Vaccines

25 pages, 1446 KB

Open AccessEditor’s ChoiceReview

Exploring CD169⁺ Macrophages as Key Targets for Vaccination and Therapeutic Interventions

by Rianne G. Bouma, Aru Z. Wang and Joke M. M. den Haan

Vaccines 2025, 13(3), 330; https://doi.org/10.3390/vaccines13030330 - 20 Mar 2025

Cited by 4 | Viewed by 4832

CD169 is a sialic acid-binding immunoglobulin-like lectin (Siglec-1, sialoadhesin) that is expressed by subsets of tissue-resident macrophages and circulating monocytes. This receptor interacts with α2,3-linked Neu5Ac on glycoproteins as well as glycolipids present on the surface of immune cells and pathogens. CD169-expressing macrophages [...] Read more.

CD169 is a sialic acid-binding immunoglobulin-like lectin (Siglec-1, sialoadhesin) that is expressed by subsets of tissue-resident macrophages and circulating monocytes. This receptor interacts with α2,3-linked Neu5Ac on glycoproteins as well as glycolipids present on the surface of immune cells and pathogens. CD169-expressing macrophages exert tissue-specific homeostatic functions, but they also have opposing effects on the immune response. CD169⁺ macrophages act as a pathogen filter, protect against infectious diseases, and enhance adaptive immunity, but at the same time pathogens also exploit them to enable further dissemination. In cancer, CD169⁺ macrophages in tumor-draining lymph nodes are correlated with better clinical outcomes. In inflammatory diseases, CD169 expression is upregulated on monocytes and on monocyte-derived macrophages and this correlates with the disease state. Given their role in promoting adaptive immunity, CD169⁺ macrophages are currently investigated as targets for vaccination strategies against cancer. In this review, we describe the studies investigating the importance of CD169 and CD169⁺ macrophages in several disease settings and the vaccination strategies currently under investigation. Full article

(This article belongs to the Special Issue Vaccines Targeting Dendritic Cells)

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27 pages, 2149 KB

Open AccessEditor’s ChoiceArticle

Inflammatory and Humoral Immune Responses to Commercial Autogenous Salmonella Bacterin Vaccines in Light-Brown Leghorn Pullets: Primary and Secondary Vaccine Responses

by Chrysta N. Beck, Jossie M. Santamaria and Gisela F. Erf

Vaccines 2025, 13(3), 311; https://doi.org/10.3390/vaccines13030311 - 13 Mar 2025

Cited by 2 | Viewed by 1459

Abstract

Background/Objectives: Commercial poultry flocks undergo Salmonella vaccinations to manage salmonellosis outbreaks. Due to reports of severe injection site reactions to Salmonella bacterins, assessment of local inflammatory responses is necessary. The objective was to assess local inflammatory and systemic humoral immune responses to commercial [...] Read more.

Background/Objectives: Commercial poultry flocks undergo Salmonella vaccinations to manage salmonellosis outbreaks. Due to reports of severe injection site reactions to Salmonella bacterins, assessment of local inflammatory responses is necessary. The objective was to assess local inflammatory and systemic humoral immune responses to commercial autogenous Salmonella bacterin vaccines (SV1 or SV2) following primary or secondary intradermal (i.d.) vaccination in Light-Brown Leghorns (LBLs). Methods: LBL pullets received primary (14 wks) or secondary (19 wks) vaccination by i.d. growing feather (GF) pulp injection of SV1, SV2, Salmonella Enteritidis (SE) lipopolysaccharide (LPS), or water–oil–water emulsion (V). Local leukocyte levels and relative cytokine mRNA expression were monitored before (0 d) and at 6 h, 1 d, 2 d, 3 d, 5 d, and 7 d post-GF pulp injection (p.i.). Blood was collected through 28 d post-primary or -secondary vaccination, and SE-specific antibodies were quantified via ELISA. Results: Primary vaccine administration increased local heterophil and macrophage levels and increased IL-6 and IL-8 mRNA expressions at 6 h p.i., independent of treatment. Secondary administration extended these local immune activities through 3 d p.i. and included prolonged IL-17A mRNA expression. Primary and secondary GF-pulp injection with V resulted in rapid lymphocyte recruitment by 6 h p.i., comprised primarily of CD4⁺ and γδ T cells. SV1 and SV2 also produced a T-dependent systemic humoral immune response, as indicated by the IgM-to-IgG isotype switch, along with a memory phenotype in the secondary response. Conclusions: These commercial-killed Salmonella vaccines, when prepared in water–oil–water emulsions, stimulated prolonged innate and T helper (Th) 17-type inflammatory responses at the injection site and produced a classic systemic humoral immune response after a second vaccination. Further research is needed to determine if extended inflammation influences adaptive immune responses in eliminating Salmonella infection. Full article

(This article belongs to the Special Issue Novel Vaccine Designs to Enhance the Engagement of Innate and Adaptive Immunity)

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14 pages, 1648 KB

Open AccessEditor’s ChoiceArticle

Increase in Virus-Specific Mucosal Antibodies in the Upper Respiratory Tract Following Intramuscular Vaccination of Previously Exposed Horses Against Equine Herpesvirus Type-1/4

by Bettina Wagner, Christiane L. Schnabel and Alicia Rollins

Vaccines 2025, 13(3), 290; https://doi.org/10.3390/vaccines13030290 - 10 Mar 2025

Cited by 3 | Viewed by 1271

Abstract

Background/Objectives: Equine herpesvirus type-1 (EHV-1) enters through the upper respiratory tract (URT) and causes respiratory disease, abortions, and myeloencephalopathy in equids. Pre-existing immunity at the viral entry site, especially mucosal IgG4/7 antibodies, has recently been shown to correlate with protection from disease and [...] Read more.

Background/Objectives: Equine herpesvirus type-1 (EHV-1) enters through the upper respiratory tract (URT) and causes respiratory disease, abortions, and myeloencephalopathy in equids. Pre-existing immunity at the viral entry site, especially mucosal IgG4/7 antibodies, has recently been shown to correlate with protection from disease and incomplete viral replication at the URT. Here, we tested whether intramuscular (i.m.) vaccination with a commercial inactivated EHV-1/4 vaccine can induce mucosal antibodies (mucAbs) at the URT. Methods: Adult horses with complete EHV-1 vaccination and/or exposure histories were vaccinated i.m. six times within eight months. Before and after each vaccination, blood and nasal swab samples were obtained. Serum and mucAbs were measured in fluorescent bead-based EHV-1 assays. Results: All horses still had existing EHV-1 specific serum and mucAbs prior to vaccination, which were mainly composed of IgG4/7 antibody isotypes. Serum IgG4/7 significantly increased after the first vaccination and stayed high until the end of the study. An additional short-lasting serum IgG1 response was only induced by the first vaccine application. At the URT, mucAbs increased after five out of six i.m. vaccine injections. Like the systemic antibody response, mucAbs were dominated by IgG4/7 and a small IgG1 increase after the first vaccination. Conclusions: Our data emphasize that robust EHV-1 specific mucAb levels are obtained after i.m. vaccination with the inactivated EHV-1/4 vaccine used here. The findings have important implications for evaluating EHV-1/4 vaccines for their ability to induce and maintain protective mucosal IgG4/7 antibodies. Full article

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

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19 pages, 2598 KB

Open AccessEditor’s ChoiceArticle

Prime-Boost Vaccination Based on Nanospheres and MVA Encoding the Nucleoprotein of Crimean-Congo Hemorrhagic Fever Virus Elicits Broad Immune Responses

by Eva Calvo-Pinilla, Sandra Moreno, Natalia Barreiro-Piñeiro, Juana M. Sánchez-Puig, Rafael Blasco, José Martínez-Costas, Alejandro Brun and Gema Lorenzo

Vaccines 2025, 13(3), 291; https://doi.org/10.3390/vaccines13030291 - 10 Mar 2025

Cited by 2 | Viewed by 2213

Abstract

Background/Objectives: Crimean–Congo hemorrhagic fever virus (CCHFV) is an emerging, widely distributed zoonotic tick-borne pathogen. The virus causes severe disease in humans, and numerous wild and domestic animals act as reservoirs of it. Unfortunately, there are no effective therapies or safe vaccines commercialized [...] Read more.

Background/Objectives: Crimean–Congo hemorrhagic fever virus (CCHFV) is an emerging, widely distributed zoonotic tick-borne pathogen. The virus causes severe disease in humans, and numerous wild and domestic animals act as reservoirs of it. Unfortunately, there are no effective therapies or safe vaccines commercialized nowadays for this particular virus. As CCHF (Crimean–Congo hemorrhagic fever) is a serious threat to public health, there is an urgent need to investigate the development of safe and effective vaccination strategies further. Methods: In this work, we have employed two immunization platforms based on protein nanoparticles and a modified vaccinia Ankara (MVA) viral vector using the nucleoprotein (NP) as the target antigen. The humoral and cellular immune responses were characterized by ELISA, ICS, and cytokine measurement. Results: This work shows that a single dose of the vaccine candidates was not as immunogenic as the heterologous vaccination using nanoparticles and MVA. A prime with NP nanoparticles (NS-NP) and a boost with MVA-expressing NP were capable of triggering significant levels of humoral and cellular immune responses against CCHFV in mice. Conclusions: Our study shows that the NS-NP/MVA-NP vaccination strategy effectively elicits a robust humoral and cellular immune response in a mouse model, emphasizing its potential as a protective approach against CCHFV lineages. Full article

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

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19 pages, 2176 KB

Open AccessEditor’s ChoiceArticle

Evaluating the Immunogenicity of an Intranasal Microparticle Combination Vaccine for COVID-19 and Influenza

by Sharon Vijayanand, Smital Patil, Priyal Bagwe, Revanth Singh, Emmanuel Adediran and Martin J. D’Souza

Vaccines 2025, 13(3), 282; https://doi.org/10.3390/vaccines13030282 - 7 Mar 2025

Cited by 2 | Viewed by 2417

Abstract

Background: Infectious respiratory pathogens like SARS-CoV-2 and influenza frequently mutate, leading to the emergence of variants. This necessitates continuous updates to FDA-approved vaccines with booster shots targeting the circulating variants. Vaccine hesitancy and needle injections create inconvenience and contribute to reduced global vaccination [...] Read more.

Background: Infectious respiratory pathogens like SARS-CoV-2 and influenza frequently mutate, leading to the emergence of variants. This necessitates continuous updates to FDA-approved vaccines with booster shots targeting the circulating variants. Vaccine hesitancy and needle injections create inconvenience and contribute to reduced global vaccination rates. To address the burden of frequent painful injections, this manuscript explores the potential of non-invasive intranasal (IN) vaccine administration as an effective alternative to intramuscular (IM) shots. Further, as a proof-of-concept, an inactivated combination vaccine for COVID-19 and influenza was tested to eliminate the need for separate vaccinations. Methods: The methods involved encapsulating antigens and adjuvants in poly(lactic-co-glycolic acid) (PLGA) polymer matrices, achieving over 85% entrapment. The vaccine was evaluated in vitro for cytotoxicity and immunogenicity before being administered to 6–8-week-old Swiss Webster mice at weeks 0, 3, and 6. The mice were then assessed for antibody levels and cellular responses. Results: The intranasal microparticle (IN-MP) vaccine induced an innate immune response, autophagy, and were non-cytotoxic in vitro. In vivo, the vaccine led to high levels of virus-specific serum IgM, IgG, and IgA binding antibodies, as well as elevated IgG and IgA levels in the lung wash samples. The antibodies generated demonstrated neutralizing activity against the SARS-CoV-2 pseudovirus. Furthermore, the IN-MP vaccine prompted increased antigen-specific CD4⁺ and CD8⁺ T-cell responses in the vaccinated mice. Conclusions: The IN-MP combination vaccine produced immune responses comparable to or higher than the IM route, indicating its potential as an alternative to IM injections. Full article

(This article belongs to the Special Issue Innovating Vaccine Research in Mucosal Vaccines)

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20 pages, 3294 KB

Open AccessEditor’s ChoiceSystematic Review

Evaluating the Immunogenicity, Efficacy, and Effectiveness of Recombinant Zoster Vaccine for Global Public Health Policy

by Lucy R. Williams, Joachim Hombach and Melanie Marti

Vaccines 2025, 13(3), 250; https://doi.org/10.3390/vaccines13030250 - 27 Feb 2025

Cited by 3 | Viewed by 5415

Abstract

Background: Herpes zoster (HZ) is a painful neurocutaneous disease caused by the varicella-zoster virus. The recombinant zoster vaccine (RZV) is becoming increasingly incorporated into national vaccination schedules. We aimed to evaluate RZV from a global public health policy perspective. Methods: We [...] Read more.

