Vaccines

17 pages, 2604 KiB

Open AccessReview

Chronicling the Journey of Pneumococcal Conjugate Vaccine Introduction in India

by Pawan Kumar, Arindam Ray, Amrita Kumari, Abida Sultana, Rhythm Hora, Kapil Singh, Rashmi Mehra, Amanjot Kaur, Seema Singh Koshal, Syed F. Quadri, Shyam Kumar Singh and Arup Deb Roy

Vaccines 2025, 13(4), 432; https://doi.org/10.3390/vaccines13040432 - 21 Apr 2025

Abstract

Background: Globally, pneumonia claims the lives of about 700,000 children under the age of 5 every year. Pneumococcal conjugate vaccine (PCV) was introduced in India phase-wise, beginning in high-burden states, and the rollout was completed nationwide by 2021—representing a major initiative by the [...] Read more.

Background: Globally, pneumonia claims the lives of about 700,000 children under the age of 5 every year. Pneumococcal conjugate vaccine (PCV) was introduced in India phase-wise, beginning in high-burden states, and the rollout was completed nationwide by 2021—representing a major initiative by the Ministry of Health and Family Welfare (MoHFW). Despite the challenges posed by the COVID-19 pandemic, the campaign succeeded in maintaining progress and achieving nationwide coverage. This narrative review highlights the significant decisions, processes, and coordinated efforts of the various stakeholders involved that led to this successful PCV rollout. Methodology: A comprehensive desk review of both published and unpublished literature relevant to pneumonia burden and the efficacy and effectiveness of PCVs, along with documentation of PCV introduction and the scale-up was carried out. Results: The documentation of the PCV journey has been broken down into four sections: pre-introduction, PCV Phase-I introduction, pan-India rapid expansion, and the period post-introduction. Since the nationwide rollout in 2021, PCV coverage in India has steadily increased, reflecting successful immunization efforts. WUENIC, which is an annual WHO, and UNICEF estimates of national immunization coverage also show a positive trend in vaccination coverage (PCV booster coverage = 25% (2021), rising to 83% (2023), aligning with the goals of the WHO and UNICEF’s Global Action Plan for the Prevention and Control of Pneumonia and Diarrhoea (GAPPD). Conclusions: The phased rollout was an ambitious effort by the MoHFW, which was particularly challenging given the overlap with the COVID-19 pandemic. Despite these hurdles, the MoHFW, along with strong collaboration from development partners and stakeholders, successfully navigated the complex rollout. Future studies on the role of PCVs in reducing antibiotic resistance and the economic benefits of PCV introduction could help policymakers sustain funding and prioritize vaccine procurement decisions. Full article

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36 pages, 3120 KiB

Open AccessReview

Viral Infections in Elderly Individuals: A Comprehensive Overview of SARS-CoV-2 and Influenza Susceptibility, Pathogenesis, and Clinical Treatment Strategies

by Yanhao Huang, Shumin Li, Wenjie Ye, Haoyun Wang, Jun Su, Lijuan Gao, Ruohu Shi, Xinyi Mou, Sean Xiao Leng, Chanchan Xiao and Guobing Chen

Vaccines 2025, 13(4), 431; https://doi.org/10.3390/vaccines13040431 - 21 Apr 2025

Abstract

As age increases, the immune function of elderly individuals gradually decreases, increasing their susceptibility to infectious diseases. Therefore, further research on common viral infections in the elderly population, especially severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses, is crucial for scientific [...] Read more.

As age increases, the immune function of elderly individuals gradually decreases, increasing their susceptibility to infectious diseases. Therefore, further research on common viral infections in the elderly population, especially severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses, is crucial for scientific progress. This review delves into the genetic structure, infection mechanisms, and impact of coinfections with these two viruses and provides a detailed analysis of the reasons for the increased susceptibility of elderly individuals to dual viral infections. We evaluated the clinical manifestations in elderly individuals following coinfections, including complications in the respiratory, gastrointestinal, nervous, and cardiovascular systems. Ultimately, we have summarized the current strategies for the prevention, diagnosis, and treatment of SARS-CoV-2 and influenza coinfections in older adults. Through these studies, we aim to reduce the risk of dual infections in elderly individuals and provide a scientific basis for the prevention, diagnosis, and treatment of age-related viral diseases, thereby improving their health status. Full article

(This article belongs to the Special Issue A One-Health Perspective on Immunization Against Infectious Diseases)

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11 pages, 632 KiB

Open AccessArticle

Intranasal Sendai Virus Vaccination of Seropositive Children 1 to 2 Years of Age in a Phase I Clinical Trial Boosts Immune Responses Toward Human Parainfluenza Virus Type 1

by Elisabeth Adderson, Kim J. Allison, Kristen Branum, Robert E. Sealy, Bart G. Jones, Sherri L. Surman, Rhiannon R. Penkert, Randall T. Hayden, Charles J. Russell, Allen Portner, Karen S. Slobod and Julia L. Hurwitz

Vaccines 2025, 13(4), 430; https://doi.org/10.3390/vaccines13040430 - 19 Apr 2025

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Abstract

Background/Objectives: Human parainfluenza virus type 1 (hPIV-1) is a major cause of serious respiratory diseases in young children. Annually, hPIV-1 results in approximately 10,000 hospitalizations in the United States due to croup, bronchiolitis, and/or pneumonia, and 10,000 deaths worldwide due to acute lower [...] Read more.

Background/Objectives: Human parainfluenza virus type 1 (hPIV-1) is a major cause of serious respiratory diseases in young children. Annually, hPIV-1 results in approximately 10,000 hospitalizations in the United States due to croup, bronchiolitis, and/or pneumonia, and 10,000 deaths worldwide due to acute lower respiratory tract infections among children less than 5 years of age. Despite the burden of disease, no vaccine for hPIV-1 is currently approved. Sendai virus (SeV) is a murine PIV-1. It has structural similarities with hPIV-1 and is currently under clinical development as an hPIV-1 Jennerian vaccine. Attributes of SeV include the following: (a) needleless delivery, (b) rapid and durable serum antibody responses after a single intranasal administration, (c) durable IgG and IgA responses in the nasal mucosa, and (d) use as a platform for recombinant vaccines against multiple pediatric pathogens. Evaluation of the tolerability, safety, and immunogenicity of intranasal SeV in healthy adults and seropositive children 3 to 6 years of age was previously conducted and supported vaccine advancement to evaluation in younger children. Methods: Three seropositive children 1 to 2 years of age received a single intranasal dose of 5 × 10⁵ EID₅₀ SeV (SENDAI, Clinicaltrials.gov NCT00186927). Adverse events were collected for 28 days post-vaccine administration using diary cards and participants were followed for six months in total. Sera were collected longitudinally for clinical laboratory and virus-specific antibody tests. Nasal swabs were collected longitudinally for virus and mucosal antibody tests. Results: Intranasal SeV was well tolerated, with only mild grade 1–2 events that resolved spontaneously. No serious adverse events, medically attended adverse events, or adverse events causing protocol termination were reported. One participant had positive nasal swabs for inoculated SeV during the first week after vaccination. Although children had measurable PIV-1-specific serum antibodies at baseline, intranasal SeV vaccination resulted in significant serum antibody increases in all participants. Similarly, there were significant increases in PIV-1-specific nasal IgG and IgA levels in all participants. Elevated antibody levels persisted through the six months of follow-up. Conclusions: Intranasal SeV was well tolerated and uniformly immunogenic in seropositive children 1 to 2 years of age. Results encourage the further evaluation of SeV and SeV-based recombinants as potential intranasal vaccines for the prevention of infection by hPIV-1 and other serious respiratory pathogens. Full article

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

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14 pages, 559 KiB

Open AccessReview

Intratumoral Immunotherapy in Breast Cancer

by Camille C. Baumrucker, Nicole Harris, Susan Hoover and Brian J. Czerniecki

Vaccines 2025, 13(4), 429; https://doi.org/10.3390/vaccines13040429 - 19 Apr 2025

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Abstract

Breast cancer remains the most frequently diagnosed cancer and the second highest cause of cancer death in females. Metastatic recurrence that is resistant to traditional therapies presents a major challenge, necessitating the development of an innovative treatment strategy. Immunotherapy has gained popularity in [...] Read more.

