessArticle

Immunogenicity of Matrix Protein 2 Ectodomain (M2e) Displayed on Nodavirus-Like Particles as Avian Influenza Vaccine for Poultry

by Anis Suraya Mohamad Abir, Wen Siang Tan, Abdul Rahman Omar, Kok Lian Ho, Munir Iqbal and Abdul Razak Mariatulqabtiah

Vaccines 2025, 13(7), 701; https://doi.org/10.3390/vaccines13070701 (registering DOI) - 27 Jun 2025

Abstract

Avian influenza is an economically significant disease affecting poultry worldwide and is caused by influenza A viruses that can range from low to highly pathogenic strains. These viruses primarily target the respiratory, digestive, and nervous systems of birds, leading to severe outbreaks that [...] Read more.

Avian influenza is an economically significant disease affecting poultry worldwide and is caused by influenza A viruses that can range from low to highly pathogenic strains. These viruses primarily target the respiratory, digestive, and nervous systems of birds, leading to severe outbreaks that threaten poultry production and pose zoonotic risks. The ectodomain of the avian influenza virus (AIV) matrix protein 2 (M2e), known for its high conservation across influenza strains, has emerged as a promising candidate for developing a universal influenza vaccine in a mouse model. However, the efficacy of such expression against poultry AIVs remains limited. The objective of this study was to evaluate the immunogenicity of nodavirus-like particles displaying the M2e proteins. In this study, three synthetic heterologous M2e genes originated from AIV strains H5N1, H9N2 and H5N2 were fused with the nodavirus capsid protein (NVC) of the giant freshwater prawn Macrobrachium rosenbergii (NVC-3xAvM2e) prior to immunogenicity characterisations in chickens. The expression vector pTRcHis-TARNA2 carrying the NVC-3xAvM2e gene cassette was introduced into E. coli TOP-10 cells. The recombinant proteins were purified, inoculated into one-week-old specific pathogen-free chickens subcutaneously and analysed. The recombinant protein NVC-3xAvM2e formed virus-like particles (VLPs) of approximately 25 nm in diameter when observed under a transmission electron microscope. Dynamic light scattering (DLS) analysis revealed that the VLPs have a polydispersity index (PDI) of 0.198. A direct ELISA upon animal experiments showed that M2e-specific antibodies were significantly increased in vaccinated chickens after the booster, with H5N1 M2e peptides having the highest mean absorbance value when compared with those of H9N2 and H5N2. A challenge study using low pathogenic AIV (LPAI) strain A/chicken/Malaysia/UPM994/2018 (H9N2) at 10^6.5 EID₅₀ showed significant viral load in the lung and cloaca, but not in the oropharyngeal of vaccinated animals when compared with the unvaccinated control group. Collectively, this study suggests that nodavirus-like particles displaying three heterologous M2e have the potential to provide protection against LPAI H9N2 in chickens, though the vaccine’s efficacy and cross-protection across different haemagglutinin (HA) subtypes should be further evaluated. Full article

(This article belongs to the Special Issue Veterinary Vaccines and Host Immune Responses)

20 pages, 497 KiB

Open AccessArticle

Seroprevalence of Measles-, Mumps-, and Rubella-Specific Antibodies in Future Healthcare Workers in Serbia: A Cross-Sectional Study

by Ana Banko, Andja Cirkovic, Vladimir Petrovic, Mioljub Ristic, Vladimir Vukovic, Dobrila Stankovic-Djordjevic and Danijela Miljanovic

Vaccines 2025, 13(7), 700; https://doi.org/10.3390/vaccines13070700 (registering DOI) - 27 Jun 2025

Abstract

Background/Objectives: Measles, mumps, and rubella (MMR) continue to pose a significant public health challenge due to insufficient immunization coverage. This study aimed to provide the first seroprevalence data against MMR and to explore self-reported immunity among future healthcare workers (HCWs) in Serbia, including [...] Read more.