Background: Herpes zoster (HZ) is a painful neurocutaneous disease caused by the varicella-zoster virus. The recombinant zoster vaccine (RZV) is becoming increasingly incorporated into national vaccination schedules. We aimed to evaluate RZV from a global public health policy perspective. Methods: We performed a rapid review of studies evaluating the immunogenicity, efficacy, and effectiveness of RZV for protection against HZ and associated complications. We searched PubMed for English-language studies published between 7 August 2012 and 30 September 2023. Included studies reported vaccine efficacy or effectiveness against HZ and HZ-associated complications. Immunogenicity studies were included if they contributed to the understanding of RZV protection over time and/or co-administration with other vaccines. HZ outcomes were stratified by socio-demographic and clinical variables. Results: From 405 identified publications, 33 were eligible for the study. Most studies were conducted in the US (N = 12), across North America (N = 10), and Europe (N = 5), or across multiple locations across North America, Latin America, and Asia–Australia (N = 6). Vaccine efficacy against HZ in immunocompetent populations ranged between 90% and 97%, while effectiveness ranged between 71% and 86%. Protection stayed above 70% for at least 10 years, with no significant differences by age or ethnicity. Conclusions: RZV is effective in reducing the risk of HZ and its associated complications. Protection is long-lasting and the vaccine is suitable for older and immunocompromised populations. However, the decision to incorporate the vaccine into national policies depends on additional factors (e.g., cost-effectiveness), which may be difficult to characterize without an understanding of the global disease burden. Full article

(This article belongs to the Special Issue 50 Years of Immunization—Steps Forward)

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14 pages, 3979 KB

Open AccessEditor’s ChoiceArticle

Pre-Existing Anti-Vector Immunity to Adenovirus-Inspired VLP Vaccines Shows an Adjuvant-Dependent Antagonism

by Salomé Gallet, Dalil Hannani, Sebastian Dergan-Dylon, Emilie Vassal-Stermann, Isabelle Bally, Christopher Chevillard, Daphna Fenel, Olivier Epaulard, Pascal Poignard and Pascal Fender

Vaccines 2025, 13(3), 238; https://doi.org/10.3390/vaccines13030238 - 25 Feb 2025

Viewed by 2400

Abstract

Background/Objectives: The use of virus-like particles (VLPs) in vaccinology has expanded significantly in recent years. VLPs have the advantage of being non-infectious while effectively stimulating B cell responses through the repetitive presentation of epitope motifs on their surface. Since VLPs are often derived [...] Read more.

Background/Objectives: The use of virus-like particles (VLPs) in vaccinology has expanded significantly in recent years. VLPs have the advantage of being non-infectious while effectively stimulating B cell responses through the repetitive presentation of epitope motifs on their surface. Since VLPs are often derived from human-infecting viruses, preexisting immunity may influence the immune response they elicit, warranting further investigation. Methods: We have developed a 60-mer VLP derived from human adenovirus type 3, a common pathogen. We investigated the impact of pre-existing adenovirus immunity on the immunization outcome against the linear S14P5 epitope of SARS-CoV-2, which was engineered into the particle (Ad-VLP-S14P5). To this end, antibody responses to S14P5 were evaluated following immunization with Ad-VLP-S14P5 in either naive or vector-primed mice. Results: Mice with pre-existing anti-vector immunity exhibited significantly greater anti-S14P5 antibody responses compared to vector-naive animals, demonstrating a beneficial impact of prior anti-adenovirus responses. However, the addition of an oil-in-water adjuvant for the immunizations abolished this positive impact, even leading to a deleterious effect of the pre-existing anti-vector immunity. Conclusions: The data suggest that the immune status against immunizing VLPs must be taken into consideration when designing immunization protocols. Importantly, the effects of prior immunity may vary depending on the nature of the protocol, including factors such as adjuvant use. Full article

(This article belongs to the Special Issue Development of Vaccines Based on Virus-Like Particles: The 3rd Edition)

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31 pages, 1245 KB

Open AccessEditor’s ChoiceReview

Advances and Challenges in Aeromonas hydrophila Vaccine Development: Immunological Insights and Future Perspectives

by Kavi R. Miryala and Banikalyan Swain

Vaccines 2025, 13(2), 202; https://doi.org/10.3390/vaccines13020202 - 18 Feb 2025

Cited by 21 | Viewed by 5369

Abstract

Aeromonas hydrophila presents a significant threat to global aquaculture due to its ability to infect freshwater and marine fish species, leading to substantial economic losses. Effective mitigation methods are essential to address these challenges. Vaccination has emerged as a promising strategy to reduce [...] Read more.

Aeromonas hydrophila presents a significant threat to global aquaculture due to its ability to infect freshwater and marine fish species, leading to substantial economic losses. Effective mitigation methods are essential to address these challenges. Vaccination has emerged as a promising strategy to reduce A. hydrophila infections; however, it faces several obstacles, including variability in immune responses, pathogen diversity, and environmental factors affecting vaccine efficacy. To enhance vaccine performance, researchers focus on adjuvants to boost immune responses and develop multivalent vaccines targeting multiple A. hydrophila strains. Tailoring vaccines to specific environmental conditions and optimizing vaccination schedules can further address the challenges posed by pathogen diversity and variable immune responses. This review provides an in-depth analysis of the immunological hurdles associated with A. hydrophila vaccine development. Current vaccine types—live attenuated, inactivated, subunit, recombinant, and DNA—exhibit diverse mechanisms for stimulating innate and adaptive immunity, with varying levels of success. Key focus areas include the potential of advanced adjuvants and nanoparticle delivery systems to overcome existing barriers. The review also highlights the importance of understanding host–pathogen interactions in guiding the development of more targeted and effective immune responses in fish. Complementary approaches, such as immunostimulants, probiotics, and plant-based extracts, are explored as adjuncts to vaccination in aquaculture health management. Despite notable progress, challenges remain in translating laboratory innovations into scalable, cost-effective solutions for aquaculture. Future directions emphasize the integration of advanced genomic and proteomic tools to identify novel antigen candidates and the need for industry-wide collaborations to standardize vaccine production and delivery. Addressing these challenges can unlock the potential of innovative vaccine technologies to safeguard fish health and promote sustainable aquaculture practices globally. Full article

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29 pages, 2354 KB

Open AccessEditor’s ChoiceReview

Molecular Farming for Immunization: Current Advances and Future Prospects in Plant-Produced Vaccines

by Dang-Khoa Vo and Kieu The Loan Trinh

Vaccines 2025, 13(2), 191; https://doi.org/10.3390/vaccines13020191 - 15 Feb 2025

Cited by 15 | Viewed by 12013

Abstract

Using plants as bioreactors, molecular farming has emerged as a versatile and sustainable platform for producing recombinant vaccines, therapeutic proteins, industrial enzymes, and nutraceuticals. This innovative approach leverages the unique advantages of plants, including scalability, cost-effectiveness, and reduced risk of contamination with human [...] Read more.

Using plants as bioreactors, molecular farming has emerged as a versatile and sustainable platform for producing recombinant vaccines, therapeutic proteins, industrial enzymes, and nutraceuticals. This innovative approach leverages the unique advantages of plants, including scalability, cost-effectiveness, and reduced risk of contamination with human pathogens. Recent advancements in gene editing, transient expression systems, and nanoparticle-based delivery technologies have significantly enhanced the efficiency and versatility of plant-based systems. Particularly in vaccine development, molecular farming has demonstrated its potential with notable successes such as Medicago’s Covifenz for COVID-19, illustrating the capacity of plant-based platforms to address global health emergencies rapidly. Furthermore, edible vaccines have opened new avenues in the delivery of vaccines, mainly in settings with low resources where the cold chain used for conventional logistics is a challenge. However, optimization of protein yield and stability, the complexity of purification processes, and regulatory hurdles are some of the challenges that still remain. This review discusses the current status of vaccine development using plant-based expression systems, operational mechanisms for plant expression platforms, major applications in the prevention of infectious diseases, and new developments, such as nanoparticle-mediated delivery and cancer vaccines. The discussion will also touch on ethical considerations, the regulatory framework, and future trends with respect to the transformative capacity of plant-derived vaccines in ensuring greater global accessibility and cost-effectiveness of the vaccination. This field holds great promise for the infectious disease area and, indeed, for applications in personalized medicine and biopharmaceuticals in the near future. Full article

(This article belongs to the Special Issue Production of Plant-Based Vaccines and Therapeutics)

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28 pages, 798 KB

Open AccessEditor’s ChoiceReview

Progress and Challenges in HIV-1 Vaccine Research: A Comprehensive Overview

by Alex C. Boomgarden and Chitra Upadhyay

Vaccines 2025, 13(2), 148; https://doi.org/10.3390/vaccines13020148 - 31 Jan 2025

Cited by 16 | Viewed by 22965

Abstract

The development of an effective HIV-1 vaccine remains a formidable challenge in biomedical research. Despite significant advancements in our understanding of HIV biology and pathogenesis, progress has been impeded by factors such as the virus's genetic diversity, high mutation rates, and its ability [...] Read more.

The development of an effective HIV-1 vaccine remains a formidable challenge in biomedical research. Despite significant advancements in our understanding of HIV biology and pathogenesis, progress has been impeded by factors such as the virus's genetic diversity, high mutation rates, and its ability to establish latent reservoirs. Recent innovative approaches, including mosaic vaccines and mRNA technology to induce broadly neutralizing antibodies, have shown promise. However, the efficacy of these vaccines has been modest, with the best results achieving approximately 30% effectiveness. Ongoing research emphasizes the necessity of a multifaceted strategy to overcome these obstacles and achieve a breakthrough in HIV-1 vaccine development. This review summarizes current approaches utilized to further understand HIV-1 biology and to create a global vaccine. We discuss the impact of these approaches on vaccine development for other diseases, including COVID-19, influenza, and Zika virus. Additionally, we highlight the specific limitations faced with each approach and present the methods researchers employ to overcome these challenges. These innovative techniques, which have demonstrated preclinical and clinical success, have advanced the field closer to the ultimate goal of developing a global HIV-1 vaccine. Leveraging these advancements will enable significant strides in combating HIV-1 and other infectious diseases, ultimately improving global health outcomes. Full article

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

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19 pages, 8275 KB

Open AccessEditor’s ChoiceArticle

Adenoviral Vector-Based Vaccine Expressing Hemagglutinin Stem Region with Autophagy-Inducing Peptide Confers Cross-Protection Against Group 1 and 2 Influenza A Viruses

by Wen-Chien Wang, Ekramy E. Sayedahmed, Marwa Alhashimi, Ahmed Elkashif, Vivek Gairola, Muralimanohara S. T. Murala, Suryaprakash Sambhara and Suresh K. Mittal

Vaccines 2025, 13(1), 95; https://doi.org/10.3390/vaccines13010095 - 20 Jan 2025

Cited by 5 | Viewed by 3003

Abstract

Background/Objectives: An effective universal influenza vaccine is urgently needed to overcome the limitations of current seasonal influenza vaccines, which are ineffective against mismatched strains and unable to protect against pandemic influenza. Methods: In this study, bovine and human adenoviral vector-based vaccine platforms were [...] Read more.

Background/Objectives: An effective universal influenza vaccine is urgently needed to overcome the limitations of current seasonal influenza vaccines, which are ineffective against mismatched strains and unable to protect against pandemic influenza. Methods: In this study, bovine and human adenoviral vector-based vaccine platforms were utilized to express various combinations of antigens. These included the H5N1 hemagglutinin (HA) stem region or HA2, the extracellular domain of matrix protein 2 of influenza A virus, HA signal peptide (SP), trimerization domain, excretory peptide, and the autophagy-inducing peptide C5 (AIP-C5). The goal was to identify the optimal combination for enhanced immune responses and cross-protection. Mice were immunized using a prime-boost strategy with heterologous adenoviral (Ad) vectors. Results: The heterologous Ad vectors induced robust HA stem-specific humoral and cellular immune responses in the immunized mice. Among the tested combinations, Ad vectors expressing SP + HA stem + AIP-C5 conferred significant protection against group 1 (H1N1 and H5N1) and group 2 (H3N2) influenza A viruses. This protection was demonstrated by lower lung viral titers and reduced morbidity and mortality. Conclusions: The findings support further investigation of heterologous Ad vaccine platforms expressing SP + HA stem + AIP-C5. This combination shows promise as a potential universal influenza vaccine, providing broader protection against influenza A viruses. Full article

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

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14 pages, 1446 KB

Open AccessEditor’s ChoiceArticle

Persistence of the Immune Response to an Intramuscular Bivalent (GI.1/GII.4) Norovirus Vaccine in Adults

by Geert Leroux-Roels, Robert L. Atmar, Jakob P. Cramer, Ian Escudero and Astrid Borkowski

Vaccines 2025, 13(1), 82; https://doi.org/10.3390/vaccines13010082 - 17 Jan 2025

Cited by 6 | Viewed by 3230

Abstract

Background: Major global economic and health burdens due to norovirus gastroenteritis could be addressed by an effective vaccine. Methods: In this study, 428 adult recipients of various compositions of the norovirus vaccine candidate, HIL-214, were followed for 5 years, to assess immune responses [...] Read more.