Breast cancer remains the most frequently diagnosed cancer and the second highest cause of cancer death in females. Metastatic recurrence that is resistant to traditional therapies presents a major challenge, necessitating the development of an innovative treatment strategy. Immunotherapy has gained popularity in the treatment of cancer, particularly melanoma, lung cancer, and more recently breast cancer. Major developments in immunotherapy have been made with a better understanding of the tumor microenvironment and how the microenvironment can be manipulated to induce an anti-tumor immune response. Intratumorally delivered immunotherapy can be used to create a local immune response. This review provides a comprehensive overview of intratumoral immunotherapy for breast cancer and its resultant changes in the tumor microenvironment. The discussed immunotherapeutics include oncolytic viruses, nucleic acids, innate immune agonists, bacteria, chimeric antigen receptor T cells, and dendritic cells. The review also evaluates completed clinical trials using these therapies. Lastly, the review offers future perspectives in the development of breast cancer immunotherapy. Full article

(This article belongs to the Section Cancer Vaccines and Immunotherapy)

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20 pages, 2047 KiB

Open AccessArticle

Design and Preliminary Immunogenicity Evaluation of Nipah Virus Glycoprotein G Epitope-Based Peptide Vaccine in Mice

by Seungyeon Kim, Rochelle A. Flores, Seo Young Moon, Seung Yun Lee, Bujinlkham Altanzul, Jiwon Baek, Eun Bee Choi, Heeji Lim, Eun Young Jang, Yoo-kyoung Lee, In-Ohk Ouh and Woo H. Kim

Vaccines 2025, 13(4), 428; https://doi.org/10.3390/vaccines13040428 - 18 Apr 2025

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Abstract

Background: The emergence of several paramyxoviruses, including Nipah virus (NiV), makes continued efforts in vaccine development as part of pandemic preparedness efforts necessary. Although NiV is a zoonotic pathogen with high case fatality, there is still no licensed vaccine. Methods: Herein, NiV attachment [...] Read more.

Background: The emergence of several paramyxoviruses, including Nipah virus (NiV), makes continued efforts in vaccine development as part of pandemic preparedness efforts necessary. Although NiV is a zoonotic pathogen with high case fatality, there is still no licensed vaccine. Methods: Herein, NiV attachment glycoprotein G (NiV-G), which is crucial to host cell receptor binding, was used to develop Nipah epitope-based peptide vaccines. A total of 39 B- and T-cell epitopes of NiV-G were shortlisted for peptide synthesis and evaluation using in silico analysis. Results: The in vitro antigenicity evaluation of the peptide candidates showed eight synthesized peptides (G7, stalk-domain epitopes) with relatively high binding to NiV-G antibody-positive serum (A_450nm: 1.39–3.78). Moreover, nine-mer (9-mer) peptides were found to be less reactive than their longer peptide counterparts (15–30 aa, G7-1, and G7-4), but 9-mer activity was enhanced with cyclization (NPLPFREYK, A_450nm: 2.66) and C-terminal amidation modification (NPLPFREYK-NH2, A_450nm: 1.39). Subsequently, in vivo validation in immunized mice revealed the immunogenicity potential of the G7-1 peptide vaccine (30 aa, NENVNEKCKFTLPPLKIHECNISCPNPLPF) to elicit a strong antigen-specific antibody response against their homologous peptide antigen (I.V., A_450nm: 1.48 ± 0.78; I.M., A_450nm: 1.66 ± 0.66). However, antibody binding to recombinant NiV-G protein remained low, suggesting limited recognition to the native antigen. Conclusions: This study focused on the preliminary screening and validation of peptide vaccines using single formulations with minimal modifications in the peptide candidates. Our findings collectively show the immunogenic potential of the NiV-G stalk-based epitope peptide vaccine as a novel therapeutic for NiV and underscores the need for strategic design, delivery, and formulation optimization to enhance its protective efficacy and translational application. Full article

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

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10 pages, 4148 KiB

Open AccessArticle

Characterization of Cellular and Humoral Immunity to Commercial Cattle BVDV Vaccines in White-Tailed Deer

by Paola M. Boggiatto, Mitchell V. Palmer, Steven C. Olsen and Shollie M. Falkenberg

Vaccines 2025, 13(4), 427; https://doi.org/10.3390/vaccines13040427 - 18 Apr 2025

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Abstract

Background/Objectives: White-tailed deer (Odocoileus virginianus) (WTD) play a central role at the human–livestock–wildlife interface, given their contribution to the spread of diseases that can affect livestock. These include a variety of bacterial, viral, and prion diseases with significant economic impact. Given [...] Read more.

Background/Objectives: White-tailed deer (Odocoileus virginianus) (WTD) play a central role at the human–livestock–wildlife interface, given their contribution to the spread of diseases that can affect livestock. These include a variety of bacterial, viral, and prion diseases with significant economic impact. Given the implications for WTD as potential reservoirs for a variety of diseases, methods for prevention and disease control in WTD are an important consideration. Methods: Using commercial livestock vaccines against bovine viral diarrhea virus (BVDV) in killed and modified live formulations, we test the ability of WTD to develop humoral and cellular immune responses following vaccination. Results: We demonstrate that, similar to cattle, WTD develop humoral immune responses to both killed and modified live formulations. Conclusions: As the farmed deer industry and the use of livestock vaccines in non-approved species grow, this type of information will help inform and develop improved husbandry and veterinary care practices. Additionally, while we were unable to detect cell-mediated immune responses to the vaccine, we established PrimeFlow as a method to detect IFN-γ responses in specific T cell populations, adding another level of resolution to our ability to understand WTD immune responses. Full article

(This article belongs to the Special Issue Viral Infections, Host Immunity and Vaccines)

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13 pages, 253 KiB

Open AccessArticle

Evaluating HPV Vaccination Behavior and Willingness to Be Vaccinated and Associated Factors Among University Students in Italy

by Francesca Licata, Concetta Arianna Scicchitano, Maria Rita Caracciolo and Aida Bianco

Vaccines 2025, 13(4), 426; https://doi.org/10.3390/vaccines13040426 - 18 Apr 2025

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Abstract

Objectives: The aim of the present study was to provide insight into potential predictors of HPV vaccination uptake and the willingness to get vaccinated. Methods: This cross-sectional study was conducted among university students using an online, anonymous, self-administered questionnaire. Vaccine hesitancy was measured [...] Read more.

Objectives: The aim of the present study was to provide insight into potential predictors of HPV vaccination uptake and the willingness to get vaccinated. Methods: This cross-sectional study was conducted among university students using an online, anonymous, self-administered questionnaire. Vaccine hesitancy was measured according to the adult Vaccine Hesitancy Scale (aVHS). Sociodemographic characteristics, beliefs about vaccination decision-making, vaccination behavior, and willingness to receive the HPV vaccine among unvaccinated students, and sources of information about vaccinations were investigated. Results: Among the 542 sampled students, 11.1% were classified as vaccine-hesitant. About one third (31.7%) had not received the HPV vaccination. Males, older students, those who had not received the dTap-IPV booster dose, and those being discouraged from getting vaccinated by a healthcare worker were more likely not to be vaccinated. Students having one parent holding a university degree or higher were more likely to be vaccinated compared to those having parents with a high school diploma or less. Among unvaccinated students, 65.7% were willing to get vaccinated against HPV, and it was positively associated with a low aVHS score and female gender, as well as being enrolled in medical and life sciences majors. Conclusions: Suboptimal HPV vaccination uptake was observed, especially among male and older university students. Insights from the present study highlight the need to address misconceptions about HPV infection and vaccines by providing facts that can be used in conversations with individuals who may feel insecure after having heard various myths about HPV vaccination. Full article

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

16 pages, 3254 KiB

Open AccessArticle

Low Antibody-Dependent Enhancement of Viral Entry Activity Supports the Safety of Inactivated SARS-CoV-2 Vaccines

by Xiaofang Peng, Yuru Han, Song Xue, Yunjiao Zhou, Weiyu Jiang, Anqi Xia, Wei Wu, Yidan Gao, Fan Wu and Qiao Wang

Vaccines 2025, 13(4), 425; https://doi.org/10.3390/vaccines13040425 - 18 Apr 2025

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Abstract

Background/Objectives: The antibody-dependent enhancement (ADE) of viral entry has been documented for SARS-CoV-2 infection both in vitro and in vivo. However, the potential for the SARS-CoV-2 vaccination to elicit similar ADE effects remains unclear. Methods: In this study, we assessed the in vitro [...] Read more.