Background/Objectives: Measles, mumps, and rubella (MMR) continue to pose a significant public health challenge due to insufficient immunization coverage. This study aimed to provide the first seroprevalence data against MMR and to explore self-reported immunity among future healthcare workers (HCWs) in Serbia, including women of childbearing age. Methods: We included 1296 future health care workers (HCWs) aged 19 to 29, born in Serbia. All HCWs supplied a blood sample for serology and filled in a questionnaire. Antibodies were measured using an enzyme immunoassay against measles, mumps, and rubella (MMR). Results: Anti-measles, -mumps, and -rubella seronegativity rates were 25.6%, 26.5%, and 4.4%, respectively, among future HCWs in Serbia. The mumps seronegativity rate was significantly higher in the oldest (27–29-year) age group, accompanied by significantly lower anti-mumps IgG GMCs in the same age group compared to younger participants (p = 0.035 and p < 0.001, respectively). Anti-mumps seronegativity also increased significantly across birth cohorts, from the youngest to the oldest (p = 0.004). Furthermore, anti-mumps IgG antibody GMCs were significantly higher among females, those who attended nursery/kindergarten, and unvaccinated individuals (p = 0.050, p = 0.020, and p = 0.005, respectively). Finally, older age and unvaccinated status were identified as independent factors associated with anti-measles and anti-mumps seronegativity among future HCWs in Serbia. Conclusions: The cross-sectional seroprevalence data revealed insufficient seroprotection in this population of particular importance, i.e., future HCWs, and women of childbearing age. These results strongly support the national recommendations for the mandatory vaccination of these populations. Identified immunity gaps should be closed promptly by strategic, targeted serologic screening, followed by vaccination of those lacking MMR antibodies. Full article

(This article belongs to the Special Issue Vaccines and Immunization: Measles, Mumps, and Rubella)

20 pages, 495 KiB

Open AccessArticle

Exploring Vaccine Hesitancy, Structural Barriers, and Trust in Vaccine Information Among Populations Living in the Rural Southern United States

by Alice R. Richman, Abby J. Schwartz, Sarah B. Maness, Leslie Sanchez and Essie Torres

Vaccines 2025, 13(7), 699; https://doi.org/10.3390/vaccines13070699 (registering DOI) - 27 Jun 2025

Abstract

Introduction: In the United States, vaccine hesitancy is higher among rural and racially and ethnically diverse communities, and messaging from trusted individuals may increase vaccine acceptance. The purpose of this study is to understand vaccine hesitancy, messaging from trusted individuals, and vaccine acceptance [...] Read more.

Introduction: In the United States, vaccine hesitancy is higher among rural and racially and ethnically diverse communities, and messaging from trusted individuals may increase vaccine acceptance. The purpose of this study is to understand vaccine hesitancy, messaging from trusted individuals, and vaccine acceptance strategies among racially and ethnically diverse, medically underserved rural populations. Methods: The researchers conducted 12 in-person focus groups, each consisting of 5 to 12 participants, with community members and trusted leaders from three rural counties in Eastern North Carolina (n = 119). Thematic analysis was used to synthesize insights from the discussions, allowing for the identification of recurring patterns and community-specific considerations regarding vaccine perceptions and messaging. Results: The researchers identified seven key themes within the primary focus areas of the study: factors influencing vaccine hesitancy, messaging from trusted individuals, and strategies to improve vaccine acceptance. Participants reported differences in trust based on how long a vaccine has been available, concerns about becoming sick after a vaccine, seeing the symptoms of vaccine-preventable diseases, and misinformation on social media. Overall, participants reported trust in messages from medical providers. Trusted leaders advised people to conduct their own research on vaccines when determining whether to receive vaccinations. Lastly, social determinants such as cost, education, and transportation were identified as key barriers to vaccination. Conclusions: Our findings indicate that medical providers are trusted messengers for vaccine information and the promotion of vaccine uptake. However, distrust linked to fear, misinformation, and structural barriers persist. Public health efforts to increase vaccination confidence among rural, racially and ethnically diverse populations in the United States Southeast should address these factors in future vaccine interventions and educational efforts. Full article

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

17 pages, 619 KiB

Open AccessArticle

Impact of Prior SARS-CoV-2 Infection on COVID-19 Vaccine Effectiveness in Children and Adolescents in Norway and Italy

by Elisa Barbieri, Nhung T. H. Trinh, Costanza Di Chiara, Giovanni Corrao, Riccardo Boracchini, Ester Rosa, Cecilia Liberati, Daniele Donà, Angela Lupattelli, Carlo Giaquinto and Anna Cantarutti