Background: Major global economic and health burdens due to norovirus gastroenteritis could be addressed by an effective vaccine. Methods: In this study, 428 adult recipients of various compositions of the norovirus vaccine candidate, HIL-214, were followed for 5 years, to assess immune responses to its virus-like particle antigens, GI.1 and GII.4c. Serum antibodies and peripheral-blood antibody-secreting cells (ASCs) were measured. This report focuses on the single-dose 15/50 (µg GI.1/GII.4c) composition, which had been selected for further clinical development. Results: For single-dose 15/50 recipients (N = 105), GI.1-specific and GII.4c-specific histoblood-group antigen-blocking (HBGA) antibodies appeared to have persisted to 5 years, waning from a peak at 4 to 8 weeks, and plateauing above baseline after 3 years. From 3 to 5 years, GI.1-specific GMTs ranged between 53 (95%CI, 40–71) and 60 (95%CI, 46–77; N = 69–97) and were approximately 2-fold above the baseline GMT (24 (95%CI, 20–28); N = 105). GII.4c-specific GMTs ranged between 103 (95%CI, 77–138) and 114 (95%CI, 86–152; N = 70–97) and were above baseline, but by less than 2-fold (70 (95%CI, 53–92); N = 105). Similar kinetics were observed for pan-Ig titers and ASCs in a subset. Similar kinetics were also observed for HBGA and pan-Ig titers in recipients of other 15/50 dosages. Conclusions: Immune responses to HIL-214 in adults appear to persist for five years. Full article

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

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15 pages, 272 KB

Open AccessEditor’s ChoiceReview

Pertussis Vaccination for Adults: An Updated Guide for Clinicians

by Kay Choong See

Vaccines 2025, 13(1), 60; https://doi.org/10.3390/vaccines13010060 - 11 Jan 2025

Cited by 8 | Viewed by 9865

Abstract

Pertussis, or whooping cough, is a highly contagious respiratory infection caused by the Gram-negative bacterium Bordetella pertussis. Although traditionally associated with children, pertussis is increasingly prevalent among adults, particularly those with comorbidities or weakened immune systems, where it can lead to severe [...] Read more.

Pertussis, or whooping cough, is a highly contagious respiratory infection caused by the Gram-negative bacterium Bordetella pertussis. Although traditionally associated with children, pertussis is increasingly prevalent among adults, particularly those with comorbidities or weakened immune systems, where it can lead to severe complications. Diagnosing pertussis in adults can be challenging due to its nonspecific symptoms, underreporting, and the limited sensitivity of available diagnostic tests. While treatment with macrolides is generally effective, it may not significantly alter the clinical course of the disease, and growing concerns about macrolide resistance are emerging. Vaccination remains the cornerstone of prevention, offering proven immunogenicity, efficacy, and safety. However, vaccination uptake remains low, partly due to limited patient awareness and insufficient prioritization by healthcare professionals. This review aims to provide clinicians with critical insights into pertussis epidemiology, vaccination strategies, and the latest guideline recommendations, empowering them to engage in meaningful discussions with adult patients and advocate for increased vaccination to combat this often-overlooked infection. Full article

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

18 pages, 2085 KB

Open AccessEditor’s ChoiceReview

Lipoprotein Signal Peptide as Adjuvants: Leveraging Lipobox-Driven TLR2 Activation in Modern Vaccine Design

by Muhammad Umar, Haroon Afzal, Asad Murtaza and Li-Ting Cheng

Vaccines 2025, 13(1), 36; https://doi.org/10.3390/vaccines13010036 - 2 Jan 2025

Cited by 4 | Viewed by 4151

Abstract

Toll-like receptor 2 (TLR2) signaling is a pivotal component of immune system activation, and it is closely linked to the lipidation of bacterial proteins. This lipidation is guided by bacterial signal peptides (SPs), which ensure the precise targeting and membrane anchoring of these [...] Read more.

Toll-like receptor 2 (TLR2) signaling is a pivotal component of immune system activation, and it is closely linked to the lipidation of bacterial proteins. This lipidation is guided by bacterial signal peptides (SPs), which ensure the precise targeting and membrane anchoring of these proteins. The lipidation process is essential for TLR2 recognition and the activation of robust immune responses, positioning lipidated bacterial proteins as potent immunomodulators and adjuvants for vaccines against bacterial-, viral-, and cancer-related antigens. The structural diversity and cleavage pathways of bacterial SPs are critical in determining lipidation efficiency and protein localization, influencing their immunogenic potential. Recent advances in bioinformatics have significantly improved the prediction of SP structures and cleavage sites, facilitating the rational design of recombinant lipoproteins optimized for immune activation. Moreover, the use of SP-containing lipobox motifs, as adjuvants to lipidate heterologous proteins, has expanded the potential of vaccines targeting a broad range of pathogens. However, challenges persist in expressing lipidated proteins, particularly within heterologous systems. These challenges can be addressed by optimizing expression systems, such as engineering E. coli strains for enhanced lipidation. Thus, lipoprotein signal peptides (SPs) demonstrate remarkable versatility as adjuvants in vaccine development, diagnostics, and immune therapeutics, highlighting their essential role in advancing immune-based strategies to combat diverse pathogens. Full article

(This article belongs to the Special Issue State-of-the-Art Vaccine Design)

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15 pages, 5522 KB

Open AccessEditor’s ChoiceArticle

Cell Wall Protein 2 as a Vaccine Candidate Protects Mice Against Clostridioides difficile Infection

by Shaohui Wang, Joshua Heuler, Jessica Bullock, Junling Qin, Soumyadeep Chakraborty, Agbendeh Lubem Nathaniel, Shifeng Wang and Xingmin Sun

Vaccines 2025, 13(1), 21; https://doi.org/10.3390/vaccines13010021 - 30 Dec 2024

Cited by 8 | Viewed by 1900

Abstract

Background/Objectives: Clostridioides difficile is a Gram-positive, spore-forming enteric pathogen that causes intestinal disorders, including inflammation and diarrhea, primarily through toxin production. Standard treatment options for C. difficile infection (CDI) involve a limited selection of antibiotics that are not fully effective, leading to high [...] Read more.

Background/Objectives: Clostridioides difficile is a Gram-positive, spore-forming enteric pathogen that causes intestinal disorders, including inflammation and diarrhea, primarily through toxin production. Standard treatment options for C. difficile infection (CDI) involve a limited selection of antibiotics that are not fully effective, leading to high recurrence rates. Vaccination presents a promising strategy for preventing both CDI and its recurrence. Cell wall protein 2 (Cwp2), a highly immunogenic and abundant surface-exposed C. difficile cell wall protein, plays an important role in the bacterium’s adherence in vitro. In this study, we aimed to analyze the homology and immunogenicity of Cwp2 and its protection efficacy as a vaccine candidate against CDI in mice. Methods: we conducted in silico analyses to assess the homology and immunogenicity of Cwp2, and we evaluated its potential as a vaccine candidate against CDI using a mouse model of immunization and infection. Results: Our in silico analyses predicted the immunogenic region (functional domain) of Cwp2 and revealed its high homology among various toxinotypes and ribotypes (R.T.s) or sequence types (S.T.s). Immunizations of mice with the Cwp2 functional domain (Cwp2_A) induced potent IgG/A antibody responses against Cwp2_A, protected mice from CDI, and reduced C. difficile spore and toxin levels in feces post-infection. Additionally, anti-Cwp2_A sera inhibited the binding of C. difficile vegetative cells to HCT8 cells. Conclusions: Our report demonstrates for the first time the potential of Cwp2_A as an effective vaccine candidate against CDI in mice. Full article

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16 pages, 615 KB

Open AccessEditor’s ChoiceReview

Durability of Adaptive Immunity in Immunocompetent and Immunocompromised Patients Across Different Respiratory Viruses: RSV, Influenza, and SARS-CoV-2

by Achilleas Livieratos, Lars Erik Schiro, Charalambos Gogos and Karolina Akinosoglou

Vaccines 2024, 12(12), 1444; https://doi.org/10.3390/vaccines12121444 - 22 Dec 2024

Cited by 5 | Viewed by 4908

Abstract

Background/Objectives. Research on respiratory virus immunity duration post-vaccination reveals variable outcomes. This study performed a literature review to assess the efficacy and longevity of immune protection post-vaccination against SARS-CoV-2, influenza, and respiratory syncytial virus (RSV), with a focus on immunocompromised populations. Specific objectives [...] Read more.

Background/Objectives. Research on respiratory virus immunity duration post-vaccination reveals variable outcomes. This study performed a literature review to assess the efficacy and longevity of immune protection post-vaccination against SARS-CoV-2, influenza, and respiratory syncytial virus (RSV), with a focus on immunocompromised populations. Specific objectives included examining humoral and cellular immune responses and exploring the impact of booster doses and hybrid immunity on extending protection. Methods. A literature review was conducted focusing on studies published from January 2014 to November 2024. The search targeted adaptive immunity post-vaccination, natural immunity, and hybrid immunity for SARS-CoV-2, influenza, and RSV. Selection criteria emphasized human populations, adaptive immunity outcomes, and immunocompromised individuals. The PICO framework guided the analysis, culminating in a detailed review of 30 studies. Results. SARS-CoV-2 vaccines exhibited robust initial antibody responses, which waned significantly within six months, necessitating frequent boosters. Influenza and RSV vaccines similarly showed declines in immunity, though some influenza vaccines demonstrated moderate durability. Hybrid immunity, arising from combined natural infection and vaccination, provided more resilient and lasting protection than vaccination alone, especially against emerging variants. Immunocompromised individuals consistently exhibited reduced durability in adaptive immune responses across all studied viruses. Challenges include rapid viral mutations, limiting the broad protection of current vaccines. Conclusions. Immune durability varies significantly across virus types and patient populations. Frequent boosters and hybrid immunity are critical to optimizing protection, particularly for vulnerable groups. The findings underscore the need for adaptable vaccination strategies and advancements in vaccine design to counter rapidly mutating respiratory pathogens effectively. Full article

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

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8 pages, 447 KB

Open AccessEditor’s ChoiceArticle

Immunoprophylaxis with MV140 Is Effective in the Reduction of Urinary Tract Infections—A Prospective Real-Life Study

by Filipe Abadesso Lopes, Miguel Miranda, André Ye, Joana Rodrigues, Paulo Pé-Leve, José Palma Reis and Ricardo Pereira e Silva

Vaccines 2024, 12(12), 1426; https://doi.org/10.3390/vaccines12121426 - 18 Dec 2024

Cited by 5 | Viewed by 5254

Abstract

Background/Objectives: Urinary tract infections (UTI) represent a highly frequent and debilitating disease. Immunoactive prophylaxis, such as the polyvalent bacterial whole-cell-based sublingual vaccine MV140, have been developed to avoid antibiotic use. However, the effectiveness of this tool in the Portuguese population is still unknown. [...] Read more.

Background/Objectives: Urinary tract infections (UTI) represent a highly frequent and debilitating disease. Immunoactive prophylaxis, such as the polyvalent bacterial whole-cell-based sublingual vaccine MV140, have been developed to avoid antibiotic use. However, the effectiveness of this tool in the Portuguese population is still unknown. This study aims at assessing the effectiveness of treatment with MV140 in a cohort of Portuguese patients presenting with recurrent UTIs. Methods: Prospective observational real-life study of 125 patients with complicated and uncomplicated recurrent UTIs treated with MV140. The primary outcome was a reduction in frequency and severity of UTIs after a follow-up of 12 months. Overall satisfaction, adverse events, and assessment of the effectiveness of MV140 in subgroups of patients with specific risk factors for UTIs were secondary outcomes. Results: In the 12 months after treatment outset, 38% of patients were UTI-free, 34% reported 1 or 2 UTI episodes, and the remaining 28% presented 3 or more UTIs, corresponding to a mean reduction of 3.20 (2.87–3.53, 95% C.I.; p < 0.001) UTI episodes per year per patient. The effectiveness of MV140 was the same regardless of sex, BMI, regular sexual activity, hypertension, diabetes mellitus, depression, paraplegia, performance of intermittent self-catheterization, indwelling bladder catheter, or previous use of other UTI-preventing vaccines. We observed a higher effectiveness in post-menopausal women compared to pre-menopausal (74.7% vs. 59.4%, respectively, p = 0.029). A total of 73% of patients reported a reduction in symptom severity or days of disease, and the mean global satisfaction was 7.52/10. Conclusions: MV140 demonstrated to be effective in the reduction rate of recurrent UTIs in a cohort of adult Portuguese patients. Full article

(This article belongs to the Section Vaccine Advancement, Efficacy and Safety)

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20 pages, 9291 KB

Open AccessEditor’s ChoiceArticle

Development Using Bioluminescence Imaging of a Recombinant Anguillid Herpesvirus 1 Vaccine Candidate Associated with Normal Replication In Vitro but Abortive Infection In Vivo

by Haiyan Zhang, Arun Sridhar, Natacha Delrez, Bo He, Sophie Fourny, Yuan Gao, Owen Donohoe and Alain F. C. Vanderplasschen

Vaccines 2024, 12(12), 1423; https://doi.org/10.3390/vaccines12121423 - 17 Dec 2024

Cited by 3 | Viewed by 2036

Abstract

Background/Objectives: Anguillid herpesvirus 1 (AngHV-1) (recently renamed Cyvirus anguillidallo 1) is the etiologic agent of a lethal disease that affects several eel species. It is thought to be one of the main infectious agents causing a population decline in wild eels and economic [...] Read more.