Background/Objectives: The antibody-dependent enhancement (ADE) of viral entry has been documented for SARS-CoV-2 infection both in vitro and in vivo. However, the potential for the SARS-CoV-2 vaccination to elicit similar ADE effects remains unclear. Methods: In this study, we assessed the in vitro ADE potential of monoclonal antibodies (mAbs) derived from individuals vaccinated with the inactivated SARS-CoV-2 vaccine and compared them to those from one convalescent donor. Results: Our analysis revealed no significant difference in binding affinity or neutralizing capacity between the vaccinated and convalescent mAbs. However, the inactivated SARS-CoV-2 vaccination induced fewer ADE-inducing mAbs, particularly those targeting the Class III epitope on the receptor-binding domain (RBD) compared to those from the convalescent individual. Moreover, no significant in vitro ADE was detected in either vaccinated or convalescent sera, indicating low levels of ADE-inducing antibodies in the sera. Conclusions: An inactivated SARS-CoV-2 vaccination induces fewer ADE-inducing antibodies compared to natural infection, further emphasizing the safety of inactivated SARS-CoV-2 vaccines. Full article

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

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50 pages, 3587 KiB

Open AccessReview

Beyond the Pandemic Era: Recent Advances and Efficacy of SARS-CoV-2 Vaccines Against Emerging Variants of Concern

by Ankita Saha, Sounak Ghosh Roy, Richa Dwivedi, Prajna Tripathi, Kamal Kumar, Shashank Manohar Nambiar and Rajiv Pathak

Vaccines 2025, 13(4), 424; https://doi.org/10.3390/vaccines13040424 - 17 Apr 2025

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Abstract

Vaccination has been instrumental in curbing the transmission of SARS-CoV-2 and mitigating the severity of clinical manifestations associated with COVID-19. Numerous COVID-19 vaccines have been developed to this effect, including BioNTech-Pfizer and Moderna’s mRNA vaccines, as well as adenovirus vector-based vaccines such as [...] Read more.

Vaccination has been instrumental in curbing the transmission of SARS-CoV-2 and mitigating the severity of clinical manifestations associated with COVID-19. Numerous COVID-19 vaccines have been developed to this effect, including BioNTech-Pfizer and Moderna’s mRNA vaccines, as well as adenovirus vector-based vaccines such as Oxford–AstraZeneca. However, the emergence of new variants and subvariants of SARS-CoV-2, characterized by enhanced transmissibility and immune evasion, poses significant challenges to the efficacy of current vaccination strategies. In this review, we aim to comprehensively outline the landscape of emerging SARS-CoV-2 variants of concern (VOCs) and sub-lineages that have recently surfaced in the post-pandemic years. We assess the effectiveness of existing vaccines, including their booster doses, against these emerging variants and subvariants, such as BA.2-derived sub-lineages, XBB sub-lineages, and BA.2.86 (Pirola). Furthermore, we discuss the latest advancements in vaccine technology, including multivalent and pan-coronavirus approaches, along with the development of several next-generation coronavirus vaccines, such as exosome-based, virus-like particle (VLP), mucosal, and nanomaterial-based vaccines. Finally, we highlight the key challenges and critical areas for future research to address the evolving threat of SARS-CoV-2 subvariants and to develop strategies for combating the emergence of new viral threats, thereby improving preparedness for future pandemics. Full article

(This article belongs to the Special Issue SARS-CoV-2 Variants, Vaccines, and Immune Responses)

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17 pages, 2557 KiB

Open AccessSystematic Review

Comparative Efficacy of Immune Checkpoint Inhibitors and Therapeutic Vaccines in Solid Tumors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

by Rasha Babiker, Adil Farooq Wali, Mohamed El-Tanani, Syed Arman Rabbani, Imran Rangraze, Shakta Mani Satyam, Mohamed Anas Patni and Yahia El-Tanani

Vaccines 2025, 13(4), 423; https://doi.org/10.3390/vaccines13040423 - 17 Apr 2025

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Abstract

Background: Immune checkpoint inhibitors (ICIs) and therapeutic vaccines have emerged as promising immunotherapeutic strategies for solid tumors. However, their comparative efficacy in improving overall survival (OS) remains unclear. This systematic review and meta-analysis aimed to evaluate the efficacy of ICIs and therapeutic [...] Read more.

Background: Immune checkpoint inhibitors (ICIs) and therapeutic vaccines have emerged as promising immunotherapeutic strategies for solid tumors. However, their comparative efficacy in improving overall survival (OS) remains unclear. This systematic review and meta-analysis aimed to evaluate the efficacy of ICIs and therapeutic vaccines in improving OS in patients with solid tumors. Methods: A comprehensive search was conducted across PubMed, Cochrane Library, Embase, and Clinical Trials.gov for randomized controlled trials (RCTs) published between 1 January 2010 and 31 December 2024. Studies comparing ICIs or therapeutic vaccines against control treatments (placebo, standard of care, or active comparators) in adults with solid tumors were included. The primary outcome was OS, and data were pooled using RevMan (web). Risk of bias was assessed using the Cochrane Risk of Bias tool. Results: Thirteen RCTs involving 10,991 participants were included. A total of 5722 of them were treated with therapeutic vaccines or checkpoint inhibitors. Therapeutic vaccines demonstrated insignificant improvement in OS, with a pooled mean difference of 1.89 months (95% CI: −0.54–4.31; P = 0.13), although with homogeneity (I² = 0%). ICIs showed a statistically significant OS benefit, with a pooled mean difference of 1.32 months (95% CI: 0.62–2.02; P = 0.0002) and low heterogeneity (I² = 12%). Conclusions: Therapeutic vaccines provide a larger but less consistent benefit, whereas ICIs offer modest but more consistent survival advantage. These findings support the need for personalized immunotherapy approaches as well as further research to identify predictive biomarkers and optimize treatment strategies by acquiring deep insights into the TME dynamic and behaviors. Full article

(This article belongs to the Special Issue Cancer Vaccines and Immunotherapy: Latest Advances, Limitations and Prospects)

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20 pages, 4272 KiB

Open AccessArticle

Adjuvant Templating Improves On-Target/Off-Target Antibody Ratio Better than Linker Addition for M2-Derived Peptide Amphiphile Micelle Vaccines

by Megan C. Schulte, Adam C. Boll, Natalie L. Conomos, Farnoushsadat Rezaei, Agustin T. Barcellona, Adam G. Schrum and Bret D. Ulery

Vaccines 2025, 13(4), 422; https://doi.org/10.3390/vaccines13040422 - 17 Apr 2025

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Abstract

Background: Peptide amphiphile micelles (PAMs) are a promising lipid-based nanotechnology currently in development for a variety of applications ranging from atherosclerosis to cancer therapy. Especially relevant for immune applications, PAMs improve trafficking through lymphatic vessels, enhance uptake by antigen-presenting cells, and inhibit the [...] Read more.

Background: Peptide amphiphile micelles (PAMs) are a promising lipid-based nanotechnology currently in development for a variety of applications ranging from atherosclerosis to cancer therapy. Especially relevant for immune applications, PAMs improve trafficking through lymphatic vessels, enhance uptake by antigen-presenting cells, and inhibit the protease-mediated degradation of cargo. However, the creation of the peptide amphiphiles (PAs) necessary to induce micellization often requires modifying an immunotarget peptide with non-native moieties, which can induce the production of off-target antibodies. Methods: PAs containing different linkers between the antigen and non-native flanking regions were synthesized and physically characterized. BALB/c mice were then subcutaneously immunized on days 0 and 14 with these formulations and ELISAs were conducted on the sera collected from vaccinated mice on day 35 to evaluate antibody responses. Results: We determined that Palm₂K-M2_2–16-(KE)₄ PAMs elicited off-target antibody responses and sought to avoid these unintended responses by adding linkers in between the M2_2–16 antigen and the non-native flanking regions (i.e., Palm₂K- and -(KE)₄) of the PA. Most significantly, the addition of diproline linkers on either side of the M2_2–16 antigen conferred a loss of β-sheet structure, whereas changing the method of lipid attachment from Palm₂K- to Pam₂CS-induced the formation of primarily spherical micelles compared to a mixture of spherical and short cylindrical micelles. Despite these morphological changes, all linker-containing PAMs still induced the production of off-target antibodies. Excitingly, however, the formulation containing a Pam₂CS moiety (intended to mimic the adjuvanticity of the TLR2 agonist adjuvant Pam₂CSK₄) elicited high on-target antibody titers similar to those induced by PAMs co-delivered with Pam₂CSK₄. Conclusions: While the linkers tested did not completely eliminate the production of off-target antibodies elicited by the PAMs, the inclusion of a Pam₂CS moiety both increased the amount of on-target antibodies and improved the ratio of on-target to off-target antibodies in response to the M2_2–16 vaccine. Full article

(This article belongs to the Special Issue Synthetic Vaccines)

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16 pages, 2487 KiB

Open AccessArticle

Oral Delivery of Lactococcus lactis Expressing Full-Length S Protein via Alginate–Chitosan Capsules Induces Immune Protection Against PEDV Infection in Mice

by Miaoyan Yang, Denglong Xie, Wei Ji, Shu Jeffrey Zhu and Yongqi Zhou

Vaccines 2025, 13(4), 421; https://doi.org/10.3390/vaccines13040421 - 17 Apr 2025

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Abstract

Background/Objectives: Porcine epidemic diarrhea (PED) is a highly contagious enteric infectious disease that causes severe morbidity and mortality in piglets, posing significant economic losses to the swine industry worldwide. Oral vaccines based on Lactococcus lactis offer a promising approach due to their [...] Read more.

