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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doaj-502d914d24604e97a2400f82082696192020-11-25T02:08:51ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-12-011010.3389/fimmu.2019.02850500216Sequestration of Late Antigens Within Viral Factories Impairs MVA Vector-Induced Protective Memory CTL ResponsesSha Tao0Ronny Tao1Dirk H. Busch2Marek Widera3Heiner Schaal4Ingo Drexler5Institute for Virology, Düsseldorf University Hospital, Heinrich-Heine-University, Düsseldorf, GermanyInstitute for Virology, Düsseldorf University Hospital, Heinrich-Heine-University, Düsseldorf, GermanyInstitute of Microbiology, Immunology and Hygiene, Technical University Munich, Munich, GermanyInstitute for Virology, Düsseldorf University Hospital, Heinrich-Heine-University, Düsseldorf, GermanyInstitute for Virology, Düsseldorf University Hospital, Heinrich-Heine-University, Düsseldorf, GermanyInstitute for Virology, Düsseldorf University Hospital, Heinrich-Heine-University, Düsseldorf, GermanyCytotoxic 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.https://www.frontiersin.org/article/10.3389/fimmu.2019.02850/fullCTLantigen presentationModified Vaccinia Virus Ankara (MVA)memory T cell activationviral vector vaccineviral immunology |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sha Tao Ronny Tao Dirk H. Busch Marek Widera Heiner Schaal Ingo Drexler |
spellingShingle |
Sha Tao Ronny Tao Dirk H. Busch Marek Widera Heiner Schaal Ingo Drexler Sequestration of Late Antigens Within Viral Factories Impairs MVA Vector-Induced Protective Memory CTL Responses Frontiers in Immunology CTL antigen presentation Modified Vaccinia Virus Ankara (MVA) memory T cell activation viral vector vaccine viral immunology |
author_facet |
Sha Tao Ronny Tao Dirk H. Busch Marek Widera Heiner Schaal Ingo Drexler |
author_sort |
Sha Tao |
title |
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_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_sort |
sequestration of late antigens within viral factories impairs mva vector-induced protective memory ctl responses |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2019-12-01 |
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. |
topic |
CTL antigen presentation Modified Vaccinia Virus Ankara (MVA) memory T cell activation viral vector vaccine viral immunology |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2019.02850/full |
work_keys_str_mv |
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