Background/Objectives: Anguillid herpesvirus 1 (AngHV-1) (recently renamed Cyvirus anguillidallo 1) is the etiologic agent of a lethal disease that affects several eel species. It is thought to be one of the main infectious agents causing a population decline in wild eels and economic loss within the eel aquaculture sector. To date, no vaccines are available against AngHV-1. Recently, we developed a safe and efficacious live attenuated recombinant vaccine against Cyprinid herpesvirus 3 (CyHV-3). This CyHV-3 recombinant vaccine encodes a deletion of ORF57. Orthologues of CyHV-3 ORF57 exist in Cyprinid herpesvirus 2 (CyHV-2, ORF57) and AngHV-1 (ORF35). Methods: In the present study, using recombinant strains and bioluminescent in vivo imaging, we investigated the effect of AngHV-1 ORF35 deletion on virus replication in vitro, virulence in vivo, and the potential of an AngHV-1 ORF35-deleted recombinant as a vaccine candidate for the mass vaccination of eels by immersion. With this goal in mind, we produced ORF35-deleted recombinants using two parental strains: a UK strain and a recombinant derived from the former strain by insertion of a Luciferase–GFP reporter cassette into a non-coding intergenic region. Results: Analyses of ORF35-deleted recombinants led to the following observations: (i) AngHV-1 ORF35 is not essential for viral growth in cell culture, and its deletion does not affect the production of extracellular virions despite reducing the size of viral plaque. (ii) In contrast to what has been observed for CyHV-3 ORF57 and CyHV-2 ORF57, in vivo bioluminescent analyses revealed that AngHV-1 ORF35 is an essential virulence factor and that its deletion led to abortive infection in vivo. (iii) Inoculation of the AngHV-1 ORF35-deleted recombinant by immersion induced a protective immune response against a wild-type challenge. This protection was shown to be dose-dependent and to rely on the infectivity of AngHV-1 ORF35-deleted virions. Conclusions: This study suggests that the AngHV-1 ORF35 protein has singular properties compared to its orthologues encoded by CyHV-2 and CyHV-3. It also supports the potential of AngHV-1 ORF35-deleted recombinants for the mass vaccination of eels by immersion. Full article

(This article belongs to the Special Issue Animal Herpesviruses)

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15 pages, 1318 KB

Open AccessEditor’s ChoiceReview

The Strategic Advisory Group of Experts (SAGE) on Immunization—Past, Present and Future

by Melanie Marti, Hanna Nohynek, Philippe Duclos, Katherine L. O’Brien and Joachim Hombach

Vaccines 2024, 12(12), 1402; https://doi.org/10.3390/vaccines12121402 - 12 Dec 2024

Cited by 7 | Viewed by 10265

Abstract

Background/Objectives: In November 1999, WHO established the Strategic Advisory Group of Experts (SAGE) on Immunization as a multidisciplinary group of experts to provide high-level recommendations on vaccines and immunization. Methods: This review provides an overview of SAGE’s work in the past 25 years. [...] Read more.

Background/Objectives: In November 1999, WHO established the Strategic Advisory Group of Experts (SAGE) on Immunization as a multidisciplinary group of experts to provide high-level recommendations on vaccines and immunization. Methods: This review provides an overview of SAGE’s work in the past 25 years. It further outlines the processes and methods currently used by SAGE and highlights some of its major achievements. Results: SAGE’s global policies have driven action toward eradication, elimination and disease control and addressed the optimization of vaccination and immunization. In total, 27 major policy positions on vaccines/vaccine-preventable diseases have guided global public health. During times of epidemics and pandemics, interim recommendations issued by SAGE have responded iteratively in real-time to provide evidence-driven response policies. SAGE is an adaptive advisory group that has modified its procedures and working approaches to meet the evolving challenges in public health and stay up-to-date with evolving scientific and guideline development standards. Conclusions: Over the last quarter century, SAGE has significantly contributed to shaping the immunization landscape. It has achieved and maintained a high level of integrity and credibility. The advisory group continues to be an authority in global public health, and its recommendations have profound implications for the health of individuals and populations across the globe. Full article

(This article belongs to the Special Issue 50 Years of Immunization—Steps Forward)

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24 pages, 1824 KB

Open AccessEditor’s ChoiceArticle

Safety, Immunogenicity, and Efficacy of a Recombinant Vesicular Stomatitis Virus Vectored Vaccine Against Severe Fever with Thrombocytopenia Syndrome Virus and Heartland Bandavirus

by Philip Hicks, Tomaz B. Manzoni, Jonna B. Westover, Raegan J. Petch, Brianne Roper, Brian B. Gowen and Paul Bates

Vaccines 2024, 12(12), 1403; https://doi.org/10.3390/vaccines12121403 - 12 Dec 2024

Cited by 7 | Viewed by 3255

Abstract

Background: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a recently emerged tickborne virus in east Asia with over 18,000 confirmed cases. With a high case fatality ratio, SFTSV has been designated a high priority pathogen by the WHO and the NIAID. Despite [...] Read more.

Background: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a recently emerged tickborne virus in east Asia with over 18,000 confirmed cases. With a high case fatality ratio, SFTSV has been designated a high priority pathogen by the WHO and the NIAID. Despite this, there are currently no approved therapies or vaccines to treat or prevent SFTS. Vesicular stomatitis virus (VSV) represents an FDA-approved vaccine platform that has been considered for numerous viruses due to its low sero-prevalence in humans, ease in genetic manipulation, and promiscuity in incorporating foreign glycoproteins into its virions. Methods: In this study, we developed a recombinant VSV (rVSV) expressing the SFTSV glycoproteins Gn/Gc (rVSV-SFTSV) and assessed its safety, immunogenicity, and efficacy in C57BL/6, Ifnar^−/−, and AG129 mice. Results: We demonstrate that rVSV-SFTSV is safe when given to immunocompromised animals and is not neuropathogenic when injected intracranially into young immunocompetent mice. Immunization of wild type (C57BL/6) and Ifnar^−/− mice with rVSV-SFTSV resulted in high levels of neutralizing antibodies and protection in a lethal SFTSV challenge model. Additionally, passive transfer of sera from immunized Ifnar^−/− mice into naïve animals was protective when given pre- or post-exposure. Finally, we demonstrate that immunization with rVSV-SFTSV cross protects AG129 mice against challenge with the closely related Heartland bandavirus despite negligible neutralizing titers to the virus. Conclusions: Taken together, these data suggest that rVSV-SFTSV is a promising vaccine candidate for SFTSV and Heartland bandavirus with a favorable safety profile. Full article

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34 pages, 3445 KB

Open AccessEditor’s ChoiceReview

Approaches to Enhance the Potency of Vaccines in Chickens

by Oenone Bodman-Harris, Christine S. Rollier and Munir Iqbal

Vaccines 2024, 12(12), 1337; https://doi.org/10.3390/vaccines12121337 - 27 Nov 2024

Cited by 9 | Viewed by 10313

Abstract

Outbreaks of avian pathogens such as Newcastle disease virus, avian influenza virus, and salmonella have a major impact on economies and food security worldwide. Some pathogens also pose a significant zoonotic potential, especially avian influenza viruses. Vaccination plays a key role in controlling [...] Read more.

Outbreaks of avian pathogens such as Newcastle disease virus, avian influenza virus, and salmonella have a major impact on economies and food security worldwide. Some pathogens also pose a significant zoonotic potential, especially avian influenza viruses. Vaccination plays a key role in controlling many poultry diseases, and there are many vaccines licenced in the United Kingdom for diseases of poultry caused by viruses, bacteria, and parasites. However, these vaccines often do not provide complete protection and can cause unwanted side effects. Several factors affect the potency of poultry vaccines, including the type of vaccination used, the mechanism of delivery, and the use of adjuvants. Advancements in technology have led to the study and development of novel vaccines and vaccine adjuvants for use in poultry. These induce stronger immune responses compared with current vaccine technology and have the potential to protect against multiple poultry diseases. This review aims to discuss the existing poultry vaccine technology; the effect of delivery mechanisms on vaccine efficacy; the use of current and novel adjuvants; the ability to target antigens to antigen-presenting cells; and the use of probiotics, multivalent vaccines, and nanotechnology to enhance the potency of poultry vaccines. Full article

(This article belongs to the Special Issue Vaccines Against Poultry Viruses)

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24 pages, 5421 KB

Open AccessEditor’s ChoiceArticle

Rapid Development of Modified Vaccinia Virus Ankara (MVA)-Based Vaccine Candidates Against Marburg Virus Suitable for Clinical Use in Humans

by Alina Tscherne, Georgia Kalodimou, Alexandra Kupke, Cornelius Rohde, Astrid Freudenstein, Sylvia Jany, Satendra Kumar, Gerd Sutter, Verena Krähling, Stephan Becker and Asisa Volz

Vaccines 2024, 12(12), 1316; https://doi.org/10.3390/vaccines12121316 - 24 Nov 2024

Cited by 4 | Viewed by 4183

Abstract

Background/Objectives: Marburg virus (MARV) is the etiological agent of Marburg Virus Disease (MVD), a rare but severe hemorrhagic fever disease with high case fatality rates in humans. Smaller outbreaks have frequently been reported in countries in Africa over the last few years, and [...] Read more.

Background/Objectives: Marburg virus (MARV) is the etiological agent of Marburg Virus Disease (MVD), a rare but severe hemorrhagic fever disease with high case fatality rates in humans. Smaller outbreaks have frequently been reported in countries in Africa over the last few years, and confirmed human cases outside Africa are, so far, exclusively imported by returning travelers. Over the previous years, MARV has also spread to non-endemic African countries, demonstrating its potential to cause epidemics. Although MARV-specific vaccines are evaluated in preclinical and clinical research, none have been approved for human use. Modified Vaccinia virus Ankara (MVA), a well-established viral vector used to generate vaccines against emerging pathogens, can deliver multiple antigens and has a remarkable clinical safety and immunogenicity record, further supporting its evaluation as a vaccine against MARV. The rapid availability of safe and effective MVA-MARV vaccine candidates would expand the possibilities of multi-factored intervention strategies in endemic countries. Methods: We have used an optimized methodology to rapidly generate and characterize recombinant MVA candidate vaccines that meet the quality requirements to proceed to human clinical trials. As a proof-of-concept for the optimized methodology, we generated two recombinant MVAs that deliver either the MARV glycoprotein (MVA-MARV-GP) or the MARV nucleoprotein (MVA-MARV-NP). Results: Infections of human cell cultures with recombinant MVA-MARV-GP and MVA-MARV-NP confirmed the efficient synthesis of MARV-GP and MARV-NP proteins in mammalian cells, which are non-permissive for MVA replication. Prime-boost immunizations in C57BL/6J mice readily induced circulating serum antibodies binding to recombinant MARV-GP and MARV-NP proteins. Moreover, the MVA-MARV-candidate vaccines elicited MARV-specific T-cell responses in C57BL/6J mice. Conclusions: We confirmed the suitability of our two backbone viruses MVA-mCherry and MVA-GFP in a proof-of-concept study to rapidly generate candidate vaccines against MARV. However, further studies are warranted to characterize the protective efficacy of these recombinant MVA-MARV vaccines in other preclinical models and to evaluate them as vaccine candidates in humans. Full article

(This article belongs to the Special Issue Strategies of Viral Vectors for Vaccine Development)

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14 pages, 10252 KB

Open AccessEditor’s ChoiceReview

Childhood Mandatory Vaccinations: Current Situation in European Countries and Changes Occurred from 2014 to 2024

by Sara Farina, Alessandra Maio, Maria Rosaria Gualano, Walter Ricciardi and Leonardo Villani

Vaccines 2024, 12(11), 1296; https://doi.org/10.3390/vaccines12111296 - 20 Nov 2024

Cited by 15 | Viewed by 12269

Abstract

Background/Objectives: Vaccination is one of the most effective public health interventions, preventing millions of deaths globally each year. However, vaccine hesitancy, driven by misinformation and reduced disease risk perception, has led to declining vaccination rates and the resurgence of vaccine-preventable diseases (VPDs) [...] Read more.

Background/Objectives: Vaccination is one of the most effective public health interventions, preventing millions of deaths globally each year. However, vaccine hesitancy, driven by misinformation and reduced disease risk perception, has led to declining vaccination rates and the resurgence of vaccine-preventable diseases (VPDs) in Europe. In response to this, countries have implemented various strategies, including mandatory and recommended vaccination programs. The objective of this study is to map the current European landscape of pediatric vaccination policies, and the variations that have occurred in the last decade. Methods: This rapid review was conducted on PubMed, Google, and the European Centre for Disease Prevention and Control website, to collect all vaccination schedules in EU/EEA countries in 2024 and all documents focusing on the introduction of mandatory vaccines during the last decade. Results: As of 2024, 13 countries had at least one mandatory pediatric vaccination, with France, Hungary, and Latvia requiring all but one vaccine. In contrast, 17 countries had no mandatory vaccinations, relying only on recommendations. Between 2014 and 2024, six countries (Croatia, France, Germany, Hungary, Italy, and Poland) introduced or extended mandatory vaccinations. Conclusions: European vaccination policies show significant variation. Effective programs depend on robust healthcare systems, public trust, and adaptable strategies to address vaccine hesitancy and the resurgence of VPDs. Full article

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

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12 pages, 2248 KB

Open AccessEditor’s ChoiceReview

Immune Checkpoint Inhibitors and Vaccination: Assessing Safety, Efficacy, and Synergistic Potential

by Jacob New, Luke Shenton, Radia Ksayer, Justin Wang, Karam Zakharia, Laura J. Nicholson and Amitabh C. Pandey

Vaccines 2024, 12(11), 1270; https://doi.org/10.3390/vaccines12111270 - 11 Nov 2024

Cited by 6 | Viewed by 5249

Abstract

Although immune checkpoint inhibitors (ICIs) have become predominant therapies for cancer, the safety and efficacy of combining ICIs with vaccinations remain areas of needed investigation. As ICIs gain broader clinical application, the relevance of current vaccination guidelines for cancer patients—largely developed in the [...] Read more.

