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Comparative analysis of the impact of 40 adenovirus types on dendritic cell activation and CD8(+) T cell proliferation capacity for the identification of favorable immunization vector candidates

For the development of new adenovirus (AdV)-based vectors, it is important to understand differences in immunogenicity. In a side-by-side in vitro analysis, we evaluated the effect of 40 AdV types covering human AdV (HAdV) species A through G on the expression of 11 activation markers and the secret...

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Autores principales: Wang, Xiaoyan, Hetzel, Mario, Zhang, Wenli, Ehrhardt, Anja, Bayer, Wibke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10616870/
https://www.ncbi.nlm.nih.gov/pubmed/37915567
http://dx.doi.org/10.3389/fimmu.2023.1286622
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author Wang, Xiaoyan
Hetzel, Mario
Zhang, Wenli
Ehrhardt, Anja
Bayer, Wibke
author_facet Wang, Xiaoyan
Hetzel, Mario
Zhang, Wenli
Ehrhardt, Anja
Bayer, Wibke
author_sort Wang, Xiaoyan
collection PubMed
description For the development of new adenovirus (AdV)-based vectors, it is important to understand differences in immunogenicity. In a side-by-side in vitro analysis, we evaluated the effect of 40 AdV types covering human AdV (HAdV) species A through G on the expression of 11 activation markers and the secretion of 12 cytokines by AdV-transduced dendritic cells, and the effect on CD8(+) T cell proliferation capacity. We found that the expression of activation markers and cytokines differed widely between the different HAdV types, and many types were able to significantly impair the proliferation capacity of CD8(+) T cells. Univariate and multivariate regression analyses suggested an important role of type I interferons in mediating this suppression of CD8(+) T cells, which we confirmed experimentally in a proliferation assay using a type I interferon receptor blocking antibody. Using Bayesian statistics, we calculated a prediction model that suggests HAdV types HAdV-C1, -D8, -B7, -F41, -D33, -C2, -A31, -B3 and -D65 as the most favorable candidates for vaccine vector development.
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spelling pubmed-106168702023-11-01 Comparative analysis of the impact of 40 adenovirus types on dendritic cell activation and CD8(+) T cell proliferation capacity for the identification of favorable immunization vector candidates Wang, Xiaoyan Hetzel, Mario Zhang, Wenli Ehrhardt, Anja Bayer, Wibke Front Immunol Immunology For the development of new adenovirus (AdV)-based vectors, it is important to understand differences in immunogenicity. In a side-by-side in vitro analysis, we evaluated the effect of 40 AdV types covering human AdV (HAdV) species A through G on the expression of 11 activation markers and the secretion of 12 cytokines by AdV-transduced dendritic cells, and the effect on CD8(+) T cell proliferation capacity. We found that the expression of activation markers and cytokines differed widely between the different HAdV types, and many types were able to significantly impair the proliferation capacity of CD8(+) T cells. Univariate and multivariate regression analyses suggested an important role of type I interferons in mediating this suppression of CD8(+) T cells, which we confirmed experimentally in a proliferation assay using a type I interferon receptor blocking antibody. Using Bayesian statistics, we calculated a prediction model that suggests HAdV types HAdV-C1, -D8, -B7, -F41, -D33, -C2, -A31, -B3 and -D65 as the most favorable candidates for vaccine vector development. Frontiers Media S.A. 2023-10-17 /pmc/articles/PMC10616870/ /pubmed/37915567 http://dx.doi.org/10.3389/fimmu.2023.1286622 Text en Copyright © 2023 Wang, Hetzel, Zhang, Ehrhardt and Bayer https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Wang, Xiaoyan
Hetzel, Mario
Zhang, Wenli
Ehrhardt, Anja
Bayer, Wibke
Comparative analysis of the impact of 40 adenovirus types on dendritic cell activation and CD8(+) T cell proliferation capacity for the identification of favorable immunization vector candidates
title Comparative analysis of the impact of 40 adenovirus types on dendritic cell activation and CD8(+) T cell proliferation capacity for the identification of favorable immunization vector candidates
title_full Comparative analysis of the impact of 40 adenovirus types on dendritic cell activation and CD8(+) T cell proliferation capacity for the identification of favorable immunization vector candidates
title_fullStr Comparative analysis of the impact of 40 adenovirus types on dendritic cell activation and CD8(+) T cell proliferation capacity for the identification of favorable immunization vector candidates
title_full_unstemmed Comparative analysis of the impact of 40 adenovirus types on dendritic cell activation and CD8(+) T cell proliferation capacity for the identification of favorable immunization vector candidates
title_short Comparative analysis of the impact of 40 adenovirus types on dendritic cell activation and CD8(+) T cell proliferation capacity for the identification of favorable immunization vector candidates
title_sort comparative analysis of the impact of 40 adenovirus types on dendritic cell activation and cd8(+) t cell proliferation capacity for the identification of favorable immunization vector candidates
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10616870/
https://www.ncbi.nlm.nih.gov/pubmed/37915567
http://dx.doi.org/10.3389/fimmu.2023.1286622
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