Antiviral T and B Cell Immunity

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Innate and Adaptive Immunity in Vaccination".

Deadline for manuscript submissions: 15 July 2025 | Viewed by 7932

Special Issue Editors


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Guest Editor
Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital, Lausanne, Switzerland
Interests: tissue immunology; imaging; HIV; SIV; vaccines

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Guest Editor
Department of Pathology & Laboratory Medicine, Emory School of Medicine, Emory University, Atlanta, GA 30322, USA
Interests: tissue immunology; imaging; HIV; SIV; vaccines

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Guest Editor
Emory Vaccine Center, Pathology Advanced Translational Research Unit (PATRU), Department of Pathology, Winship Cancer Institute, Emory University, School of Medicine, Atlanta, GA 30322, USA
Interests: HIV; inflammation; HIV reservoir; IL-10; follicular helper cells; antivirals; restriction factors; neuro-inflammation
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Special Issue Information

Dear Colleagues,

  1. The invasion of the human body by a pathogen (or only virus) triggers a cascade of immune reactions, ultimately leading to the development of adaptive specific immune responses aiming to achieve pathogen restriction and elimination. The generation of antigen-specific CD4/CD8 and B cell responses represent the two branches that the immune system utilizes to counteract the invasion of a virus. Although the development and function of the immune cell subsets involved in this process have been extensively studied in appropriate animal models, the corresponding immune reactions, programming of relevant cells, and their interaction with the tissue microenvironment where these reactions are taking place are less understood in human health and disease. Animal models validate but do not extrapolate directly to humans. The lack of relevant human material is a major restriction factor for the comprehensive study of such immune reactivity. Another major restriction factor is the lack of longitudinal samples even from blood; therefore, the time-dependent development of such responses is challenging. The comparative analysis of immune responses across different viral diseases and compared to other chronic inflammatory diseases like cancer could provide valuable information for the development and adaptiveness of antiviral responses in different inflammatory environments.
  2. The aim of this Special Issue is to present the latest developments regarding the dynamics of human antiviral immune responses and how this knowledge could fuel the further development of novel vaccine strategies. The comprehensive understanding of relevant immune cell phenotypes and their function, molecular programming, and spatial positioning at the tissue level will significantly improve our knowledge for their development and will potentially provide novel molecules/pathways that could be used for the discovery of novel strategies aiming towards in vivo generation/manipulation and the elimination of viruses like HIV.
  3. Suggested themes and article types for submissions.

In this Special Issue, original research articles and reviews are welcome. Research areas may include, but not limited to, the following:

  1. Vaccine-induced antiviral responses: phenotypes, molecular programming, tissue dynamics.
  2. Natural infection-induced antiviral responses, especially ones focused on secondary lymphoid organs and how that could inform vaccine development.
  3. Novel technologies for the investigation of antiviral responses/immune dynamics, with emphasis on their spatial positioning.
  4. Studies on relevant animal models, NHP, and humanized mice.
  5. Comparative studies of immune dynamics between different diseases.

We look forward to receiving your contributions.

Dr. Constantinos Petrovas
Dr. Ashish Arunkumar Sharma
Dr. Susan Pereira Ribeiro
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Vaccines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • virus
  • adaptive immunity
  • pathogenesis
  • vaccines

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Published Papers (5 papers)