Although immune checkpoint inhibitors (ICIs) have become predominant therapies for cancer, the safety and efficacy of combining ICIs with vaccinations remain areas of needed investigation. As ICIs gain broader clinical application, the relevance of current vaccination guidelines for cancer patients—largely developed in the context of cytotoxic therapies—becomes increasingly uncertain. Although data support the safety of combining inactivated influenza and mRNA SARS-CoV-2 vaccines with ICI therapy, comprehensive data on other infectious disease vaccines remain scarce. Notably, the combination of ICIs with infectious disease vaccines does not appear to exacerbate immune-related adverse events, despite the heightened cytokine activity observed. However, the efficacy of vaccines administered alongside ICIs in preventing infectious diseases remains poorly supported by robust evidence. Preliminary findings suggest a potential survival benefit in cancer patients receiving ICI therapy alongside influenza or SARS-CoV-2 vaccination, though the quality of evidence is currently low. Moreover, the synergistic potential of combining therapeutic cancer vaccines, particularly mRNA-based vaccines, with ICIs indicates promise but with a paucity of phase III data to confirm efficacy. This review critically examines the safety and efficacy of combining ICIs with both infectious disease vaccines and therapeutic cancer vaccines. While vaccination appears safe in patients undergoing ICI therapy, the impact on infectious disease prevention and cancer treatment outcomes warrants further rigorous investigation. Full article

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15 pages, 706 KB

Open AccessEditor’s ChoiceArticle

Lessons from Recent Measles Post-Campaign Coverage Surveys Worldwide

by M. Carolina Danovaro-Holliday, Mitsuki Koh, Claudia Steulet, Dale A. Rhoda and Mary Kay Trimner

Vaccines 2024, 12(11), 1257; https://doi.org/10.3390/vaccines12111257 - 6 Nov 2024

Cited by 3 | Viewed by 3065

Abstract

Background: Measles elimination strategies include supplementary immunization activities (SIAs) to rapidly fill immunity gaps. Post-campaign coverage surveys (PCCSs) are recommended to assess SIA coverage. We characterized selected PCCSs performed following recent SIAs, highlighting specific challenges and strengths, and provide recommendations for improvement. Methods: [...] Read more.

Background: Measles elimination strategies include supplementary immunization activities (SIAs) to rapidly fill immunity gaps. Post-campaign coverage surveys (PCCSs) are recommended to assess SIA coverage. We characterized selected PCCSs performed following recent SIAs, highlighting specific challenges and strengths, and provide recommendations for improvement. Methods: We extracted national SIA data from the global measles/MR SIA database for the period of 2020–2023 and reviewed PCCS reports available at the World Health Organization headquarters. We extracted selected information on PCCS implementation, including information about the implementer, sampling, and main results. Results: Only 15 of 66 countries (23%) with a national-level SIA performed since 2020 had a PCCS report available. We reviewed those reports, plus six more, following three 2019 SIAs with a delayed PCCS and two PCCSs following large subnational SIAs (Kenya 2021 and Yemen 2023). All 24 PCCS reports available were from Gavi-eligible countries, with 15 from South Saharan Africa (Cameroon, the Democratic Republic of the Congo, and Ethiopia had two PCCSs). Eleven (45.8%) PCCSs were conducted within three months of the end of the SIA. All included sampling information and most had percentage of participation. Description of the interviewers’ profiles varied but was limited. PCCS coverage was lower than administrative data in all but two instances. All PCCSs collected data on previous measles vaccination status that would allow exploring indicators on the SIA reaching previously measles zero-dose children. Of the 12 PCCSs reporting coverage among previously measles zero-dose children, nine reported coverage among this group of more than 50% (range: 12% and 91.6%). Conclusion: Even though a PCCS following an SIA is recommended and a requirement in Gavi-supported countries, most SIAs are not followed by a PCCS and, when performed, the timeliness of survey implementation needs improvement. Recent PCCSs were independently conducted and reports included basic survey information, but analysis and presentation of survey results vary particularly for measles zero-dose-related indicators. More guidance and technical support on how to implement PCCSs, including standardization of reports and more in-depth PCCS analyses, may help improve reporting and use of available PCCS data. Full article

(This article belongs to the Special Issue A World without Measles and Rubella: Meeting the Regional Elimination Targets on the Path to Global Eradication)

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17 pages, 2454 KB

Open AccessEditor’s ChoiceReview

Impact of Infections During Pregnancy on Transplacental Antibody Transfer

by Celeste Coler, Elana King-Nakaoka, Emma Every, Sophia Chima, Ashley Vong, Briana Del Rosario, Roslyn VanAbel and Kristina M. Adams Waldorf

Vaccines 2024, 12(10), 1199; https://doi.org/10.3390/vaccines12101199 - 21 Oct 2024

Cited by 8 | Viewed by 8531

Abstract

Vaccination in pregnancy is important to protect the mother and fetus from infectious diseases. The transfer of maternal antibodies across the placenta during pregnancy can continue to protect the neonate for several months after birth while the neonatal adaptive immune system develops. Several [...] Read more.

Vaccination in pregnancy is important to protect the mother and fetus from infectious diseases. The transfer of maternal antibodies across the placenta during pregnancy can continue to protect the neonate for several months after birth while the neonatal adaptive immune system develops. Several pathogens have been shown to impair the transplacental transfer of maternal antibodies, including human immunodeficiency virus, malaria, the severe acute respiratory syndrome coronavirus 2, and cytomegalovirus. This review discusses the mechanisms contributing to decreased transplacental antibody transfer in the setting of maternal infections, such as changes in antibody glycosylation profile, maternal hypergammaglobulinemia, and placental injury. The frequency of epidemics is increasing, and pregnant people are more likely to become exposed to novel pathogens now than they were in the past. Understanding the mechanisms by which infectious diseases impair maternal–fetal antibody transfer is important for pandemic preparedness to maximize the impact of maternal vaccination for child health. Full article

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16 pages, 1172 KB

Open AccessEditor’s ChoiceReview

T-Cell Epitope-Based Vaccines: A Promising Strategy for Prevention of Infectious Diseases

by Xin Song, Yongfeng Li, Hongxia Wu, Hua-Ji Qiu and Yuan Sun

Vaccines 2024, 12(10), 1181; https://doi.org/10.3390/vaccines12101181 - 17 Oct 2024

Cited by 25 | Viewed by 8902

Abstract

With the development of novel vaccine strategies, T-cell epitope-based vaccines have become promising prophylactic and therapeutic tools against infectious diseases that cannot be controlled via traditional vaccines. T-cell epitope-based vaccines leverage specific immunogenic peptides to elicit protective T-cell responses against infectious pathogens. Compared [...] Read more.

With the development of novel vaccine strategies, T-cell epitope-based vaccines have become promising prophylactic and therapeutic tools against infectious diseases that cannot be controlled via traditional vaccines. T-cell epitope-based vaccines leverage specific immunogenic peptides to elicit protective T-cell responses against infectious pathogens. Compared to traditional vaccines, they provide superior efficacy and safety, minimizing the risk of adverse side effects. In this review, we summarized and compared the prediction and identification methods of T-cell epitopes. By integrating bioinformatic prediction and experimental validation, efficient and precise screening of T-cell epitopes can be achieved. Importantly, we delved into the development approaches to diverse T-cell epitope-based vaccines, comparing their merits and demerits, as well as discussing the prevalent challenges and perspectives in their applications. This review offers fresh perspectives for the formulation of safe and efficacious epitope-based vaccines for the devastating diseases against which no vaccines are currently available. Full article

(This article belongs to the Special Issue Immunization Strategies for Animal Health)

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20 pages, 4599 KB

Open AccessEditor’s ChoiceReview

Recent Advances in Lipid Nanoparticles and Their Safety Concerns for mRNA Delivery

by Jialiang Wang, Yaopeng Ding, Kellie Chong, Meng Cui, Zeyu Cao, Chenjue Tang, Zhen Tian, Yuping Hu, Yu Zhao and Shaoyi Jiang

Vaccines 2024, 12(10), 1148; https://doi.org/10.3390/vaccines12101148 - 8 Oct 2024

Cited by 118 | Viewed by 25249

Abstract

Introduction: The advent of lipid nanoparticles (LNPs) as a delivery platform for mRNA therapeutics has revolutionized the biomedical field, particularly in treating infectious diseases, cancer, genetic disorders, and metabolic diseases. Recent Advances in Therapeutic LNPs: LNPs, composed of ionizable lipids, phospholipids, cholesterol, and [...] Read more.

Introduction: The advent of lipid nanoparticles (LNPs) as a delivery platform for mRNA therapeutics has revolutionized the biomedical field, particularly in treating infectious diseases, cancer, genetic disorders, and metabolic diseases. Recent Advances in Therapeutic LNPs: LNPs, composed of ionizable lipids, phospholipids, cholesterol, and polyethylene glycol (PEG) lipids, facilitate efficient cellular uptake and cytosolic release of mRNA while mitigating degradation by nucleases. However, as synthetic entities, LNPs face challenges that alter their therapeutic efficacy and safety concerns. Toxicity/Reactogenicity/Immunogenicity: This review provides a comprehensive overview of the latest advancements in LNP research, focusing on preclinical safety assessments encompassing toxicity, reactogenicity, and immunogenicity. Summary and Outlook: Additionally, it outlines potential strategies for addressing these challenges and offers insights into future research directions for enhancing the application of LNPs in mRNA therapeutics. Full article

(This article belongs to the Special Issue Biotechnologies Applied in Vaccine Research)

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19 pages, 2943 KB

Open AccessEditor’s ChoiceReview

Ferritin Vaccine Platform for Animal and Zoonotic Viruses

by Sohrab Ahmadivand, Robert Fux and Dušan Palić

Vaccines 2024, 12(10), 1112; https://doi.org/10.3390/vaccines12101112 - 27 Sep 2024

Cited by 16 | Viewed by 6333

Abstract

Viral infections in animals continue to pose a significant challenge, affecting livestock health, welfare, and food safety, and, in the case of zoonotic viruses, threatening global public health. The control of viral diseases currently relies on conventional approaches such as inactivated or attenuated [...] Read more.

Viral infections in animals continue to pose a significant challenge, affecting livestock health, welfare, and food safety, and, in the case of zoonotic viruses, threatening global public health. The control of viral diseases currently relies on conventional approaches such as inactivated or attenuated vaccines produced via platforms with inherent limitations. Self-assembling ferritin nanocages represent a novel vaccine platform that has been utilized for several viruses, some of which are currently undergoing human clinical trials. Experimental evidence also supports the potential of this platform for developing commercial vaccines for veterinary viruses. In addition to improved stability and immunogenicity, ferritin-based vaccines are safe and DIVA-compatible, and can be rapidly deployed in response to emerging epidemics or pandemics. This review discusses the structural and functional properties of ferritin proteins, followed by an overview of the design and production of ferritin-based vaccines, the mechanisms of immune responses, and their applications in developing vaccines against animal and zoonotic viruses. Full article

(This article belongs to the Special Issue Vaccine Development for Emerging and Zoonotic Diseases)

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35 pages, 2230 KB

Open AccessEditor’s ChoiceReview

Navigating the Landscape of B Cell Mediated Immunity and Antibody Monitoring in SARS-CoV-2 Vaccine Efficacy: Tools, Strategies and Clinical Trial Insights

by Sophie O’Reilly, Joanne Byrne, Eoin R. Feeney, Patrick W. G. Mallon and Virginie Gautier

Vaccines 2024, 12(10), 1089; https://doi.org/10.3390/vaccines12101089 - 24 Sep 2024

Cited by 6 | Viewed by 4061

Abstract

Correlates of Protection (CoP) are biomarkers above a defined threshold that can replace clinical outcomes as primary endpoints, predicting vaccine effectiveness to support the approval of new vaccines or follow up studies. In the context of COVID-19 vaccination, CoPs can help address challenges [...] Read more.

Correlates of Protection (CoP) are biomarkers above a defined threshold that can replace clinical outcomes as primary endpoints, predicting vaccine effectiveness to support the approval of new vaccines or follow up studies. In the context of COVID-19 vaccination, CoPs can help address challenges such as demonstrating vaccine effectiveness in special populations, against emerging SARS-CoV-2 variants or determining the durability of vaccine-elicited immunity. While anti-spike IgG titres and viral neutralising capacity have been characterised as CoPs for COVID-19 vaccination, the contribution of other components of the humoral immune response to immediate and long-term protective immunity is less well characterised. This review examines the evidence supporting the use of CoPs in COVID-19 clinical vaccine trials, and how they can be used to define a protective threshold of immunity. It also highlights alternative humoral immune biomarkers, including Fc effector function, mucosal immunity, and the generation of long-lived plasma and memory B cells and discuss how these can be applied to clinical studies and the tools available to study them. Full article

(This article belongs to the Special Issue Immune Effectiveness of COVID-19 Vaccines)

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17 pages, 616 KB

Open AccessEditor’s ChoiceReview

Hybrid Immunity against SARS-CoV-2 Variants: A Narrative Review of the Literature

by Panagiota Tsagkli, Maria Geropeppa, Ioanna Papadatou and Vana Spoulou

Vaccines 2024, 12(9), 1051; https://doi.org/10.3390/vaccines12091051 - 14 Sep 2024

Cited by 13 | Viewed by 9588

Abstract

The emergence of SARS-CoV-2 led to a global health crisis and the burden of the disease continues to persist. The rapid development and emergency authorization of various vaccines, including mRNA-based vaccines, played a pivotal role in mitigating severe illness and mortality. However, rapid [...] Read more.