Background/Objectives: Porcine epidemic diarrhea (PED) is a highly contagious enteric infectious disease that causes severe morbidity and mortality in piglets, posing significant economic losses to the swine industry worldwide. Oral vaccines based on Lactococcus lactis offer a promising approach due to their safety and genetic manipulability. This study aims to develop and evaluate an oral L. lactis-based vaccine expressing the full-length PEDV S protein. Methods: A recombinant L. lactis strain expressing the PEDV S protein was constructed and encapsulated in alginate–chitosan microcapsules. Vaccine stability was tested in simulated digestive fluids, and mice were orally immunized. Immune responses were evaluated by measuring specific antibodies, cytokines, and lymphocyte proliferation. Results: The recombinant L. lactis NZ3900/pNZ8149-S strain successfully expressed the full-length PEDV S protein and maintained stable plasmid inheritance. Oral immunization in mice induced detectable PEDV-specific immune responses. Both encapsulated and non-encapsulated vaccines stimulated the production of IgG and sIgA antibodies, as well as cytokines associated with Th1 and Th2 responses. Notably, encapsulation with alginate–chitosan significantly enhanced bacterial survival in digestive conditions and further amplified immune responses, including higher antibody titers, elevated levels of IFN-γ, IL-4, and IL-10, and greater lymphocyte proliferation, indicating improved immune memory. Conclusions: The oral L. lactis NZ3900/pNZ8149-S vaccine expressing the PEDV S protein effectively induced systemic and mucosal immunity in mice. Encapsulation with alginate–chitosan further enhanced its immunogenicity and stability in gastrointestinal conditions. These results suggest that both the engineered L. lactis strain and the encapsulation strategy contribute to the development of a promising oral vaccine platform for controlling PEDV in swine populations. Full article

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22 pages, 1487 KiB

Open AccessReview

Monitoring Immune Responses to Vaccination: A Focus on Single-Cell Analysis and Associated Challenges

by LaToya Montgomery and Anis Larbi

Vaccines 2025, 13(4), 420; https://doi.org/10.3390/vaccines13040420 - 16 Apr 2025

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Abstract

Monitoring the immune response to vaccination encompasses both significant challenges and promising opportunities for scientific advancement. The primary challenge lies in the inherent complexity and interindividual variability of immune responses, influenced by factors including age, genetic background, and prior immunological history. This variability [...] Read more.

Monitoring the immune response to vaccination encompasses both significant challenges and promising opportunities for scientific advancement. The primary challenge lies in the inherent complexity and interindividual variability of immune responses, influenced by factors including age, genetic background, and prior immunological history. This variability necessitates the development of sophisticated, highly sensitive assays capable of accurately quantifying immune parameters such as antibody titers, T-cell responses, and cytokine profiles. Furthermore, the temporal dynamics of the immune response require comprehensive longitudinal studies to elucidate the durability and quality of vaccine-induced immunity. Challenges of this magnitude pave the way for immunological research advancements and diagnostic methodologies. Cutting-edge monitoring techniques, such as high-throughput sequencing and advanced flow cytometry, enable deeper insights into the mechanistic underpinnings of vaccine efficacy and contribute to the iterative design of more effective vaccines. Additionally, the integration of analytical tools holds the potential to predict immune responses and tailor personalized vaccination strategies. This will be addressed in this review to provide insight for enhancing public health outcomes and fortifying preparedness against future infectious disease threats. Full article

(This article belongs to the Special Issue Analysis of Vaccine-Induced Adaptive Immune Responses)

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13 pages, 877 KiB

Open AccessArticle

Therapeutic Vaccinations with p210 Peptides in Imatinib-Treated Chronic Myeloid Leukemia Patients: 10 Years Follow-Up of GIMEMA CML0206 and SI0207 Studies

by Anna Sicuranza, Massimo Breccia, Francesco Iuliano, Gabriele Gugliotta, Fausto Castagnetti, Monia Lunghi, Andrea Patriarca, Tamara Intermesoli, Luigiana Luciano, Antonella Russo Rossi, Giovanna Rege Cambrin, Vladan Vucinic, Michele Malagola, Alessandra Malato, Elisabetta Abruzzese, Mariella D’Adda, Sara Galimberti, Marzia Defina, Vincenzo Sammartano, Cristiana Cafarelli, Emanuele Cencini, Alessandra Cartocci, Paola Pacelli, Alfonso Piciocchi, Arianna Rughini, Dietger Niederwieser and Monica Bocchia Show full author list Hide full author list

Vaccines 2025, 13(4), 419; https://doi.org/10.3390/vaccines13040419 - 16 Apr 2025

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Abstract

Background: We previously showed that peptides encompassing the unique b3a2 or b2a2 breakpoint amino-acid sequence of oncogenic p210 induced peptide-specific T-cell responses in chronic myeloid leukemia (CML) patients. Methods: From 2007 to 2011, two multicenter peptide vaccine phase II studies, GIMEMA CML0206 [...] Read more.

Background: We previously showed that peptides encompassing the unique b3a2 or b2a2 breakpoint amino-acid sequence of oncogenic p210 induced peptide-specific T-cell responses in chronic myeloid leukemia (CML) patients. Methods: From 2007 to 2011, two multicenter peptide vaccine phase II studies, GIMEMA CML0206 and SI0207, enrolling overall 109 CML patients (68 b3a2 and 41 b2a2) with persistence of molecular disease during imatinib treatment, were carried out. Peptide vaccination schedule included the following: “immunization phase” (six vaccinations every 2 weeks); “reinforcement” phase (three monthly boosts) and “maintenance” phase (two boosts at 3-month intervals). GM-CSF (granulocyte-macrophage-colony-stimulating factor, sarmograstim) served as the immunological adjuvant. Results: The short-term results (at completion of vaccine protocol—12 months) and long-term follow-up are reported. All patients completed the vaccination schedule with no toxicity. After vaccinations, the BCR::ABL1 peptide-specific CD4+ T-cell response was documented in 80% of patients. In the short term, 30% of patients achieved a reduction in BCR::ABL1, while the majority showed stable molecular disease with fluctuations. The median follow-up since diagnosis and last vaccination are 18 and 10 years, respectively, with an overall survival (OS) rate at 18 years of 89%. In addition, 97/109 (89%) patients are alive, while 12/109 (11%) died of CML-unrelated reasons. Overall, 18/109 (16.5%) patients are in treatment-free remission (TFR) for a median time of 48 months. Conclusions: The long-term results of p210 peptide vaccinations in CML patients with persisting disease during imatinib treatment showed its feasibility, safety, absence of off-targets events, high OS and not negligible rate of successful TFR. Active immunotherapeutic approaches in CML patients with low disease burden, eventually employing newer vaccine strategies such as mRNA vaccines, may be reconsidered. Full article

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17 pages, 2282 KiB

Open AccessReview

Host–Pathogen Interaction Interface: Promising Candidate Targets for Vaccine-Induced Protective and Memory Immune Responses

by Gloria G. Guerrero, Vicente Madrid-Marina, Aurora Martínez-Romero, Kirvis Torres-Poveda and Juan Manuel Favela-Hernández

Vaccines 2025, 13(4), 418; https://doi.org/10.3390/vaccines13040418 - 16 Apr 2025

Viewed by 440

Abstract

Vaccine formulations are a successful strategy against pathogen transmission because vaccine candidates induce effective and long-lasting memory immune responses (B and CD4+ T cells) at systemic and mucosal sites. Extracellular vesicles of lipoproteins, bioactive compounds from plants and invertebrates (sponges) encapsulated in liposomes, [...] Read more.

Vaccine formulations are a successful strategy against pathogen transmission because vaccine candidates induce effective and long-lasting memory immune responses (B and CD4+ T cells) at systemic and mucosal sites. Extracellular vesicles of lipoproteins, bioactive compounds from plants and invertebrates (sponges) encapsulated in liposomes, and glycoproteins can target these sites. The vaccine candidates developed can mimic microbial pathogens in a way that successfully links the innate and adaptive immune responses. In addition, vaccines plus adjuvants promote and maintain an inflammatory response. In this review, we aimed to identify the host–pathogen interface as a rich source of candidate targets for vaccine-induced protective and long-lasting memory immune responses. Full article

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

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14 pages, 852 KiB

Open AccessArticle

Safety Analysis of Simultaneous Vaccination of Japanese Encephalitis Attenuated Live Vaccine and Measles, Mumps, and Rubella Combined Attenuated Live Vaccine from 2020 to 2023 in Guangzhou, China

by Jie Liu, Yong Huang, Fengrui Jing, Yan Kang, Qiaojuan Liu, Zhiwei Zheng, Chunhuan Zhang, Xiaofeng Liang and Zhoubin Zhang

Vaccines 2025, 13(4), 417; https://doi.org/10.3390/vaccines13040417 - 16 Apr 2025

Viewed by 190

Abstract

Objectives: Our objectives were to evaluate the safety of the simultaneous vaccination of Japanese encephalitis attenuated live vaccine (JEV-L) and measles, mumps, and rubella combined attenuated live vaccine (MMR) in children and to provide a reference for the implementation of the strategy of [...] Read more.