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Research

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12 pages, 1598 KiB  
Article
The Identification of Dual T-Cell and B-Cell Epitopes Within Viral Proteins Utilizing a Comprehensive Peptide Array Approach
by Binghang Liu, Muqun Bai, Fei Zheng, Mingchen Yan, Enen Huang, Jie Wen, Yingrui Li and Jun Wang
Vaccines 2025, 13(3), 239; https://doi.org/10.3390/vaccines13030239 - 26 Feb 2025
Viewed by 631
Abstract
Background/Objectives: The development of vaccines that elicit both T-cell and B-cell responses is crucial for effective immunity against pathogens. This study introduces a novel approach to identify precise epitope peptides within viral proteins that can stimulate both arms of the adaptive immune response, [...] Read more.
Background/Objectives: The development of vaccines that elicit both T-cell and B-cell responses is crucial for effective immunity against pathogens. This study introduces a novel approach to identify precise epitope peptides within viral proteins that can stimulate both arms of the adaptive immune response, using Porcine Parvovirus (PPV) as a model. Methods: Mice were infected with PPV, and a peptide array was utilized to detect IgG signals in their sera. This approach facilitated the assessment of the immunogenicity of the PPV proteome, leading to the identification of 14 potential epitope candidates. These candidates were then used to immunize additional mice, and their ability to induce T-cell and B-cell responses was evaluated. Results: The immunization experiments identified an optimal peptide, P6, which robustly activated both T cells and B cells. Further analysis of the sub-regions of this peptide confirmed P6 as the most potent inducer of immune responses. The anticipated epitope was detected in mice immunized with P6, highlighting the efficacy of our method in identifying epitopes that engage both T cells and B cells. Conclusions: This study presents a novel strategy for the identification of dual T-cell and B-cell epitopes by directly evaluating the immunoreactivity of antibodies in serum. This finding holds significant promise for the advancement of epitope-based vaccines. Full article
(This article belongs to the Special Issue Antiviral T and B Cell Immunity)
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30 pages, 5323 KiB  
Article
B and T Cell Bi-Cistronic Multiepitopic Vaccine Induces Broad Immunogenicity and Provides Protection Against SARS-CoV-2
by Beatriz Perdiguero, Enrique Álvarez, Laura Marcos-Villar, Laura Sin, María López-Bravo, José Ramón Valverde, Carlos Óscar S. Sorzano, Michela Falqui, Rocío Coloma, Mariano Esteban, Susana Guerra and Carmen Elena Gómez
Vaccines 2024, 12(11), 1213; https://doi.org/10.3390/vaccines12111213 - 25 Oct 2024
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Abstract
Background: The COVID-19 pandemic, caused by SARS-CoV-2, has highlighted the need for vaccines targeting both neutralizing antibodies (NAbs) and long-lasting cross-reactive T cells covering multiple viral proteins to provide broad and durable protection against emerging variants. Methods: To address this, here we developed [...] Read more.
Background: The COVID-19 pandemic, caused by SARS-CoV-2, has highlighted the need for vaccines targeting both neutralizing antibodies (NAbs) and long-lasting cross-reactive T cells covering multiple viral proteins to provide broad and durable protection against emerging variants. Methods: To address this, here we developed two vaccine candidates, namely (i) DNA-CoV2-TMEP, expressing the multiepitopic CoV2-TMEP protein containing immunodominant and conserved T cell regions from SARS-CoV-2 structural proteins, and (ii) MVA-CoV2-B2AT, encoding a bi-cistronic multiepitopic construct that combines conserved B and T cell overlapping regions from SARS-CoV-2 structural proteins. Results: Both candidates were assessed in vitro and in vivo demonstrating their ability to induce robust immune responses. In C57BL/6 mice, DNA-CoV2-TMEP enhanced the recruitment of innate immune cells and stimulated SARS-CoV-2-specific polyfunctional T cells targeting multiple viral proteins. MVA-CoV2-B2AT elicited NAbs against various SARS-CoV-2 variants of concern (VoCs) and reduced viral replication and viral yields against the Beta variant in susceptible K18-hACE2 mice. The combination of MVA-CoV2-B2AT with a mutated ISG15 form as an adjuvant further increased the magnitude, breadth and polyfunctional profile of the response. Conclusion: These findings underscore the potential of these multiepitopic proteins when expressed from DNA or MVA vectors to provide protection against SARS-CoV-2 and its variants, supporting their further development as next-generation COVID-19 vaccines. Full article
(This article belongs to the Special Issue Antiviral T and B Cell Immunity)
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18 pages, 5357 KiB  
Article
Follicular Immune Landscaping Reveals a Distinct Profile of FOXP3hiCD4hi T Cells in Treated Compared to Untreated HIV
by Spiros Georgakis, Michail Orfanakis, Cloe Brenna, Simon Burgermeister, Perla M. Del Rio Estrada, Mauricio González-Navarro, Fernanda Torres-Ruiz, Gustavo Reyes-Terán, Santiago Avila-Rios, Yara Andrea Luna-Villalobos, Oliver Y. Chén, Giuseppe Pantaleo, Richard A. Koup and Constantinos Petrovas
Vaccines 2024, 12(8), 912; https://doi.org/10.3390/vaccines12080912 - 12 Aug 2024
Cited by 1 | Viewed by 1333
Abstract
Follicular helper CD4hi T cells (TFH) are a major cellular pool for the maintenance of the HIV reservoir. Therefore, the delineation of the follicular (F)/germinal center (GC) immune landscape will significantly advance our understanding of HIV pathogenesis. We have applied [...] Read more.
Follicular helper CD4hi T cells (TFH) are a major cellular pool for the maintenance of the HIV reservoir. Therefore, the delineation of the follicular (F)/germinal center (GC) immune landscape will significantly advance our understanding of HIV pathogenesis. We have applied multiplex confocal imaging, in combination with the relevant computational tools, to investigate F/GC in situ immune dynamics in viremic (vir-HIV), antiretroviral-treated (cART HIV) People Living With HIV (PLWH) and compare them to reactive, non-infected controls. Lymph nodes (LNs) from viremic and cART PLWH could be further grouped based on their TFH cell densities in high-TFH and low-TFH subgroups. These subgroups were also characterized by different in situ distributions of PD1hi TFH cells. Furthermore, a significant accumulation of follicular FOXP3hiCD4hi T cells, which were characterized by a low scattering in situ distribution profile and strongly correlated with the cell density of CD8hi T cells, was found in the cART-HIV low-TFH group. An inverse correlation between plasma viral load and LN GrzBhiCD8hi T and CD16hiCD15lo cells was found. Our data reveal the complex GC immune landscaping in HIV infection and suggest that follicular FOXP3hiCD4hi T cells could be negative regulators of TFH cell prevalence in cART-HIV. Full article
(This article belongs to the Special Issue Antiviral T and B Cell Immunity)
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17 pages, 2466 KiB  
Article
Soluble Plasma Proteins of Tumor Necrosis Factor and Immunoglobulin Superfamilies Reveal New Insights into Immune Regulation in People with HIV and Opioid Use Disorder
by Priya P. Ghanta, Christine M. Dang, C. Mindy Nelson, Daniel J. Feaster, David W. Forrest, Hansel Tookes, Rajendra N. Pahwa, Suresh Pallikkuth and Savita G. Pahwa
Vaccines 2024, 12(5), 520; https://doi.org/10.3390/vaccines12050520 - 9 May 2024
Viewed by 2063
Abstract
People with HIV (PWH) frequently suffer from Opioid (OP) Use Disorder (OUD). In an investigation of the impact of OUD on underlying immune dysfunction in PWH, we previously reported that OP use exacerbates inflammation in virally controlled PWH followed in the Infectious Diseases [...] Read more.
People with HIV (PWH) frequently suffer from Opioid (OP) Use Disorder (OUD). In an investigation of the impact of OUD on underlying immune dysfunction in PWH, we previously reported that OP use exacerbates inflammation in virally controlled PWH followed in the Infectious Diseases Elimination Act (IDEA) Syringe Services Program (SSP). Unexpectedly, Flu vaccination-induced antibody responses in groups with OUD were superior to PWH without OUD. Here, we investigated the profile of 48 plasma biomarkers comprised of TNF and Ig superfamily (SF) molecules known to impact interactions between T and B cells in 209 participants divided into four groups: (1) HIV+OP+, (2) HIV−OP+, (3) HIV+OP−, and (4) HIV−OP−. The differential expression of the top eight molecules ranked by median values in individual Groups 1–3 in comparison to Group 4 was highly significant. Both OP+ groups 1 and 2 had higher co-stimulatory TNF SF molecules, including 4-1BB, OX-40, CD40, CD30, and 4-1BBL, which were found to positively correlate with Flu Ab titers. In contrast, HIV+OP− exhibited a profile dominant in Ig SF molecules, including PDL-2, CTLA-4, and Perforin, with PDL-2 showing a negative correlation with Flu vaccine titers. These findings are relevant to vaccine development in the fields of HIV and OUD. Full article
(This article belongs to the Special Issue Antiviral T and B Cell Immunity)
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Review