The emergence of SARS-CoV-2 led to a global health crisis and the burden of the disease continues to persist. The rapid development and emergency authorization of various vaccines, including mRNA-based vaccines, played a pivotal role in mitigating severe illness and mortality. However, rapid viral mutations, leading to several variants of concern, challenged vaccine effectiveness, particularly concerning immune evasion. Research on immunity, both from natural infection and vaccination, revealed that while neutralizing antibodies provide protection against infection, their effect is short-lived. The primary defense against severe COVID-19 is derived from the cellular immune response. Hybrid immunity, developed from a combination of natural infection and vaccination, offers enhanced protection, with convalescent vaccinated individuals showing significantly higher levels of neutralizing antibodies. As SARS-CoV-2 continues to evolve, understanding the durability and breadth of hybrid immunity becomes crucial. This narrative review examines the latest data on humoral and cellular immunity from both natural infection and vaccination, discussing how hybrid immunity could inform and optimize future vaccination strategies in the ongoing battle against COVID-19 and in fear of a new pandemic. Full article

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

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18 pages, 319 KB

Open AccessEditor’s ChoiceReview

HIV Vaccine Development at a Crossroads: New B and T Cell Approaches

by Ramesh Govindan and Kathryn E. Stephenson

Vaccines 2024, 12(9), 1043; https://doi.org/10.3390/vaccines12091043 - 12 Sep 2024

Cited by 8 | Viewed by 8687

Abstract

Despite rigorous scientific efforts over the forty years since the onset of the global HIV pandemic, a safe and effective HIV-1 vaccine remains elusive. The challenges of HIV vaccine development have proven immense, in large part due to the tremendous sequence diversity of [...] Read more.

Despite rigorous scientific efforts over the forty years since the onset of the global HIV pandemic, a safe and effective HIV-1 vaccine remains elusive. The challenges of HIV vaccine development have proven immense, in large part due to the tremendous sequence diversity of HIV and its ability to escape from antiviral adaptive immune responses. In recent years, several phase 3 efficacy trials have been conducted, testing a similar hypothesis, e.g., that non-neutralizing antibodies and classical cellular immune responses could prevent HIV-1 acquisition. These studies were not successful. As a result, the field has now pivoted to bold novel approaches, including sequential immunization strategies to drive the generation of broadly neutralizing antibodies and human CMV-vectored vaccines to elicit MHC-E-restricted CD8+ T cell responses. Many of these vaccine candidates are now in phase 1 trials, with early promising results. Full article

(This article belongs to the Special Issue T-cell Immunity and Viral Pathogenicity on Vaccine Efficacy)

21 pages, 3794 KB

Open AccessEditor’s ChoiceReview

The Major Role of T Regulatory Cells in the Efficiency of Vaccination in General and Immunocompromised Populations: A Review

by Stanislaw Stepkowski, Dulat Bekbolsynov, Jared Oenick, Surina Brar, Beata Mierzejewska, Michael A. Rees and Obi Ekwenna

Vaccines 2024, 12(9), 992; https://doi.org/10.3390/vaccines12090992 - 30 Aug 2024

Cited by 5 | Viewed by 4357

Abstract

Since their conception with the smallpox vaccine, vaccines used worldwide have mitigated multiple pandemics, including the recent COVID-19 outbreak. Insightful studies have uncovered the complexities of different functional networks of CD4 T cells (T helper 1 (Th1); Th2, Th17) and CD8 T cells [...] Read more.

Since their conception with the smallpox vaccine, vaccines used worldwide have mitigated multiple pandemics, including the recent COVID-19 outbreak. Insightful studies have uncovered the complexities of different functional networks of CD4 T cells (T helper 1 (Th1); Th2, Th17) and CD8 T cells (T cytotoxic; Tc), as well as B cell (B^IgM, B^IgG, B^IgA and B^IgE) subsets, during the response to vaccination. Both T and B cell subsets form central, peripheral, and tissue-resident subsets during vaccination. It has also become apparent that each vaccination forms a network of T regulatory subsets, namely CD4+ CD25+ Foxp3⁺ T regulatory (Treg) cells and interleukin-10 (IL-10)-producing CD4+ Foxp3⁻ T regulatory 1 (Tr1), as well as many others, which shape the quality/quantity of vaccine-specific IgM, IgG, and IgA antibody production. These components are especially critical for immunocompromised patients, such as older individuals and allograft recipients, as their vaccination may be ineffective or less effective. This review focuses on considering how the pre- and post-vaccination Treg/Tr1 levels influence the vaccination efficacy. Experimental and clinical work has revealed that Treg/Tr1 involvement evokes different immune mechanisms in diminishing vaccine-induced cellular/humoral responses. Alternative steps may be considered to improve the vaccination response, such as increasing the dose, changing the delivery route, and/or repeated booster doses of vaccines. Vaccination may be combined with anti-CD25 (IL-2Rα chain) or anti-programmed cell death protein 1 (PD-1) monoclonal antibodies (mAb) to decrease the Tregs and boost the T/B cell immune response. All of these data and strategies for immunizations are presented and discussed, aiming to improve the efficacy of vaccination in humans and especially in immunocompromised and older individuals, as well as organ transplant patients. Full article

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14 pages, 3226 KB

Open AccessEditor’s ChoiceArticle

Immunogenicity and Protective Efficacy of a Multi-Antigen Mycobacterium tuberculosis Subunit Vaccine in Mice

by Annuurun Nisa, Rachel Pinto, Warwick J. Britton, James A. Triccas and Claudio Counoupas

Vaccines 2024, 12(9), 997; https://doi.org/10.3390/vaccines12090997 - 30 Aug 2024

Cited by 4 | Viewed by 7019

Abstract

There is an urgent need for an effective TB vaccine capable of controlling both acute and chronic Mycobacterium tuberculosis infection in populations with diverse genetic backgrounds. In this study, we characterised the immunogenicity and protective efficacy of a novel protein-in-adjuvant subunit vaccine. The [...] Read more.

There is an urgent need for an effective TB vaccine capable of controlling both acute and chronic Mycobacterium tuberculosis infection in populations with diverse genetic backgrounds. In this study, we characterised the immunogenicity and protective efficacy of a novel protein-in-adjuvant subunit vaccine. The protein component is a fusion protein of three different M. tuberculosis antigens, which we termed CysVac5: CysD, a major component of the M. tuberculosis sulfate activation pathway that is highly expressed during the chronic stage of M. tuberculosis infection, is fused with two major secreted mycobacterial antigens, Ag85B and MPT83. Vaccination of C57BL/6 mice with CysVac5, formulated in a monophosphoryl lipid A (MPLA) and dimethyldioctadecylammonium (DDA) adjuvant combination, resulted in the potent generation of polyfunctional CD4⁺ T cells secreting multiple cytokines, including IFN-γ, IL-2, TNF and IL-17, against each of the three components of the fusion protein. Furthermore, vaccination with CysVac5-MPLA/DDA conferred significant protection against infection in mouse lungs, which was greater than that afforded by BCG at extended time points post-challenge. The generation of antigen-specific and protective immunity was also observed in CysVac5 vaccinated BALB/c mice, indicating the vaccine could display efficacy across multiple genetic backgrounds. These results indicate that the CysVac5 vaccine has broad immunogenicity, is effective in controlling both acute and chronic phases of M. tuberculosis infection in mice, and warrants further investigation to assess its potential to control pulmonary TB. Full article

(This article belongs to the Special Issue Tuberculosis Vaccines and Host-Directed Therapies)

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12 pages, 940 KB

Open AccessEditor’s ChoiceArticle

The Influence of SARS-CoV-2 Vaccination on the Mortality and Outcomes of Patients with Both Myocardial Infarction and COVID-19

by Eugeniusz Hrycek, Anna Walawska-Hrycek, Krzysztof Milewski, Przemysław Nowakowski, Piotr Buszman and Aleksander Żurakowski

Vaccines 2024, 12(9), 983; https://doi.org/10.3390/vaccines12090983 - 29 Aug 2024

Cited by 3 | Viewed by 4380

Abstract

Background: This multi-site retrospective analysis with a control group was devised to evaluate the impact of prophylactic SARS-CoV-2 vaccination the on outcomes of myocardial infarction (MI) patients with confirmed COVID-19. Methods: An overall of 129 subjects who had been diagnosed with COVID-19 and [...] Read more.

Background: This multi-site retrospective analysis with a control group was devised to evaluate the impact of prophylactic SARS-CoV-2 vaccination the on outcomes of myocardial infarction (MI) patients with confirmed COVID-19. Methods: An overall of 129 subjects who had been diagnosed with COVID-19 and MI were included in the analysis and were divided into the study group (44 vaccinated patients) and the control group (85 non-vaccinated comparable patients). The primary outcome measure was defined as the time until in-hospital death, while the secondary outcome measure was defined as the time until death outside the hospital setting. Results: According to in-hospital mortality analysis, 1 (2.27%) subject died in the study group, whereas a total of 19 (22.4%) subjects died among the controls (OR = 0.08; CI: 0.001–0.553; p = 0.023). The impact of vaccination on the in-hospital outcomes of patients treated for COVID-19 and MI was further confirmed using Cox regression analysis (HR: 0.1 CI: 0.01–0.77; p = 0.026). The observed difference was the absence of respiratory failure requiring mechanical ventilation in the study group, whereas it was observed in 14 (16.47%) patients in the control group. During out-of-hospital observation, there were no observed differences in mortality (OR: 1.56; 95% CI: 0.21–11.52; p = 0.66). Conclusions: The complete prophylactic SARS-CoV-2 vaccination course demonstrates a protective role in patients undergoing treatment for MI with confirmed COVID-19 during in-hospital observation. Full article

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

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33 pages, 1253 KB

Open AccessEditor’s ChoiceReview

A Comprehensive Review on Porcine Reproductive and Respiratory Syndrome Virus with Emphasis on Immunity

by Jorian Fiers, Ann Brigitte Cay, Dominiek Maes and Marylène Tignon

Vaccines 2024, 12(8), 942; https://doi.org/10.3390/vaccines12080942 - 22 Aug 2024

Cited by 20 | Viewed by 10429

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important pathogens in pig production worldwide and responsible for enormous production and economic losses. PRRSV infection in gestating gilts and sows induces important reproductive failure. Additionally, respiratory distress is observed in [...] Read more.

Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important pathogens in pig production worldwide and responsible for enormous production and economic losses. PRRSV infection in gestating gilts and sows induces important reproductive failure. Additionally, respiratory distress is observed in infected piglets and fattening pigs, resulting in growth retardation and increased mortality. Importantly, PRRSV infection interferes with immunity in the respiratory tract, making PRRSV-infected pigs more susceptible to opportunistic secondary pathogens. Despite the availability of commercial PRRSV vaccines for more than three decades, control of the disease remains a frustrating and challenging task. This paper provides a comprehensive overview of PRRSV, covering its history, economic and scientific importance, and description of the viral structure and genetic diversity. It explores the virus’s pathogenesis, including cell tropism, viral entry, replication, stages of infection and epidemiology. It reviews the porcine innate and adaptative immune responses to comprehend the modulation mechanisms employed by PRRS for immune evasion. Full article

(This article belongs to the Special Issue Immunization Strategies for Animal Health)

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20 pages, 824 KB

Open AccessEditor’s ChoiceReview

Treatments and the Perspectives of Developing a Vaccine for Chagas Disease

by Priscila Silva Grijó Farani, Kathryn Marie Jones and Cristina Poveda

Vaccines 2024, 12(8), 870; https://doi.org/10.3390/vaccines12080870 - 1 Aug 2024

Cited by 10 | Viewed by 4735

Abstract

Chagas disease (CD) treatment and vaccine development are critical due to the significant health burden caused by the disease, especially in Latin America. Current treatments include benznidazole and nifurtimox, which are most effective in the acute phase of the disease but less so [...] Read more.

Chagas disease (CD) treatment and vaccine development are critical due to the significant health burden caused by the disease, especially in Latin America. Current treatments include benznidazole and nifurtimox, which are most effective in the acute phase of the disease but less so in the chronic phase, often with significant side effects. Here, using the available literature, we summarize the progress in vaccine development and new treatments that promise to reduce CD incidence and improve the quality of life for those at risk, particularly in endemic regions. New treatment options, such as posaconazole and fexinidazole, are being explored to improve efficacy and reduce adverse effects. Vaccine development for CD remains a high priority. The complex life stages and genetic diversity of Trypanosoma cruzi present challenges, but several promising vaccine candidates are under investigation. These efforts focus on stimulating a protective immune response through various innovative approaches. Full article

(This article belongs to the Section Vaccines Against Tropical and Other Infectious Diseases)

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26 pages, 989 KB

Open AccessEditor’s ChoiceReview

Immunity to Sexually Transmitted Bacterial Infections of the Female Genital Tract: Toward Effective Vaccines

by Kacy S. Yount and Toni Darville

Vaccines 2024, 12(8), 863; https://doi.org/10.3390/vaccines12080863 - 1 Aug 2024

Cited by 4 | Viewed by 4603

Abstract

Sexually transmitted infections (STIs) caused by bacterial pathogens Chlamydia trachomatis, Neisseria gonorrhoeae, and Treponema pallidum present significant public health challenges. These infections profoundly impact reproductive health, leading to pelvic inflammatory disease, infertility, and increased susceptibility to other infections. Prevention measures, including [...] Read more.