Objectives: Our objectives were to evaluate the safety of the simultaneous vaccination of Japanese encephalitis attenuated live vaccine (JEV-L) and measles, mumps, and rubella combined attenuated live vaccine (MMR) in children and to provide a reference for the implementation of the strategy of simultaneous vaccination with the two vaccines. Methods: The data of adverse events following immunization (AEFI) and vaccination for JEV-L and MMR from 2020 to 2023 were extracted through the Guangdong Province Vaccine Distribution and Vaccination Management Information System and the Chinese National AEFI Information System (CNAEFIS). The inclusion criteria were that children were born after 1 October 2019, and received the first dose of JEV-L or MMR after 1 June 2020, in accordance with the starting age for vaccination (8 months). The study used the number of vaccine doses as the denominator to calculate and compare the reporting rates of cases and calculated the relative risk (RR) of adverse reactions and the 95% confidence interval (CI). Results: In Guangzhou, a total of 214,238 doses of JEV-L were administered to children. JEV-L and MMR were co-administered in 464,009 doses, and MMR was administered separately in 241,150 doses. The overall reporting incidence rates of AEFI (per 100,000 doses) for JEV-L, the simultaneous vaccination group, and MMR were 11.20, 53.02, and 60.96, respectively. Among children aged 8 months in Guangzhou, 57.98% (463,512/799,423) received the simultaneous administration of JEV-L and MMR. In the reported AEFI events, general reactions accounted for 87.50% in the JEV-L group, 88.21% in the simultaneous vaccination group, and 89.80% in the MMR separate group. The incidence rates of common adverse reactions were 9.80, 46.7, and 54.74, respectively. The incidence rates of rare adverse reactions were 0.93, 3.88, and 2.90, respectively. The reporting incidence rates of fever ≥38.6 °C after vaccination were 4.20, 16.16, and 17.83 for the JEV-L separate group, simultaneous vaccination group, and MMR separate group, respectively. There was a significant difference between the simultaneous vaccination group and the JEV-L separate group (RR = 3.848, 95% CI = 1.927, 7.683), while no significant difference was found compared with the MMR separate group (RR = 0.906, 95% CI = 0.623, 1.318). The simultaneous vaccination group showed no significant differences in the reporting incidence rates of local redness and induration compared with the two separate vaccination groups (RR = 1.385, 95% CI = 0.144, 13.315; RR = 0.390, 95% CI = 0.087, 1.743; RR = 0.520, 95% CI = 0.033, 8.314). No significant differences were found in the incidence rates of rare adverse reactions such as maculopapular rash, urticaria, and thrombocytopenic purpura. Conclusions: The AEFI reporting incidence rate for the first dose of the simultaneous vaccination of JEV-L and MMR in 8-month-old children in Guangzhou is between the rates of the two separate groups. Compared with the MMR separate group, the simultaneous vaccination group does not increase the risk of adverse reactions. Full article

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16 pages, 3109 KiB

Open AccessArticle

Humanized Major Histocompatibility Complex Transgenic Mouse Model Can Play a Potent Role in SARS-CoV-2 Human Leukocyte Antigen-Restricted T Cell Epitope Screening

by Jiejie Zhang, Feimin Fang, Yue Zhang, Xuelian Han, Yuan Wang, Qi Yin, Keyu Sun, Haisheng Zhou, Hanxiong Qin, Dongmei Zhao, Wanbo Tai, Jun Zhang, Zhang Zhang, Tiantian Yang, Yuwei Wei, Shuai Zhang, Shuai Li, Min Li and Guangyu Zhao

Vaccines 2025, 13(4), 416; https://doi.org/10.3390/vaccines13040416 - 15 Apr 2025

Viewed by 152

Abstract

Background: COVID-19, caused by SARS-CoV-2, poses a significant threat to human health. Vaccines designed for T-cell epitopes play an important role in eliminating the virus. However, T cell epitope screening often requires the use of a large number of peripheral blood mononuclear cells [...] Read more.

Background: COVID-19, caused by SARS-CoV-2, poses a significant threat to human health. Vaccines designed for T-cell epitopes play an important role in eliminating the virus. However, T cell epitope screening often requires the use of a large number of peripheral blood mononuclear cells (PBMCs) from infected or convalescent patients, and if MHC humanized mice can be used for epitope screening, they will not have to wait for enough PBMCs to be available to screen for epitopes, thus buying time for epitope confirmation and vaccine design. Methods: In this study, we used SARS-CoV-2 BA.5 to infect HLA-A11/DR1, C57BL/6, hACE2 mice, and detected body weight changes, viral load, and pathological changes after infection. Fourteen days after the HLA-A11/DR1 and C57BL/6 mice were immunized against inactivated viruses, IgG antibodies were detected in mouse serum using ELISA, and IFN-γ produced by peptide stimulation of splenocytes was detected by ELISpot. Results: There is no obvious pathogenic phenotype of SARS-CoV-2 infection in HLA-A11/DR1 mice. Specific IgG antibodies were detected in serum after immunization of inactivated virus in both HLA-A11/DR1 and C57BL/6 mice, but specific IFN-γ was detected in splenocytes of HLA-A11/DR1 mice. Conclusions: Although HLA-A11/DR1 mice are unable to replicate the virus effectively in vivo, they are able to generate cellular immune responses after immunization inactivated viruses. Therefore, it can be used as a tool to substitute for human PBMCs in epitope screening, thus shortening the timeliness of T cell epitope screening and obtaining the immunogenicity information of new epitopes in a timely manner. Full article

(This article belongs to the Special Issue New Approaches to Vaccine Development and Delivery)

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16 pages, 643 KiB

Open AccessReview

Human Endogenous Retroviruses as Novel Therapeutic Targets in Neurodegenerative Disorders

by Elena Rita Simula, Seyedesomaye Jasemi, Davide Cossu, Milena Fais, Ilaria Cossu, Vanna Chessa, Mattia Canu and Leonardo Antonio Sechi

Vaccines 2025, 13(4), 415; https://doi.org/10.3390/vaccines13040415 - 15 Apr 2025

Viewed by 297

Abstract

Human Endogenous Retroviruses comprise approximately 8% of the human genome, serving as fragments of ancient retroviral infections. Although they are generally maintained in a silenced state by robust epigenetic mechanisms, specific HERV groups, particularly HERV-W and HERV-K, can become derepressed under specific pathological [...] Read more.

Human Endogenous Retroviruses comprise approximately 8% of the human genome, serving as fragments of ancient retroviral infections. Although they are generally maintained in a silenced state by robust epigenetic mechanisms, specific HERV groups, particularly HERV-W and HERV-K, can become derepressed under specific pathological conditions, thereby contributing to the initiation and progression of neuroinflammatory and neurodegenerative processes. Preclinical studies and clinical trials, such as those investigating monoclonal antibodies, indicate that directly targeting these elements may offer a novel therapeutic strategy. In this review, we provide an overview of HERVs′ biology, examine their role in neurodegenerative diseases such as amyotrophic lateral sclerosis, multiple sclerosis, Alzheimer′s disease, and Parkinson′s disease, and explore their therapeutic prospects, highlighting both the challenges and the potential future research directions needed to translate these approaches into clinical interventions. Full article

(This article belongs to the Special Issue Advances in Vaccines against Infectious Diseases)

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17 pages, 2493 KiB

Open AccessArticle

Adenosine 2B Receptor Signaling Impairs Vaccine-Mediated Protection Against Pneumococcal Infection in Young Hosts by Blunting Neutrophil Killing of Antibody-Opsonized Bacteria

by Shaunna R. Simmons, Alexsandra P. Lenhard, Michael C. Battaglia and Elsa N. Bou Ghanem

Vaccines 2025, 13(4), 414; https://doi.org/10.3390/vaccines13040414 - 15 Apr 2025

Viewed by 212

Abstract

Background/Objective: Neutrophils are essential for vaccine-mediated protection against pneumococcal infection and impairment in their antibacterial function contributes to reduced vaccine efficacy during aging. However, the signaling pathways that control the neutrophil responses in vaccinated hosts are not fully understood. The extracellular adenosine pathway [...] Read more.