Vaccines 2025, 13(7), 698; https://doi.org/10.3390/vaccines13070698 (registering DOI) - 27 Jun 2025

Abstract

^‡ These authors contributed equally to this work as co-senior authors [...] Full article

(This article belongs to the Special Issue Advance Public Health Through Vaccination)

15 pages, 796 KiB

Open AccessArticle

A Novel, Safe, Non-Adjuvanted Alphavirus Replicon-Based Vaccine Expressing the Feline Leukemia Virus Envelope Protein Protects Against Virulent FeLV Challenge

by Kari Carritt, Randall Davis, Ken Stachura, Paige Crumley, Mark Mogler, Madeleine Stahl, Lijuan Deng, Zach Xu and Ian Tarpey

Vaccines 2025, 13(7), 697; https://doi.org/10.3390/vaccines13070697 (registering DOI) - 27 Jun 2025

Abstract

Background/Objectives: A number of different vaccines against feline leukemia virus (FeLV) are available; however, there is continuous debate regarding the efficacy advantages of adjuvanted vaccines versus the potential safety advantages of non-adjuvanted vaccines. Methods: For this reason, we developed a non-adjuvanted vaccine based [...] Read more.

Background/Objectives: A number of different vaccines against feline leukemia virus (FeLV) are available; however, there is continuous debate regarding the efficacy advantages of adjuvanted vaccines versus the potential safety advantages of non-adjuvanted vaccines. Methods: For this reason, we developed a non-adjuvanted vaccine based on a replicon RNA particle (RP) expressing the FeLV gp85 envelope protein, which possesses the safety of a non-adjuvanted vaccine while consistently providing high efficacy. Results: In two efficacy studies, a high-level of protection against virulent FeLV challenge was demonstrated with two doses given 3 weeks apart based on the prevention of FeLV p27 antigenemia. Furthermore, in both studies, we compared this novel vaccine against a non-adjuvanted, canarypox-vectored FeLV vaccine, demonstrating that none of the cats that received two doses of the RP-FeLV vaccine developed persistent antigenemia post-challenge. In comparison, of cats receiving the canarypox-vectored FeLV vaccine, three of seven (43%) became persistently antigenemic in one study, and three of ten (30%) became persistently antigenemic in the other study. In a field safety study using two commercial serials, safety of the RP-FeLV vaccine was demonstrated in over 800 cats receiving two doses of the vaccine. Conclusions: These data suggest that the RP-FeLV vaccine offers advantages over some current FeLV vaccines by combining the safety profile of a non-adjuvanted vaccine with the induction of a robust immune response demonstrated by some adjuvanted vaccines. Full article

(This article belongs to the Section Veterinary Vaccines)

21 pages, 1651 KiB

Open AccessArticle

ISG15 as a Potent Immune Adjuvant in MVA-Based Vaccines Against Zika Virus and SARS-CoV-2

by Juan García-Arriaza, Michela Falqui, Patricia Pérez, Rocío Coloma, Beatriz Perdiguero, Enrique Álvarez, Laura Marcos-Villar, David Astorgano, Irene Campaña-Gómez, Carlos Óscar S. Sorzano, Mariano Esteban, Carmen Elena Gómez and Susana Guerra

Vaccines 2025, 13(7), 696; https://doi.org/10.3390/vaccines13070696 (registering DOI) - 27 Jun 2025

Abstract

Background: Vaccines represent one of the most affordable and efficient tools for controlling infectious diseases; however, the development of efficacious vaccines against complex pathogens remains a major challenge. Adjuvants play a relevant role in enhancing vaccine-induced immune responses. One such molecule is interferon-stimulated [...] Read more.