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16 pages, 1414 KiB  
Review
T Cell Responses during Human Immunodeficiency Virus/Mycobacterium tuberculosis Coinfection
by José Alejandro Bohórquez, Chinnaswamy Jagannath, Huanbin Xu, Xiaolei Wang and Guohua Yi
Vaccines 2024, 12(8), 901; https://doi.org/10.3390/vaccines12080901 - 9 Aug 2024
Cited by 1 | Viewed by 2090
Abstract
Coinfection with Mycobacterium tuberculosis (Mtb) and the human immunodeficiency virus (HIV) is a significant public health concern. Individuals infected with Mtb who acquire HIV are approximately 16 times more likely to develop active tuberculosis. T cells play an important role as [...] Read more.
Coinfection with Mycobacterium tuberculosis (Mtb) and the human immunodeficiency virus (HIV) is a significant public health concern. Individuals infected with Mtb who acquire HIV are approximately 16 times more likely to develop active tuberculosis. T cells play an important role as both targets for HIV infection and mediators of the immune response against both pathogens. This review aims to synthesize the current literature and provide insights into the effects of HIV/Mtb coinfection on T cell populations and their contributions to immunity. Evidence from multiple in vitro and in vivo studies demonstrates that T helper responses are severely compromised during coinfection, leading to impaired cytotoxic responses. Moreover, HIV’s targeting of Mtb-specific cells, including those within granulomas, offers an explanation for the severe progression of the disease. Herein, we discuss the patterns of differentiation, exhaustion, and transcriptomic changes in T cells during coinfection, as well as the metabolic adaptations that are necessary for T cell maintenance and functionality. This review highlights the interconnectedness of the immune response and the pathogenesis of HIV/Mtb coinfection. Full article
(This article belongs to the Special Issue Antiviral T and B Cell Immunity)
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