Sexually transmitted infections (STIs) caused by bacterial pathogens Chlamydia trachomatis, Neisseria gonorrhoeae, and Treponema pallidum present significant public health challenges. These infections profoundly impact reproductive health, leading to pelvic inflammatory disease, infertility, and increased susceptibility to other infections. Prevention measures, including antibiotic treatments, are limited by the often-asymptomatic nature of these infections, the need for repetitive and continual screening of sexually active persons, antibiotic resistance for gonorrhea, and shortages of penicillin for syphilis. While vaccines exist for viral STIs like human papillomavirus (HPV) and hepatitis B virus (HBV), there are no vaccines available for bacterial STIs. This review examines the immune responses in the female genital tract to these bacterial pathogens and the implications for developing effective vaccines against bacterial STIs. Full article

(This article belongs to the Section Vaccines, Clinical Advancement, and Associated Immunology)

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18 pages, 1351 KB

Open AccessEditor’s ChoiceReview

Inequality in Childhood Immunization Coverage: A Scoping Review of Data Sources, Analyses, and Reporting Methods

by Carrie Lyons, Devaki Nambiar, Nicole E. Johns, Adrien Allorant, Nicole Bergen and Ahmad Reza Hosseinpoor

Vaccines 2024, 12(8), 850; https://doi.org/10.3390/vaccines12080850 - 29 Jul 2024

Cited by 11 | Viewed by 7267

Abstract

Immunization through vaccines among children has contributed to improved childhood survival and health outcomes globally. However, vaccine coverage among children is unevenly distributed across settings and populations. The measurement of inequalities is essential for understanding gaps in vaccine coverage affecting certain sub-populations and [...] Read more.

Immunization through vaccines among children has contributed to improved childhood survival and health outcomes globally. However, vaccine coverage among children is unevenly distributed across settings and populations. The measurement of inequalities is essential for understanding gaps in vaccine coverage affecting certain sub-populations and monitoring progress towards achieving equity. Our study aimed to characterize the methods of reporting inequalities in childhood vaccine coverage, inclusive of the settings, data source types, analytical methods, and reporting modalities used to quantify and communicate inequality. We conducted a scoping review of publications in academic journals which included analyses of inequalities in vaccination among children. Literature searches were conducted in PubMed and Web of Science and included relevant articles published between 8 December 2013 and 7 December 2023. Overall, 242 publications were identified, including 204 assessing inequalities in a single country and 38 assessing inequalities across more than one country. We observed that analyses on inequalities in childhood vaccine coverage rely heavily on Demographic Health Survey (DHS) or Multiple Indicator Cluster Surveys (MICS) data (39.3%), and papers leveraging these data had increased in the last decade. Additionally, about half of the single-country studies were conducted in low- and middle-income countries. We found that few studies analyzed and reported inequalities using summary measures of health inequality and largely used the odds ratio resulting from logistic regression models for analyses. The most analyzed dimensions of inequality were economic status and maternal education, and the most common vaccine outcome indicator was full vaccination with the recommended vaccine schedule. However, the definition and construction of both dimensions of inequality and vaccine coverage measures varied across studies, and a variety of approaches were used to study inequalities in vaccine coverage across contexts. Overall, harmonizing methods for selecting and categorizing dimensions of inequalities as well as methods for analyzing and reporting inequalities can improve our ability to assess the magnitude and patterns of inequality in vaccine coverage and compare those inequalities across settings and time. Full article

(This article belongs to the Special Issue Inequality in Immunization 2024)

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18 pages, 11542 KB

Open AccessEditor’s ChoiceArticle

Gold Nanoparticle Virus-like Particles Presenting SARS-CoV-2 Spike Protein: Synthesis, Biophysical Properties and Immunogenicity in BALB/c Mice

by Vivian A. Salazar, Joan Comenge, Rosa Suárez-López, Judith A. Burger, Rogier W. Sanders, Neus G. Bastús, Carlos Jaime, Joan Joseph-Munne and Victor Puntes

Vaccines 2024, 12(8), 829; https://doi.org/10.3390/vaccines12080829 - 23 Jul 2024

Cited by 7 | Viewed by 4221

Abstract

Gold nanoparticles (AuNPs) decorated with antigens have recently emerged as promising tools for vaccine development due to their innate ability to provide stability to antigens and modulate immune responses. In this study, we have engineered deactivated virus-like particles (VLPs) by precisely functionalizing gold [...] Read more.

Gold nanoparticles (AuNPs) decorated with antigens have recently emerged as promising tools for vaccine development due to their innate ability to provide stability to antigens and modulate immune responses. In this study, we have engineered deactivated virus-like particles (VLPs) by precisely functionalizing gold cores with coronas comprising the full SARS-CoV-2 spike protein (S). Using BALB/c mice as a model, we investigated the immunogenicity of these S-AuNPs-VLPs. Our results demonstrate that S-AuNPs-VLPs consistently enhanced antigen-specific antibody responses compared to the S protein free in solution. This enhancement included higher binding antibody titers, higher neutralizing capacity of antibodies, and stronger T-cell responses. Compared to the mRNA COVID-19 vaccine, where the S protein is synthesized in situ, S-AuNPs-VLPs induced comparable binding and neutralizing antibody responses, but substantially superior T-cell responses. In conclusion, our study highlights the potential of conjugated AuNPs as an effective antigen-delivery system for protein-based vaccines targeting a broad spectrum of infectious diseases and other emergent viruses. Full article

(This article belongs to the Special Issue Virus-Like Particle Vaccine Development)

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14 pages, 538 KB

Open AccessEditor’s ChoiceReview

The Problem with Delaying Measles Elimination

by Natasha S. Crowcroft, Anna A. Minta, Shelly Bolotin, Tania Cernuschi, Archchun Ariyarajah, Sébastien Antoni, Mick N. Mulders, Anindya S. Bose and Patrick M. O’Connor

Vaccines 2024, 12(7), 813; https://doi.org/10.3390/vaccines12070813 - 22 Jul 2024

Cited by 11 | Viewed by 7074

Abstract

Measles is a highly infectious disease leading to high morbidity and mortality impacting people’s lives and economies across the globe. The measles vaccine saves more lives than any other vaccine in the Essential Programme of Immunization and is also the most cost-effective vaccine, [...] Read more.

Measles is a highly infectious disease leading to high morbidity and mortality impacting people’s lives and economies across the globe. The measles vaccine saves more lives than any other vaccine in the Essential Programme of Immunization and is also the most cost-effective vaccine, with an extremely high return on investment. This makes achieving measles elimination through vaccination a key child health intervention, particularly in low-income countries, where the overwhelming majority of measles deaths continue to occur. All countries and regions of the world have committed to achieving measles elimination, yet many have faced challenges securing political commitment at national and global levels and predictable, timely, and flexible support from global donors, and experienced setbacks during the COVID-19 pandemic. This has happened against a backdrop of stagnant measles vaccination coverage and declining enthusiasm for vertical programmes, culminating in a World Health Organization Strategic Advisory Group of Experts (WHO SAGE) review of the feasibility of measles eradication in 2019. Sustaining the elimination of measles long term is extremely difficult, and some countries have lost or nearly lost their measles elimination status in the face of ongoing importation of cases from neighbouring or closely connected countries in which elimination had been delayed. Thus, a widening equity gap in measles immunisation coverage creates challenges for all countries, not just those facing the greatest burden of measles morbidity and mortality. Delaying elimination of measles in some countries makes it cumulatively harder for all countries to succeed for three principal reasons: increased inequity in measles immunisation coverage makes outbreaks more likely to happen and to be larger; political will is very difficult to sustain; and immunity may wane to a point that transmission is re-established. New strategies are needed to support countries and regions in their vision for a world without measles, including ways to galvanise domestic, regional and global resources and ignite the political will that is essential to make the vision a reality. Full article

(This article belongs to the Special Issue A World without Measles and Rubella: Meeting the Regional Elimination Targets on the Path to Global Eradication)

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12 pages, 3426 KB

Open AccessEditor’s ChoiceArticle

Implementation of mRNA–Lipid Nanoparticle Technology in Atlantic Salmon (Salmo salar)

by Lars Ole Sti Dahl, Sjoerd Hak, Stine Braaen, Alicja Molska, Francesca Rodà, Jeremie Parot, Øystein Wessel, Johanna Hol Fosse, Håvard Bjørgen, Sven Even Borgos and Espen Rimstad

Vaccines 2024, 12(7), 788; https://doi.org/10.3390/vaccines12070788 - 18 Jul 2024

Cited by 7 | Viewed by 4528

Abstract

Background: This study was conducted to investigate whether mRNA vaccine technology could be adapted for the ectothermic vertebrate Atlantic salmon (Salmo salar). Lipid nanoparticle (LNP) technology has been developed and optimized for mRNA vaccines in mammals, stabilizing mRNA and facilitating its [...] Read more.

Background: This study was conducted to investigate whether mRNA vaccine technology could be adapted for the ectothermic vertebrate Atlantic salmon (Salmo salar). Lipid nanoparticle (LNP) technology has been developed and optimized for mRNA vaccines in mammals, stabilizing mRNA and facilitating its delivery into cells. However, its utility at the temperatures and specific biological environments present in ectotherms remains unclear. In addition, it is unknown if modified mRNA containing non-canonical nucleotides can correctly translate in salmonid cells. Methods: We used an mRNA transcript coding for enhanced green fluorescence protein, flanked by the untranslated regions of the hemagglutinin-esterase gene of the infectious salmon anemia virus, and a 120-base-long poly(A) tail. The mRNA was generated via in vitro transcription where uridine residues were replaced with N1-methyl-pseudouridines, and then encapsulated in LNPs. Results: When transfected into the salmonid cell line CHH-1, the mRNA-LNP construct induced expression of EGFP. Furthermore, when mRNA-LNPs were injected intramuscularly into salmon, in vivo protein expression was demonstrated via immunohistochemistry. EGFP was observed in cells infiltrating the spaces between muscle cells in a focal inflammatory response. Conclusion: The results indicate that N1-methyl-pseudouridine-modified mRNA encapsulated in LNPs can be used to express antigens of interest in salmonid fish. Full article

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

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38 pages, 776 KB

Open AccessEditor’s ChoiceReview

Transforming Aquaculture through Vaccination: A Review on Recent Developments and Milestones

by Iosif Tammas, Konstantina Bitchava and Athanasios I. Gelasakis

Vaccines 2024, 12(7), 732; https://doi.org/10.3390/vaccines12070732 - 1 Jul 2024

Cited by 49 | Viewed by 13041

Abstract

Aquaculture has rapidly emerged as one of the fastest growing industries, expanding both on global and on national fronts. With the ever-increasing demand for proteins with a high biological value, the aquaculture industry has established itself as one of the most efficient forms [...] Read more.

Aquaculture has rapidly emerged as one of the fastest growing industries, expanding both on global and on national fronts. With the ever-increasing demand for proteins with a high biological value, the aquaculture industry has established itself as one of the most efficient forms of animal production, proving to be a vital component of global food production by supplying nearly half of aquatic food products intended for human consumption. As in classic animal production, the prevention of diseases constitutes an enduring challenge associated with severe economic and environmental repercussions. Nevertheless, remarkable strides in the development of aquaculture vaccines have been recently witnessed, offering sustainable solutions to persistent health-related issues challenging resilient aquaculture production. These advancements are characterized by breakthroughs in increased species-specific precision, improved vaccine-delivery systems, and innovations in vaccine development, following the recent advent of nanotechnology, biotechnology, and artificial intelligence in the -omics era. The objective of this paper was to assess recent developments and milestones revolving around aquaculture vaccinology and provide an updated overview of strengths, weaknesses, opportunities, and threats of the sector, by incorporating and comparatively discussing various diffuse advances that span across a wide range of topics, including emerging vaccine technologies, innovative delivery methods, insights on novel adjuvants, and parasite vaccine development for the aquaculture sector. Full article

(This article belongs to the Special Issue Fish Disease Occurrence and Immune Prevention and Control)

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10 pages, 250 KB

Open AccessEditor’s ChoiceReview

Hepatitis E Vaccines Updates

by Christopher Hartley, Paul Wasuwanich, Trung Van and Wikrom Karnsakul

Vaccines 2024, 12(7), 722; https://doi.org/10.3390/vaccines12070722 - 28 Jun 2024

Cited by 7 | Viewed by 4785

Abstract

The development of a hepatitis E vaccine is imperative given its prevalence and the heightened risk it poses to specific populations. Hepatitis E virus infection, though often self-limiting, poses a significant threat to pregnant individuals and immunocompromised populations. This review delves into the [...] Read more.