Background: Vaccines represent one of the most affordable and efficient tools for controlling infectious diseases; however, the development of efficacious vaccines against complex pathogens remains a major challenge. Adjuvants play a relevant role in enhancing vaccine-induced immune responses. One such molecule is interferon-stimulated gene 15 (ISG15), a key modulator of antiviral immunity that acts both through ISGylation-dependent mechanisms and as a cytokine-like molecule. Methods: In this study, we assessed the immunostimulatory potential of ISG15 as an adjuvant in Modified Vaccinia virus Ankara (MVA)-based vaccine candidates targeting Zika virus (ZIKV) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Early innate responses and immune cell infiltration were analyzed in immunized mice by flow cytometry and cytokine profiling. To elucidate the underlying mechanism of action of ISG15, in vitro co-infection studies were performed in macrophages. Finally, we evaluated the magnitude and functional quality of the elicited antigen-specific cellular immune responses in vivo. Results: Analysis of early innate responses revealed both platform- and variant-specific effects. ISG15AA preferentially promoted natural killer (NK) cell recruitment at the injection site, whereas ISG15GG enhanced myeloid cell infiltration in draining lymph nodes (DLNs), particularly when delivered via MVA. Moreover, in vitro co-infection of macrophages with MVA-based vaccine vectors and the ISG15AA mutant led to a marked increase in proinflammatory cytokine production, highlighting a dominant role for the extracellular, ISGylation-independent functions of ISG15 in shaping vaccine-induced immunity. Notably, co-infection of ISG15 with MVA-ZIKV and MVA-SARS-CoV-2 vaccine candidates enhanced the magnitude of antigen-specific immune responses in both vaccine models. Conclusions: ISG15, particularly in its ISGylation-deficient form, acts as a promising immunomodulatory adjuvant for viral vaccines, enhancing both innate and adaptive immune responses. Consistent with previous findings in the context of Human Immunodeficiency virus type 1 (HIV-1) vaccines, this study further supports the potential of ISG15 as an effective adjuvant for vaccines targeting viral infections such as ZIKV and SARS-CoV-2. Full article

(This article belongs to the Special Issue Protective Immunity and Adjuvant Vaccines)

11 pages, 2696 KiB

Open AccessArticle

The Baculovirus Expression System Expresses Chimeric RHDV VLPs as Bivalent Vaccine Candidates for Classic RHDV (GI.1) and RHDV2 (GI.2)

by Yan Wang, Yiyang Fan, Ruixiang Bi, Yapeng Zhao, Wanning Gao, Derong Zhang and Jialin Bai

Vaccines 2025, 13(7), 695; https://doi.org/10.3390/vaccines13070695 (registering DOI) - 27 Jun 2025

Abstract

Background: Rabbit hemorrhagic disease (RHD) is an acute, hemorrhagic and highly lethal infectious disease caused by rabbit hemorrhagic disease virus (RHDV), which causes huge economic losses to the rabbit breeding industry. Moreover, there is limited cross-protection between the two different serotypes of classic [...] Read more.

Background: Rabbit hemorrhagic disease (RHD) is an acute, hemorrhagic and highly lethal infectious disease caused by rabbit hemorrhagic disease virus (RHDV), which causes huge economic losses to the rabbit breeding industry. Moreover, there is limited cross-protection between the two different serotypes of classic RHDV (GI.1) and RHDV2 (GI.2). The shortcomings of traditional inactivated vaccines have led to the development of novel subunit vaccines that can protect against both strains, and the VP60 capsid protein is the ideal antigenic protein. This study focused on developing a bivalent RHDV vaccine that can prevent infection with both GI.1 and GI.2 strains. Methodology: Baculovirus vectors containing classic RHDV and RHDV2 VP60 were co-transfected with linearized baculovirus into sf9 cells and transferred to baculovirus via homologous recombination of the VP60 gene. Infected sf9 cells were lysed, and after purification via Ni-NTA chromatography, VLPs were observed using transmission electron microscopy (TEM). In order to evaluate the immunogenicity of the chimeric RHDV VLP vaccine in rabbits, the RHDV VP60-specific antibody, IL-4, IFN-γ and neutralizing antibody titers were analyzed in serum using ELISA and HI. Results: The recombinant baculovirus system successfully expressed chimeric RHDV VLPs with a diameter of 32–40 nm. After immunization, it could produce specific antibodies, IL-4 and IFN-γ. Following the second immunization, neutralizing antibodies, determined using hemagglutination inhibition (HI) assays, were elicited. Conclusions: These data show that the chimeric RHDV VLP bivalent vaccine for immunized New Zealand rabbits can induce humoral immunity and cellular immunity in vivo, and the immunization effect of the high-dose group is similar to that of the current commercial vaccine. Full article

