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Sequestration of Late Antigens Within Viral Factories Impairs MVA Vector-Induced Protective Memory CTL Responses

Cytotoxic CD8+ T cell (CTL) responses play an essential role in antiviral immunity. Here, we focused on the activation of CTL which recognize epitopes derived from viral or recombinant antigens with either early or late expression kinetics after infection with Modified Vaccinia Virus Ankara (MVA). L...

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Autores principales: Tao, Sha, Tao, Ronny, Busch, Dirk H., Widera, Marek, Schaal, Heiner, Drexler, Ingo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904312/
https://www.ncbi.nlm.nih.gov/pubmed/31867011
http://dx.doi.org/10.3389/fimmu.2019.02850
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author Tao, Sha
Tao, Ronny
Busch, Dirk H.
Widera, Marek
Schaal, Heiner
Drexler, Ingo
author_facet Tao, Sha
Tao, Ronny
Busch, Dirk H.
Widera, Marek
Schaal, Heiner
Drexler, Ingo
author_sort Tao, Sha
collection PubMed
description Cytotoxic CD8+ T cell (CTL) responses play an essential role in antiviral immunity. Here, we focused on the activation of CTL which recognize epitopes derived from viral or recombinant antigens with either early or late expression kinetics after infection with Modified Vaccinia Virus Ankara (MVA). Late antigens but not early antigens failed to efficiently stimulate murine CTL lines in vitro and were unable to activate and expand protective memory T cell responses in mice in vivo. The reduced or absent presentation of late antigens was not due to impaired antigen presentation or delayed protein synthesis, but was caused by sequestration of late antigens within viral factories (VFs). Additionally, the trapping of late antigens in VFs conflicts with antigen processing and presentation as proteasomal activity was strongly reduced or absent in VFs, suggesting inefficient antigen degradation. This study gives for the first time a mechanistic explanation for the weak immunogenicity of late viral antigens for memory CTL activation. Since MVA is preferentially used as a boost vector in heterologous prime/boost vaccinations, this is an important information for future vaccine design.
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spelling pubmed-69043122019-12-20 Sequestration of Late Antigens Within Viral Factories Impairs MVA Vector-Induced Protective Memory CTL Responses Tao, Sha Tao, Ronny Busch, Dirk H. Widera, Marek Schaal, Heiner Drexler, Ingo Front Immunol Immunology Cytotoxic CD8+ T cell (CTL) responses play an essential role in antiviral immunity. Here, we focused on the activation of CTL which recognize epitopes derived from viral or recombinant antigens with either early or late expression kinetics after infection with Modified Vaccinia Virus Ankara (MVA). Late antigens but not early antigens failed to efficiently stimulate murine CTL lines in vitro and were unable to activate and expand protective memory T cell responses in mice in vivo. The reduced or absent presentation of late antigens was not due to impaired antigen presentation or delayed protein synthesis, but was caused by sequestration of late antigens within viral factories (VFs). Additionally, the trapping of late antigens in VFs conflicts with antigen processing and presentation as proteasomal activity was strongly reduced or absent in VFs, suggesting inefficient antigen degradation. This study gives for the first time a mechanistic explanation for the weak immunogenicity of late viral antigens for memory CTL activation. Since MVA is preferentially used as a boost vector in heterologous prime/boost vaccinations, this is an important information for future vaccine design. Frontiers Media S.A. 2019-12-04 /pmc/articles/PMC6904312/ /pubmed/31867011 http://dx.doi.org/10.3389/fimmu.2019.02850 Text en Copyright © 2019 Tao, Tao, Busch, Widera, Schaal and Drexler. http://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
Tao, Sha
Tao, Ronny
Busch, Dirk H.
Widera, Marek
Schaal, Heiner
Drexler, Ingo
Sequestration of Late Antigens Within Viral Factories Impairs MVA Vector-Induced Protective Memory CTL Responses
title Sequestration of Late Antigens Within Viral Factories Impairs MVA Vector-Induced Protective Memory CTL Responses
title_full Sequestration of Late Antigens Within Viral Factories Impairs MVA Vector-Induced Protective Memory CTL Responses
title_fullStr Sequestration of Late Antigens Within Viral Factories Impairs MVA Vector-Induced Protective Memory CTL Responses
title_full_unstemmed Sequestration of Late Antigens Within Viral Factories Impairs MVA Vector-Induced Protective Memory CTL Responses
title_short Sequestration of Late Antigens Within Viral Factories Impairs MVA Vector-Induced Protective Memory CTL Responses
title_sort sequestration of late antigens within viral factories impairs mva vector-induced protective memory ctl responses
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904312/
https://www.ncbi.nlm.nih.gov/pubmed/31867011
http://dx.doi.org/10.3389/fimmu.2019.02850
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