The development of a hepatitis E vaccine is imperative given its prevalence and the heightened risk it poses to specific populations. Hepatitis E virus infection, though often self-limiting, poses a significant threat to pregnant individuals and immunocompromised populations. This review delves into the historical trajectory of hepatitis E vaccine development and explores its potential impact on at-risk populations. Historically, efforts to formulate an effective vaccine against hepatitis E have been underway to mitigate the severity of the disease, particularly in regions where the infection is commonplace. As a self-limiting disease, the necessity of a vaccine becomes more pronounced when considering vulnerable demographics. Pregnant individuals face heightened complications, with potential adverse outcomes for both mother and child. Similarly, immunocompromised individuals experience prolonged and severe manifestations of the infection, necessitating targeted preventive measures. This review aims to provide a comprehensive overview of the milestones in hepatitis E vaccine development. By examining the historical progression, we aim to underscore the critical need for a vaccine to safeguard not only the general population but also those at elevated risk. The elucidation of the vaccine’s journey will contribute valuable insights into its potential benefits, aiding in the formulation of informed public health strategies to combat hepatitis E effectively. Full article

(This article belongs to the Special Issue Vaccination and Treatments against Viral Hepatitis: Achievements, Challenges and Perspectives)

20 pages, 6664 KB

Open AccessEditor’s ChoiceArticle

Buccal Administration of a Zika Virus Vaccine Utilizing 3D-Printed Oral Dissolving Films in a Mouse Model

by Sarthak Shah, Parth Patel, Amarae Ferguson, Priyal Bagwe, Akanksha Kale, Emmanuel Adediran, Revanth Singh, Tanisha Arte, Dedeepya Pasupuleti, Mohammad N. Uddin and Martin D’Souza

Vaccines 2024, 12(7), 720; https://doi.org/10.3390/vaccines12070720 - 28 Jun 2024

Cited by 8 | Viewed by 3243

Abstract

Over the years, research regarding the Zika virus has been steadily increasing. Early immunization for ZIKV is a priority for preventing complications such as microencephaly and Guillain–Barré syndrome (GBS). Unlike traditional vaccination approaches, oral dissolving films (ODFs) or mucoadhesive film technology is an [...] Read more.

Over the years, research regarding the Zika virus has been steadily increasing. Early immunization for ZIKV is a priority for preventing complications such as microencephaly and Guillain–Barré syndrome (GBS). Unlike traditional vaccination approaches, oral dissolving films (ODFs) or mucoadhesive film technology is an emerging, exciting concept that can be used in the field of pharmaceuticals for vaccine design and formulation development. This attractive and novel method can help patients who suffer from dysphagia as a complication of a disease or syndrome. In this study, we investigated a microparticulate Zika vaccine administered via the buccal route with the help of thin films or oral dissolving films (ODFs) with a prime dose and two booster doses two weeks apart. In vitro, the ODFs displayed excellent physiochemical properties, indicating that the films were good carriers for vaccine microparticles and biocompatible with the buccal mucosa. In vivo results revealed robust humoral (IgG, subtypes IgG1 and IgG2a) and T-cell responses (CD4+/CD8+) for ZIKV-specific immunity. Both the Zika MP vaccine and the adjuvanted Zika MP vaccine affected memory (CD45R/CD27) and intracellular cytokine (TNF-α and IL-6) expression. In this study, ZIKV vaccination via the buccal route with the aid of ODFs demonstrated great promise for the development of pain-free vaccines for infectious diseases. Full article

(This article belongs to the Special Issue Advances in the Use of Nanoparticles for Vaccine Platform Development)

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20 pages, 1439 KB

Open AccessEditor’s ChoiceArticle

Progress and Challenges in Measles and Rubella Elimination in the WHO European Region

by Mark Muscat, Myriam Ben Mamou, Catharina Reynen-de Kat, Dragan Jankovic, José Hagan, Simarjit Singh and Siddhartha Sankar Datta

Vaccines 2024, 12(6), 696; https://doi.org/10.3390/vaccines12060696 - 20 Jun 2024

Cited by 14 | Viewed by 11357

Abstract

The elimination of both measles and rubella remains a priority for all 53 Member States of the World Health Organization (WHO) European Region. To provide an update on the epidemiological status of measles and rubella in the Region, we reviewed surveillance data on [...] Read more.

The elimination of both measles and rubella remains a priority for all 53 Member States of the World Health Organization (WHO) European Region. To provide an update on the epidemiological status of measles and rubella in the Region, we reviewed surveillance data on both diseases for 2023 submitted monthly by national surveillance institutions. We analyzed the cases of measles and rubella for 2023 by age group, case classification, vaccination, hospitalization, and importation status and report on measles-related deaths. In 2023, 60,860 measles cases, including 13 fatal cases, were reported in 41 countries. Most cases (95%; n = 57,584) were reported by six countries: Azerbaijan, Kazakhstan, Kyrgyzstan, Romania, the Russian Federation, and Türkiye. Of the 60,848 cases with data on age, 19,137 (31%) were 1–4 years old and 12,838 (21%) were 5–9 years old. A total of 10,412 (17%) were 20 years and older. The genotypes identified in the Region were largely dominated by D8 variants (n = 1357) and the remainder were B3 variants (n = 221). In 2023, 345 rubella cases were reported by 17 countries, mostly from Poland, Kyrgyzstan, Tajikistan, Türkiye, and Ukraine. A total of 262 cases (76%) were classified as clinically compatible and 79 (23%) were laboratory-confirmed. To achieve the elimination of measles and rubella in the Region, political commitment needs to be revived to enable urgent efforts to increase vaccination coverage, improve surveillance and outbreak preparedness, and respond immediately to outbreaks. Full article

(This article belongs to the Special Issue A World without Measles and Rubella: Meeting the Regional Elimination Targets on the Path to Global Eradication)

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15 pages, 2848 KB

Open AccessEditor’s ChoiceArticle

SARS-CoV-2-Specific Immune Cytokine Profiles to mRNA, Viral Vector and Protein-Based Vaccines in Patients with Multiple Sclerosis: Beyond Interferon Gamma

by Georges Katoul Al Rahbani, Christina Woopen, Marie Dunsche, Undine Proschmann, Tjalf Ziemssen and Katja Akgün

Vaccines 2024, 12(6), 684; https://doi.org/10.3390/vaccines12060684 - 19 Jun 2024

Cited by 5 | Viewed by 5499

Abstract

Disease-modifying therapies (DMTs) impact the cellular immune response to severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccines in patients with multiple sclerosis (pwMS). In this study, we aim to elucidate the characteristics of the involved antigen-specific T cells via the measurement of [...] Read more.

Disease-modifying therapies (DMTs) impact the cellular immune response to severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccines in patients with multiple sclerosis (pwMS). In this study, we aim to elucidate the characteristics of the involved antigen-specific T cells via the measurement of broad cytokine profiles in pwMS on various DMTs. We examined SARS-CoV-2-specific T cell responses in whole blood cultures characterized by the release of interleukin (IL)-2, IL-4, IL-5, IL-10, IL-13, IL-17A, interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α), as well as antibodies (AB) targeting the SARS-CoV-2 spike protein in pwMS following either two or three doses of mRNA or viral vector vaccines (VVV). For mRNA vaccination non-responders, the NVX-CoV2373 protein-based vaccine was administered, and immune responses were evaluated. Our findings indicate that immune responses to SARS-CoV-2 vaccines in pwMS are skewed towards a Th1 phenotype, characterized by IL-2 and IFN-γ. Additionally, a Th2 response characterized by IL-5, and to a lesser extent IL-4, IL-10, and IL-13, is observed. Therefore, the measurement of IL-2 and IL-5 levels could complement traditional IFN-γ assays to more comprehensively characterize the cellular responses to SARS-CoV-2 vaccines. Our results provide a comprehensive cytokine profile for pwMS receiving different DMTs and offer valuable insights for designing vaccination strategies in this patient population. Full article

(This article belongs to the Special Issue Interferon Responses after Vaccine Administration)

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32 pages, 2118 KB

Open AccessEditor’s ChoiceReview

An Overview of the Strategies to Boost SARS-CoV-2-Specific Immunity in People with Inborn Errors of Immunity

by Emma Chang-Rabley, Menno C. van Zelm, Emily E. Ricotta and Emily S. J. Edwards

Vaccines 2024, 12(6), 675; https://doi.org/10.3390/vaccines12060675 - 18 Jun 2024

Cited by 7 | Viewed by 4220

Abstract

The SARS-CoV-2 pandemic has heightened concerns about immunological protection, especially for individuals with inborn errors of immunity (IEI). While COVID-19 vaccines elicit strong immune responses in healthy individuals, their effectiveness in IEI patients remains unclear, particularly against new viral variants and vaccine formulations. [...] Read more.

The SARS-CoV-2 pandemic has heightened concerns about immunological protection, especially for individuals with inborn errors of immunity (IEI). While COVID-19 vaccines elicit strong immune responses in healthy individuals, their effectiveness in IEI patients remains unclear, particularly against new viral variants and vaccine formulations. This uncertainty has led to anxiety, prolonged self-isolation, and repeated vaccinations with uncertain benefits among IEI patients. Despite some level of immune response from vaccination, the definition of protective immunity in IEI individuals is still unknown. Given their susceptibility to severe COVID-19, strategies such as immunoglobulin replacement therapy (IgRT) and monoclonal antibodies have been employed to provide passive immunity, and protection against both current and emerging variants. This review examines the efficacy of COVID-19 vaccines and antibody-based therapies in IEI patients, their capacity to recognize viral variants, and the necessary advances required for the ongoing protection of people with IEIs. Full article

(This article belongs to the Special Issue Influence of Natural and/or Vaccine Immunity on the Dynamics of SARS-CoV-2)

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17 pages, 3627 KB

Open AccessEditor’s ChoiceReview

Exploring the Potential of Natural Killer Cell-Based Immunotherapy in Targeting High-Grade Serous Ovarian Carcinomas

by Kawaljit Kaur, Jashan Sanghu, Sanaz Memarzadeh and Anahid Jewett

Vaccines 2024, 12(6), 677; https://doi.org/10.3390/vaccines12060677 - 18 Jun 2024

Cited by 7 | Viewed by 9063

Abstract

High-grade serous ovarian cancers (HGSOCs) likely consist of poorly differentiated stem-like cells (PDSLCs) and differentiated tumor cells. Conventional therapeutics are incapable of completely eradicating PDSLCs, contributing to disease progression and tumor relapse. Primary NK cells are known to effectively lyse PDSLCs, but they [...] Read more.

High-grade serous ovarian cancers (HGSOCs) likely consist of poorly differentiated stem-like cells (PDSLCs) and differentiated tumor cells. Conventional therapeutics are incapable of completely eradicating PDSLCs, contributing to disease progression and tumor relapse. Primary NK cells are known to effectively lyse PDSLCs, but they exhibit low or minimal cytotoxic potential against well-differentiated tumors. We have introduced and discussed the characteristics of super-charged NK (sNK) cells in this review. sNK cells, in comparison to primary NK cells, exhibit a significantly higher capability for the direct killing of both PDSLCs and well-differentiated tumors. In addition, sNK cells secrete significantly higher levels of cytokines, especially those known to induce the differentiation of tumors. In addition, we propose that a combination of sNK and chemotherapy could be one of the most effective strategies to eliminate the heterogeneous population of ovarian tumors; sNK cells can lyse both PDSLCs and well-differentiated tumors, induce the differentiation of PDSLCs, and could be used in combination with chemotherapy to target both well-differentiated and NK-induced differentiated tumors. Full article

(This article belongs to the Section Vaccination Against Cancer and Chronic Diseases)

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15 pages, 5690 KB

Open AccessEditor’s ChoiceArticle

mRNA Vaccine for Alzheimer’s Disease: Pilot Study

by Armine Hovakimyan, Garri Chilingaryan, Olga King, Joia Kai Capocchi, Jean Paul Chadarevian, Hayk Davtyan, Roman Kniazev, Michael G. Agadjanyan and Anahit Ghochikyan

Vaccines 2024, 12(6), 659; https://doi.org/10.3390/vaccines12060659 - 14 Jun 2024

Cited by 7 | Viewed by 9931

Abstract

The escalating global healthcare challenge posed by Alzheimer’s Disease (AD) and compounded by the lack of effective treatments emphasizes the urgent need for innovative approaches to combat this devastating disease. Currently, passive and active immunotherapies remain the most promising strategy for AD. FDA-approved [...] Read more.

The escalating global healthcare challenge posed by Alzheimer’s Disease (AD) and compounded by the lack of effective treatments emphasizes the urgent need for innovative approaches to combat this devastating disease. Currently, passive and active immunotherapies remain the most promising strategy for AD. FDA-approved lecanemab significantly reduces Aβ aggregates from the brains of early AD patients administered biweekly with this humanized monoclonal antibody. Although the clinical benefits noted in these trials have been modest, researchers have emphasized the importance of preventive immunotherapy. Importantly, data from immunotherapy studies have shown that antibody concentrations in the periphery of vaccinated people should be sufficient for targeting Aβ in the CNS. To generate relatively high concentrations of antibodies in vaccinated people at risk of AD, we generated a universal vaccine platform, MultiTEP, and, based on it, developed a DNA vaccine, AV-1959D, targeting pathological Aβ, completed IND enabling studies, and initiated a Phase I clinical trial with early AD volunteers. Our current pilot study combined our advanced MultiTEP technology with a novel mRNA approach to develop an mRNA vaccine encapsulated in lipid-based nanoparticles (LNPs), AV-1959LR. Here, we report our initial findings on the immunogenicity of 1959LR in mice and non-human primates, comparing it with the immunogenicity of its DNA counterpart, AV-1959D. Full article

(This article belongs to the Special Issue Feature Papers of DNA and mRNA Vaccines)

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