(This article belongs to the Section Veterinary Vaccines)

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17 pages, 5747 KiB

Open AccessArticle

Proteomic Profiling of Human Peripheral Blood Cell Targets of IgG Induced by SARS-CoV-2: Insights into Vaccine Safety

by Nicolle Rakanidis Machado, Lais Alves do Nascimento, Beatriz Oliveira Fagundes, João Vitor da Silva Borges, Fabio da Ressureição Sgnotto, Isabella Siuffi Bergamasco, Juliana Ruiz Fernandes, Thalyta Nery Carvalho Pinto, Anna Julia Pietrobon, Gil Benard, Maria Notomi Sato and Jefferson Russo Victor

Vaccines 2025, 13(7), 694; https://doi.org/10.3390/vaccines13070694 (registering DOI) - 27 Jun 2025

Abstract

Background/Objectives: COVID-19 has been associated with a wide range of immune responses, including the production of autoantibodies, particularly in severe cases. This study investigates the IgG autoantibody responses in patients with varying severities of COVID-19 infection and compares these responses with vaccinated individuals. [...] Read more.

Background/Objectives: COVID-19 has been associated with a wide range of immune responses, including the production of autoantibodies, particularly in severe cases. This study investigates the IgG autoantibody responses in patients with varying severities of COVID-19 infection and compares these responses with vaccinated individuals. Methods: We utilized proteomic profiling to analyze autoantibody reactivity against a broad spectrum of proteins expressed in lymphoid and myeloid cell subsets in serum samples from severe and moderate COVID-19 patients, as well as vaccinated individuals who received the inactivated CoronaVac (Sinovac) vaccine. Results: Our findings indicate a marked increase in the diversity and number of IgG autoantibodies targeting intracellular and membrane-associated proteins in severe COVID-19 cases, compared to those with moderate cases of the disease. The autoantibody response in severe cases was found to primarily target proteins involved in immune cell activation, signaling, and differentiation, suggesting potential pathways of immune dysregulation and autoimmunity. In contrast, vaccinated individuals did not exhibit similar autoantibody reactivity, pointing to a more controlled immune response post-vaccination. Notably, no significant autoimmune responses were detected in the vaccinated cohort, suggesting that the inactivated vaccine does not induce autoreactive IgG. These findings align with the established safety profile of COVID-19 vaccines, especially in comparison to the heightened immune dysregulation observed in severe COVID-19 patients. The absence of a significant autoantibody response in vaccinated individuals supports the notion that vaccines, while inducing robust immune activation, do not typically trigger autoimmunity in healthy individuals. Conclusions: Our study underscores the importance of distinguishing between the immune responses triggered by infection and vaccination and highlights the need for the continued monitoring of autoimmune responses in severe COVID-19 cases. Future research should focus on the long-term persistence and clinical relevance of these autoantibodies, particularly in individuals with pre-existing autoimmune conditions or genetic predispositions. Full article

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

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20 pages, 3846 KiB

Open AccessArticle

Early to Late VSV-G Expression in AcMNPV BV Enhances Transduction in Mammalian Cells but Does Not Affect Virion Yield in Insect Cells

by Jorge Alejandro Simonin, Franco Uriel Cuccovia Warlet, María del Rosario Bauzá, María del Pilar Plastine, Victoria Alfonso, Fernanda Daniela Olea, Carolina Susana Cerrudo and Mariano Nicolás Belaich

Vaccines 2025, 13(7), 693; https://doi.org/10.3390/vaccines13070693 (registering DOI) - 26 Jun 2025

Abstract

Background/Objectives: Baculoviruses represent promising gene delivery vectors for mammalian systems, combining high safety profiles with substantial cargo capacity. While pseudotyping with vesicular stomatitis virus G-protein (VSV-G) enhances transduction efficiency, optimal expression strategies during the Autographa californica multiple nucleopolyhedrovirus (AcMNPV) infection cycle remain unexplored. [...] Read more.