Background/Objective: Neutrophils are essential for vaccine-mediated protection against pneumococcal infection and impairment in their antibacterial function contributes to reduced vaccine efficacy during aging. However, the signaling pathways that control the neutrophil responses in vaccinated hosts are not fully understood. The extracellular adenosine pathway is a known regulator of neutrophils in naïve hosts. The aim of this study was to test the role of this pathway in the function of neutrophils and their protection against infection upon vaccination as a function of the host’s age. Methods: To test the role of adenosine in the antimicrobial activity of neutrophils against antibody-opsonized pneumococci, we used bone marrow-derived neutrophils isolated from wild-type or specific-adenosine-receptors knock-out mice. To measure the effect of adenosine receptor signaling in vivo, we treated vaccinated mice with agonists or antagonists that were specific to the different adenosine receptors prior to pulmonary challenge with pneumococci and assessed the bacterial burden and clinical score post-infection. Results: We found that signaling via the adenosine 2B (A2BR) receptor but not the A2A or A1 receptors diminished the intracellular pneumococcal killing following antibody-mediated uptake in young hosts. In vivo, the agonism of the A2BR receptor significantly worsened the pneumococcal infection outcomes in young, vaccinated mice. In contrast, A2BR signaling had no effect on the intracellular bacterial killing by neutrophils from aged mice. Further, in vivo A2BR inhibition had no effect on the pneumococcal disease progression in aged, vaccinated mice. Conclusions: A2BR signaling reduced pneumococcal vaccine-mediated protection by impairing the antimicrobial activity of neutrophils against antibody-opsonized bacteria in young hosts. However, inhibiting this pathway was not sufficient to boost responses in aged hosts. Full article

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

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16 pages, 6590 KiB

Open AccessArticle

Vaccine Efficacy of a Replication-Competent Interferon-Expressing Porcine Reproductive and Respiratory Syndrome (PRRS) Virus Against NADC-34 Challenge

by Laura C. Miller, Sarah J. Anderson, Alexandra C. Buckley, Erin E. Schirtzinger, Mahamudul Hasan, Kaitlyn M. Sarlo Davila, Damarius S. Fleming, Kelly M. Lager, Jiuyi Li and Yongming Sang

Vaccines 2025, 13(4), 413; https://doi.org/10.3390/vaccines13040413 - 15 Apr 2025

Viewed by 248

Abstract

Background/Objectives: Porcine reproductive and respiratory syndrome virus (PRRSV) significantly impedes swine production due to rapid genetic variation and suppression of antiviral interferon (IFN) responses, leading to ineffective immunity. To address this, we developed IFNmix, a replication-competent PRRSV modified live vaccine (MLV) candidate [...] Read more.

Background/Objectives: Porcine reproductive and respiratory syndrome virus (PRRSV) significantly impedes swine production due to rapid genetic variation and suppression of antiviral interferon (IFN) responses, leading to ineffective immunity. To address this, we developed IFNmix, a replication-competent PRRSV modified live vaccine (MLV) candidate co-expressing three Type I IFN subclasses (IFNα, IFNβ, IFNδ) to enhance antiviral immunity. Methods: In two independent in vivo experiments, we compared the protection of IFNmix and a commercial PRRSV MLV vaccine during challenge with a virulent PRRSV strain. Clinical signs, antibody and cytokine production, viral replication, and lung pathology in IFNmix-vaccinated pigs were compared to those of commercial PRRSV vaccines and controls. Results: Pigs vaccinated with IFNmix exhibited similar anti-PRRSV antibody development, serum viral loads, lung lesions, and cytokine responses post-challenge with the virulent NADC34 strain, with comparable or lower body temperatures and weight gain, to pigs vaccinated with the commercial vaccines. While IFNmix showed early viral load reduction compared to the commercial vaccine (Days 7–14 post-challenge), it demonstrated similar efficacy in controlling PRRSV replication and lung pathology. Conclusions: These findings suggest that IFNmix, by expressing multiple IFNs, can potentially enhance innate and adaptive immune responses, offering a promising approach to improving PRRSV vaccine efficacy. Further studies are needed to evaluate IFNmix against a broader range of PRRSV strains and to optimize its attenuation and immunogenicity. Full article

(This article belongs to the Special Issue Immune Response After Respiratory Infection or Vaccination)

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16 pages, 4603 KiB

Open AccessArticle

M2e/NP Dual Epitope-Displaying Nanoparticles Enhance Cross-Protection of Recombinant HA Influenza Vaccine: A Universal Boosting Strategy

by Rui Liu, Lejun Yang, Jin Feng, Songchen Zhang, Liping Wu, Yingying Du, Dexin Kong, Yuhua Xu and Tao Peng

Vaccines 2025, 13(4), 412; https://doi.org/10.3390/vaccines13040412 - 15 Apr 2025

Viewed by 245

Abstract

Background/Objectives: Vaccination remains the most effective means of preventing influenza virus infections. However, the continuous antigenic drift and shift of influenza viruses lead to a reduced efficacy of the existing vaccines, necessitating vaccines capable of broad protection. Methods: To address this, [...] Read more.

Background/Objectives: Vaccination remains the most effective means of preventing influenza virus infections. However, the continuous antigenic drift and shift of influenza viruses lead to a reduced efficacy of the existing vaccines, necessitating vaccines capable of broad protection. Methods: To address this, we developed a modular vaccine strategy pairing a clinical-stage adjuvanted recombinant hemagglutinin (HA) vaccine (SCVC101) with OMN, a heptameric nanoparticle displaying conserved influenza A virus T-cell epitopes from nucleoprotein (NP) and matrix 2 ectodomain (M2e). Results: OMN induced cross-reactive M2e-specific antibodies, binding to diverse influenza A subtypes. Critically, the co-administration of OMN with SCVC101 enhanced cellular immunity and cross-protection without diminishing HA-induced humoral responses. Conclusions: This dual-antigen delivery system enables annual HA component updates, aligned with WHO recommendations, while the conserved OMN nanoparticle acts as a universal booster, leveraging existing production infrastructure. This approach offers a promising strategy for improving the influenza vaccine’s efficacy against emerging viral variants. Full article

(This article belongs to the Special Issue Recombinant Vaccine for Human and Animal Diseases)

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18 pages, 15954 KiB

Open AccessArticle

Multi-Antigen Viral-Vectored Vaccine Protects Against SARS-CoV-2 and Variants in a Lethal hACE2 Transgenic Mouse Model

by Shannon Stone, Amany Elsharkawy, J. D. Burleson, Mary Hauser, Arban Domi, Pratima Kumari, Zainab Nabi, Janhavi P. Natekar, Maciel Porto, Brian Backstedt, Mark Newman, Sreenivasa Rao Oruganti and Mukesh Kumar

Vaccines 2025, 13(4), 411; https://doi.org/10.3390/vaccines13040411 - 15 Apr 2025

Viewed by 395

Abstract

Widespread and rapidly evolving SARS-CoV-2 posed an unprecedented challenge to vaccine developers. GeoVax has designed a multiantigen SARS-CoV-2 vaccine, designated GEO-CM02 based on a Modified Vaccinia Virus (MVA) vector that expresses spike (S), membrane (M), and envelope (E) antigens. This experimental vaccine was [...] Read more.

Widespread and rapidly evolving SARS-CoV-2 posed an unprecedented challenge to vaccine developers. GeoVax has designed a multiantigen SARS-CoV-2 vaccine, designated GEO-CM02 based on a Modified Vaccinia Virus (MVA) vector that expresses spike (S), membrane (M), and envelope (E) antigens. This experimental vaccine was tested in the hACE2 transgenic mouse model to assess immunogenicity and efficacy. Administration of the vaccine in a two-dose regimen elicited high levels of neutralizing antibodies and provided complete protection, effectively reducing lung, olfactory bulb, and brain viral load and reducing lung inflammation following infection with original B.1 virus and the B.1.1.529 variant. In addition, GEO-CM02 conferred 80% protection against a lethal infection with the B.1.351 variant. GEO-CM02 vaccine efficacy studies also demonstrated a complete level of vaccine-induced protection with a single dose against the original B.1 virus and B.1.1.529 variant. GEO-CM02 effectively elicited functional T-cell responses in both prime and prime–boost groups. These data indicate that vaccination with the GEO-CM02 vaccine can induce immune responses that protect against severe disease induced by SARS-CoV-2 and its variants in a highly relevant pre-clinical model. Full article

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

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11 pages, 645 KiB

Open AccessArticle

Trends Towards Enhanced Rates and Sex Parity in HPV Vaccination in Croatia (2016–2023)

by Lucija Raic, Ivana Pavic Simetin, Emanuel Bradasevic, Antea Jezidzic, Tatjana Nemeth Blazic and Tamara Poljicanin

Vaccines 2025, 13(4), 410; https://doi.org/10.3390/vaccines13040410 - 15 Apr 2025

Viewed by 232

Abstract

Background/Objectives: Human papillomavirus (HPV) is a recognized cause of cervical cancer and is associated with several other malignancies, including those affecting the vagina, vulva, anus, penis, and head and neck. The introduction of the HPV vaccine has enabled the prevention of HPV-related cancers. [...] Read more.