Background/Objectives: Baculoviruses represent promising gene delivery vectors for mammalian systems, combining high safety profiles with substantial cargo capacity. While pseudotyping with vesicular stomatitis virus G-protein (VSV-G) enhances transduction efficiency, optimal expression strategies during the Autographa californica multiple nucleopolyhedrovirus (AcMNPV) infection cycle remain unexplored. This study investigates how VSV-G expression timing affects pseudotype incorporation into budded virions (BVs) and subsequent transduction efficacy. Methods: Three recombinant AcMNPV constructs were generated, each expressing VSV-G under distinct baculoviral promoters (ie1, gp64, and p10) and GFP via a CMV promoter. VSV-G incorporation was verified by Western blot, while transduction efficiency was quantified in mammalian cell lines (fluorescence microscopy/flow cytometry) and rat hind limbs. Viral productivity was assessed through production kinetics and plaque assays. Results: All the pseudotyped viruses showed significantly enhanced transduction capacity versus controls, strongly correlating with VSV-G incorporation levels. The p10 promoter drove the highest VSV-G expression and transduction efficiency. Crucially, BV production yields and infectivity remained unaffected by VSV-G expression timing. The in vivo results mirrored the cell culture findings, with p10-driven constructs showing greater GFP expression at low doses (10⁴ virions). Conclusions: Strategic VSV-G expression via very late promoters (particularly p10) maximizes baculoviral transduction without compromising production yields. This study establishes a framework for optimizing pseudotyped BV systems, demonstrating that late-phase glycoprotein expression balances high mammalian transduction with preserved insect-cell productivity—a critical advancement for vaccine vector development. Full article

(This article belongs to the Special Issue Viral Vector-Based Vaccines and Therapeutics)

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Graphical abstract

23 pages, 640 KiB

Open AccessReview

Advances in Contraceptive Vaccine Development: A Comprehensive Review

by Wen Gao, Xiaoting Shen, Peipei Li, Chanchan Xiao and Yongxia Wang

Vaccines 2025, 13(7), 692; https://doi.org/10.3390/vaccines13070692 - 26 Jun 2025

Abstract

The issues of uncontrolled global population growth and unintended pregnancies are severe, and the existing contraceptive methods have numerous limitations, making the development of novel contraceptive technologies urgent. Contraceptive vaccines offer a promising alternative to traditional contraception methods. This article reviews the three [...] Read more.

The issues of uncontrolled global population growth and unintended pregnancies are severe, and the existing contraceptive methods have numerous limitations, making the development of novel contraceptive technologies urgent. Contraceptive vaccines offer a promising alternative to traditional contraception methods. This article reviews the three developmental stages of contraceptive vaccines, including early exploration, technical bottlenecks, and innovative development directions in the new era. This article also summarizes the targets of immunocontraception, covering the current research status of contraceptive vaccines targeting sperm production, sperm antigens, oocyte zona pellucida, and gamete outcomes. Furthermore, this article explores the advantages of contraceptive vaccines in terms of efficiency, non-invasiveness, reversibility, and the promotion of gender equality. Challenges associated with clinical translation and real-world implementation are also critically analyzed. Full article

(This article belongs to the Special Issue Advancements in Vaccine Research: Epidemiology, Immunogenicity, Effectiveness and Safety)

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17 pages, 1874 KiB

Open AccessArticle

A Novel Trivalent BVDV mRNA Vaccine Displayed by Virus-like Particles Eliciting Potent and Broad-Spectrum Antibody Responses

by Shi Xu, Jing Li, Mengwei Xu, Yafei Cai, Yingjuan Qian, Rui Liu, Qing He, Caiyi Fei, Aili Wang, Keyue Ruan, Shang Liu, Wei Geng, Xu Gao, Huiling Chen and Tiyun Han

Vaccines 2025, 13(7), 691; https://doi.org/10.3390/vaccines13070691 (registering DOI) - 26 Jun 2025

Abstract

Background/Objectives: Bovine viral diarrhea virus (BVDV) causes significant economic losses in the cattle industry worldwide. The current vaccines have limited efficacy against diverse BVDV genotypes. Currently, multi-antigen target design and nanocarrier display technologies can provide ideas for broad-spectrum and efficient BVDV vaccine [...] Read more.