Background/Objectives: Human papillomavirus (HPV) is a recognized cause of cervical cancer and is associated with several other malignancies, including those affecting the vagina, vulva, anus, penis, and head and neck. The introduction of the HPV vaccine has enabled the prevention of HPV-related cancers. This study aimed to determine the HPV vaccination coverage and examine trends in HPV vaccination in Croatia from 2016 to 2023 in the context of the national vaccination program. Methods: This retrospective study analyzed the aggregated school doctors’ data from 2016 to 2023. HPV vaccination coverages within the 2000–2008 birth cohorts were assessed based on the number of doses administrated, sex, and vaccination schedule, while for the trend analysis joinpoint regression was used. The vaccination coverage between sexes was tested using the chi-square test for trends and their ratio was calculated. Results: The HPV full-dose vaccination coverage increased significantly among the observed birth cohorts, from 4.49% in 2000 to 36.88% in 2008, with an APC = 33.97 and 95% CI: 29.37–42.43 (females from 7.74% to 44.98%, males from 1.44% to 29.14%). The highest recorded vaccination coverage was in the one-dose category (2008 female—52.78%). The vaccination coverage of females was significantly higher than that of males (the chi-square for the linear trend = 659.59, p < 0.001) and the female–male ratio decreased from 5.39 in 2000 to 1.54 in 2008. Conclusions: In Croatia, HPV vaccination coverage has increased since the introduction of the national HPV vaccination program. This positive trend was present in both sexes, and the rate ratio between female and male cohorts decreased. Full article

(This article belongs to the Special Issue Vaccination, Public Health and Epidemiology)

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15 pages, 1871 KiB

Open AccessArticle

Dynamics of SARS-CoV-2 IgG in Nursing Home Residents in Belgium Throughout Three BNT162b2 Vaccination Rounds: 19-Month Follow-Up

by Eline Meyers, Liselore De Rop, Claudia Gioveni, Fien Engels, Anja Coen, Tine De Burghgraeve, Marina Digregorio, Pauline Van Ngoc, Nele De Clercq, Laëtitia Buret, Samuel Coenen, Elizaveta Padalko, Els Duysburgh, Beatrice Scholtes, Jan Y. Verbakel, Stefan Heytens and Piet Cools

Vaccines 2025, 13(4), 409; https://doi.org/10.3390/vaccines13040409 - 15 Apr 2025

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Abstract

Background/Objectives: This study mapped antibody dynamics across three COVID-19 vaccination rounds (primary course, first, and second booster with BNT162b2) in Belgian nursing home residents (NHRs). Methods: Within a national SARS-CoV-2 serosurveillance study (February 2021–September 2022) across Belgian nursing homes, dried blood spots were [...] Read more.

Background/Objectives: This study mapped antibody dynamics across three COVID-19 vaccination rounds (primary course, first, and second booster with BNT162b2) in Belgian nursing home residents (NHRs). Methods: Within a national SARS-CoV-2 serosurveillance study (February 2021–September 2022) across Belgian nursing homes, dried blood spots were collected, on which anti-spike SARS-CoV-2 IgG antibodies were quantified by ELISA in international units/mL (IU/mL). Sociodemographic data were collected at the study start and infection history and vaccination data at each sampling round. Results: Infection-naïve NHRs had low antibody levels after primary course vaccination (geometric mean concentration (GMC) 292 IU/mL, 95% confidence interval (95% CI): 197–432), but increased tenfold after first booster (GMC 2168 IU/mL, 95% CI: 1554–3027). While antibodies among NHRs significantly declined within six months after primary vaccination (p < 0.0001), they remained stable for nine months post-booster (p > 0.05). Among primary vaccine non-responders, 92% (95% CI: 82–97%) developed antibodies after the first booster (GMC 594 IU/mL, 95% CI: 416–849), though tenfold lower than initial responders (GMC 4642 IU/mL, 95% CI: 3577–6022). Conclusions: These findings demonstrate that NHRs require tailored vaccination, prioritizing repeated immunization to improve serological outcomes in poor responders such as infection-naive NHRs. Regular immune monitoring could aid in implementing evidence-based vaccine strategies, ensuring optimal protection for vulnerable populations against SARS-CoV-2 and other infectious threats. Full article

(This article belongs to the Special Issue Population Immunity and Persistence to SARS-CoV-2 Induced by Infection and Vaccination, Protection Against New Infections and Implication for Further Vaccination: 2nd Edition)

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13 pages, 1030 KiB

Open AccessArticle

The Influence of the Associated Inactivated Vaccine Against Infectious Rhinotracheitis and Bovine Viral Diarrhea on the Formation and Duration of Colostral Immunity in Kazakh Whiteheaded Calves

by Yerbol Bulatov, Alina Kurmasheva, Zhanat Amanova, Ruslan Abitaev, Zhanna Sametova, Asselya Kyrgyzbayeva, Zhanat Kondybaeva, Sholpan Turyskeldi, Abdurakhman Ussembay, Dariya Toktyrova, Dana Mazbayeva, Yeraly Shayakhmetov, Aslan Kerimbayev, Damir Khussainov, Ma Wentao, Aralbek Rsaliyev and Yergali Abduraimov

Vaccines 2025, 13(4), 408; https://doi.org/10.3390/vaccines13040408 - 15 Apr 2025

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Abstract

Objectives: This article presents a study evaluating the antibody levels against infectious bovine rhinotracheitis (IBR) and bovine viral diarrhea (BVD) in Kazakh Whiteheaded calves born to dams immunized with an experimental inactivated combined vaccine against these infections. The vaccine formulation includes the [...] Read more.

Objectives: This article presents a study evaluating the antibody levels against infectious bovine rhinotracheitis (IBR) and bovine viral diarrhea (BVD) in Kazakh Whiteheaded calves born to dams immunized with an experimental inactivated combined vaccine against these infections. The vaccine formulation includes the strains “R-93” (IBR) and “Oregon C₂₄V” (BVD), which are preserved in the microorganism collection of the Research Institute for Biological Safety Problems. Methods: To assess the immune response in newborn calves, blood serum samples were collected before the first intake of colostrum, followed by weekly sampling for 28 weeks post-birth. The antibody response was determined using a virus neutralization assay on MDBK cell cultures and lamb testicle cell cultures. Results: The results demonstrated that the protective antibody level against the IBR virus (≥2 log₂) persisted for up to 25 weeks, while the protective level against the BVD virus (≥3 log₂) remained for 23 weeks. Based on these findings, the vaccine was deemed safe, as it did not induce abortions or clinical manifestations of the diseases. The overall duration of the colostral immunity in calves against the IBR and BVD viruses reached 23 weeks. Conclusions: Therefore, it is recommended that Kazakh Whiteheaded calves be vaccinated with the associated inactivated vaccine against infectious bovine rhinotracheitis and bovine viral diarrhea no earlier than 23 weeks of age. Full article

(This article belongs to the Special Issue Animal Diseases: Immune Response and Vaccines)

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13 pages, 1064 KiB

Open AccessArticle

Prevention of Cardiovascular Diseases with Standard-Dose Quadrivalent Influenza Vaccine in People Aged ≥50 Years in Australia During the 2017 A/H3N2 Epidemic

by Zubair Akhtar, Aye M. Moa, Timothy C. Tan, Ole Fröbert, Robert Menzies and C. Raina MacIntyre

Vaccines 2025, 13(4), 407; https://doi.org/10.3390/vaccines13040407 - 14 Apr 2025

Viewed by 236

Abstract

Background: In Australia, 2017 was a severe A/H3N2 season and, therefore, we estimated the effectiveness of standard-dose quadrivalent influenza vaccine in preventing hospitalization for cardiovascular disease (CVD) among New South Wales (NSW) residents aged ≥50 years. Methods: We conducted a nested, matched case–control [...] Read more.

Background: In Australia, 2017 was a severe A/H3N2 season and, therefore, we estimated the effectiveness of standard-dose quadrivalent influenza vaccine in preventing hospitalization for cardiovascular disease (CVD) among New South Wales (NSW) residents aged ≥50 years. Methods: We conducted a nested, matched case–control study within the 45 and Up study, linking data from the Australian Immunization Register, NSW Admitted Patient Data Collection and Pharmaceutical Benefits Schedule. Cases were individuals hospitalized for CVD and controls were those who were hospitalized for gastrointestinal diseases. The two groups were balanced using 1:1 propensity score matching based on age group (50–64, 65–74, 75–84, and ≥85 years) and sex. After adjusting for confounders (smoking, body mass index and income), we calculated the adjusted odds ratio (aOR) for vaccination during the season using multivariable logistic regression. E-values were estimated to assess residual confounding. Vaccine effectiveness (VE) was calculated as (1 − aOR) × 100. Results: There were 10,445 (4452 cases and 5993 controls) study participants. After matching, 8904 (85.2%) were retained with a mean age of 76.4 ± 10.4 years and 58.3% men. Following adjustment for confounders, the aOR of averting a CVD hospitalization was 0.15 (95% CI: 0.13 to 0.17; p < 0.001). The estimated VE against CVD hospitalization was 85% (95% CI: 83 to 87). We found an E-value of 12.82, indicating strong evidence of minimal residual confounding. Conclusions: In the severe 2017 influenza A/H3N2 season in Australia, we observed a high VE in preventing cardiovascular hospitalization despite a low VE against influenza infection prevention. Improving vaccine uptake may reduce cardiovascular burden. Full article

(This article belongs to the Special Issue Immunity to Influenza Viruses and Vaccines)

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28 pages, 5954 KiB

Open AccessReview

Next-Generation Adenoviral Vector-Based Vaccines for Severe Acute Respiratory Syndrome Coronavirus-2

by Muralimanohara S. T. Murala, Vivek Gairola, Ekramy E. Sayedahmed and Suresh K. Mittal

Vaccines 2025, 13(4), 406; https://doi.org/10.3390/vaccines13040406 - 14 Apr 2025

Viewed by 377

Abstract

This review systematically revises adenovirus (Ad) biology, vector structure, immune responses, and currently available Ad vector COVID-19 vaccines. It analyzes the challenges associated with the Ad vector-based vaccines, including preexisting vector immunity and other side effects. Moreover, this review explores novel and innovative [...] Read more.

This review systematically revises adenovirus (Ad) biology, vector structure, immune responses, and currently available Ad vector COVID-19 vaccines. It analyzes the challenges associated with the Ad vector-based vaccines, including preexisting vector immunity and other side effects. Moreover, this review explores novel and innovative strategies to overcome these constraints for developing next-generation vaccines for broad protection to cover emerging SARS-CoV-2 variants. The future refinement of Ad vaccine platforms will be pivotal in achieving durable immunity against emerging variants for global preparedness. Full article

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

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15 pages, 1187 KiB

Open AccessReview

Salmonella-Based Vaccine: A Promising Strategy for Type 1 Diabetes

by Mahmoud Singer, Fouad Kandeel and Mohamed I. Husseiny

Vaccines 2025, 13(4), 405; https://doi.org/10.3390/vaccines13040405 - 14 Apr 2025

Viewed by 609

Abstract

Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by the progressive destruction of insulin-producing β-cells in the pancreas. Currently, no therapy exists to halt or cure T1D. Vaccination with diabetic autoantigens may offer protection against T1D development. Genetically modified, attenuated Salmonella [...] Read more.

Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by the progressive destruction of insulin-producing β-cells in the pancreas. Currently, no therapy exists to halt or cure T1D. Vaccination with diabetic autoantigens may offer protection against T1D development. Genetically modified, attenuated Salmonella utilizing the Salmonella-Pathogenicity Island 2 (SPI2)-encoded Type Three Secretion System (T3SS) can elicit robust immune responses, making it an attractive vaccine platform. Using SPI2-T3SS to deliver an autoantigen alongside immunomodulators and anti-CD3 antibodies induces antigen-specific regulatory T-cells. Our preclinical studies demonstrated the efficacy of a Salmonella-based vaccine in both preventing and reversing autoimmune diabetes in non-obese diabetic (NOD) mice while also exploring its genetic modifications, underlying mechanisms, and delivery strategies. This review evaluates the advantages of an oral T1D vaccine employing live, attenuated Salmonella for autoantigen delivery. We also discuss future directions for advancing this strategy in the treatment of other autoimmune diseases. Full article

(This article belongs to the Special Issue Development of Novel Mucosal Vaccines: Advances in Technology and Delivery)

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18 pages, 1908 KiB

Open AccessArticle

Development of In Vitro Potency Methods to Replace In Vivo Tests for Enterovirus 71 Inactivated Vaccine (Human Diploid Cell-Based/Vero Cell-Based)

by Xuanxuan Zhang, Li Yi, Dan Yu, Jun Li, Xintian Li, Xing Wu, Fan Gao, Qian He, Wenhui Wang, Kaiwen Wang, Zejun Wang, Zhengling Liu, Yadong Li, Yong Zhao, Huiyi Li, Xiao Ma, Qingbing Zheng, Longfa Xu, Tong Cheng, Rui Zhu, Jing Guo, Jing Li, Qunying Mao and Zhenglun Liang Show full author list Hide full author list

Vaccines 2025, 13(4), 404; https://doi.org/10.3390/vaccines13040404 - 13 Apr 2025

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Abstract

Background: The three commercial Enterovirus 71 (EV71) inactivated vaccines which have effectively controlled the EV71 pandemic currently rely on inherent variable in vivo potency methods for batch release. To align with 3R (Replacement, Reduction, Refinement) principles and enhance quality control, this study referred [...] Read more.

Background: The three commercial Enterovirus 71 (EV71) inactivated vaccines which have effectively controlled the EV71 pandemic currently rely on inherent variable in vivo potency methods for batch release. To align with 3R (Replacement, Reduction, Refinement) principles and enhance quality control, this study referred to WHO guidelines and the European Pharmacopoeia to develop in vitro relative potency (IVRP) methods. Methods: Working standards tracing to phase 3 clinical vaccines were established. Manufacture-specific IVRP methods were developed and validated per ICH Q14/Q2(R2), utilizing conformational epitope-targeting neutralizing monoclonal antibodies (MAbs). One of the MAbs (CT11F9) recognition sites was clarified with Cryo-EM. Subsequently, the performance of IVRP was assessed using varied concentrations and heat-treated vaccines. The correlation between IVRP and in vivo methods was analyzed, followed by setting IVRP specifications. Results: The manufacturer-specific working standard exhibited ED50 values comparable to those of related phase 3 clinical vaccines. All IVRP methods achieved a relative bias/precision/total error ≤ 15%. The IVRP methods correlated with in vivo methods (p < 0.05, r > 0.9) can discriminate EV71 antigen concentrations (p < 0.01, r > 0.99) and indicate the stability of the vaccines. Cryo-EM was adopted to identify the epitopes recognized by CT11F9, revealing that this neutralizing antibody recognizes a conformational epitope spanning VP1-3 of the same protomer. Using 31–47 batches of commercial vaccines, IVRP specifications were proposed as 0.56–1.35, 0.58–1.40, and 0.54–1.50. Conclusions: Based on conformational epitope-targeting neutralizing MAbs, manufacturer-specific IVRP methods, which were sensitive to process variations and correlated with in vivo results, have been established. IVRP methods provide a reliable, animal-free alternative for EV71 vaccine batch release. Full article

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16 pages, 648 KiB

Open AccessReview

Vaccination and Platelet Biology: Unraveling the Immuno-Hemostatic Interplay

by Sneha Ratnapriya and Shivraj M. Yabaji

Vaccines 2025, 13(4), 403; https://doi.org/10.3390/vaccines13040403 - 13 Apr 2025

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Abstract

Platelets, which have been traditionally associated with hemostasis and thrombosis functions, now receive attention for their role in immune responses that may affect vaccine development and effectiveness. Through their interactions with immune cells and modulation of inflammation alongside their role in antigen presentation, [...] Read more.

Platelets, which have been traditionally associated with hemostasis and thrombosis functions, now receive attention for their role in immune responses that may affect vaccine development and effectiveness. Through their interactions with immune cells and modulation of inflammation alongside their role in antigen presentation, platelets become integral components of both innate and adaptive immune systems. New research shows platelets can improve vaccine effectiveness while reducing adverse side effects. During vaccine administration, platelets release cytokines and chemokines, which attract and stimulate immune cells to the injection site. Platelets work together with dendritic cells and T cells to support antigen processing and presentation, which leads to strong immune activation. Platelets’ pro-inflammatory mediators strengthen local immune responses to boost protective immunity generation. Significant attention has been given to platelet involvement in vaccine-related thrombotic events, including vaccine-induced immune thrombotic thrombocytopenia (VITT). The rarity and severity of these events demonstrate the need to investigate the complex interplay between vaccine mechanisms and platelet activation. Exploration of the platelet-immune axis can lead to new methods for improving both the effectiveness and safety of vaccines. Researchers are working on creating innovative approaches for treatments that target platelet receptors and thrombosis pathways without interfering with the regular hemostatic functions of platelets. New vaccine development methods and personalized immunization strategies can emerge from targeting platelets with adjuvants and immune modulators. Full article

(This article belongs to the Special Issue Immunotherapeutics for Treating Infectious Diseases and Beyond)

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Vaccines, Volume 13, Issue 4 (April 2025) – 98 articles

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