Background/Objectives: Bovine viral diarrhea virus (BVDV) causes significant economic losses in the cattle industry worldwide. The current vaccines have limited efficacy against diverse BVDV genotypes. Currently, multi-antigen target design and nanocarrier display technologies can provide ideas for broad-spectrum and efficient BVDV vaccine design. Methods: Here we developed a trivalent mRNA vaccine encoding the domains I-II of envelope glycoprotein E2 from three BVDV genotypes (3E2), introduced with bovine IgG1 Fc (bFc), STABILON (hStab), and artificial virus-like particle (ARVLP) containing CD80 transmembrane (TM) domain, FcγRII cytoplasmic domain, and WW domain of ITCH. Then, in vitro expression, in vivo immunogenicity and neutralizing antibody analysis were performed to evaluate the vaccines. Results: The in vitro expression results showed that bFc and hStab dramatically enhanced antigen expression and immunogenicity. In addition, the ARVLP further enhanced the secretion and potency of neutralizing antibodies. Finally, the immunogenicity of the bFc_BVDV_3E2_ARVLP_hStab mRNA vaccine was evaluated in mice, guinea pigs, and lactating goats and high levels of neutralizing antibodies against all three BVDV genotypes were detected. Conclusions: Our trivalent design strategy with bFc, hStab, and ARVLP shows highly efficient expression as well as strong immunogenicity and provides a promising approach for next-generation BVDV vaccines with broader and stronger protection. Full article

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

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21 pages, 323 KiB

Open AccessReview

Progress and Recent Developments in HIV Vaccine Research

by Iris Shim, Lily Rogowski and Vishwanath Venketaraman

Vaccines 2025, 13(7), 690; https://doi.org/10.3390/vaccines13070690 - 26 Jun 2025

Abstract

Background: Human immunodeficiency virus (HIV) remains a global health challenge despite significant advancements in antiretroviral therapy and prevention strategies. Developing a safe and effective vaccine that protects people worldwide has been a major goal, yet the genetic variability and rapid mutation rate of [...] Read more.

Background: Human immunodeficiency virus (HIV) remains a global health challenge despite significant advancements in antiretroviral therapy and prevention strategies. Developing a safe and effective vaccine that protects people worldwide has been a major goal, yet the genetic variability and rapid mutation rate of the virus continue to pose substantial challenges. Methods: In this review paper, we aim to provide a comprehensive review of previous vaccine candidates and the progress made in HIV vaccine clinical trials, spanning from the late 1990s to 2025. PubMed and ClinicalTrials.gov were searched for English-language Phase 1–3 HIV vaccine trials published from 1990 to March 2025. After de-duplication, titles/abstracts and then full texts were screened; trial phase, regimen, immunogenicity, efficacy, and correlates were extracted into a structured spreadsheet. Owing to platform heterogeneity, findings were synthesized narratively and arranged chronologically to trace the evolution of vaccine strategies. Results: Early vaccine trials demonstrated that a protein subunit vaccine failed to protect against infection, revealing the complexity of HIV evasion strategies and shifting the focus to a comprehensive immune response, including both antibody and T-cell responses. Trials evaluating the role of viral vectors in generating cell-mediated immunity were also insufficient, and suggested that targeting T cell response alone was not enough. In 2009, the RV144 trial made a breakthrough by showing partial protection against HIV infection and providing the first indication of efficacy. This partial success influenced subsequent trials, prompting researchers to further explore the complex immune response required for protection and consider combinations of vaccine technologies to achieve robust, long-lasting immunity. Conclusion: Despite setbacks, decades of rigorous efforts have provided significant contributions to HIV vaccine discovery and development, offering hope for preventing and protecting against HIV infection. The field remains active by continuing to advance our understanding of the virus, refining vaccine strategies, and employing novel technologies. Full article

(This article belongs to the Special Issue Advances in HIV Vaccine Development, 2nd Edition)

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