Transcriptomic analysis reveals a previously unknown role for CD8+ T-cells in rVSV-EBOV mediated protection

Abstract Ebola virus (EBOV) poses a significant threat to human health as highlighted by the recent epidemic in West Africa. Data from animal studies and a ring vaccination clinical trial conducted in Guinea during the recent epidemic demonstrated that a recombinant VSV where G protein is replaced w...

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Autores principales:	Andrea R. Menicucci, Suhas Sureshchandra, Andrea Marzi, Heinz Feldmann, Ilhem Messaoudi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4b77c33de9834ef5828488469523c3c1
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spelling	oai:doaj.org-article:4b77c33de9834ef5828488469523c3c12021-12-02T15:06:09ZTranscriptomic analysis reveals a previously unknown role for CD8+ T-cells in rVSV-EBOV mediated protection10.1038/s41598-017-01032-82045-2322https://doaj.org/article/4b77c33de9834ef5828488469523c3c12017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01032-8https://doaj.org/toc/2045-2322Abstract Ebola virus (EBOV) poses a significant threat to human health as highlighted by the recent epidemic in West Africa. Data from animal studies and a ring vaccination clinical trial conducted in Guinea during the recent epidemic demonstrated that a recombinant VSV where G protein is replaced with EBOV GP (rVSV-EBOV) is safe and highly efficacious. We previously established that antibodies are essential for rVSV-EBOV mediated protection against EBOV; however, the mechanisms by which this vaccine induces a humoral response and the role of T-cells in rVSV-EBOV mediated protection remain poorly understood. Since this is the only vaccine platform that has completed Phase III clinical studies, it is imperative to gain a better understanding of its mechanisms of protection. Therefore, we performed a longitudinal gene expression analysis of samples collected from controls and T-cell-depleted macaques after rVSV-EBOV vaccination and EBOV challenge. We show that rVSV-EBOV vaccination induces gene expression changes consistent with anti-viral immunity and B-cell proliferation. We also report a previously unappreciated role for CD8+ T-cells in mediating rVSV-EBOV protection. Finally, limited viral transcription in surviving animals may boost protective responses after EBOV challenge by maintaining transcriptional changes. This study presents a novel approach in determining mechanisms of vaccine efficacy.Andrea R. MenicucciSuhas SureshchandraAndrea MarziHeinz FeldmannIlhem MessaoudiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Andrea R. Menicucci Suhas Sureshchandra Andrea Marzi Heinz Feldmann Ilhem Messaoudi Transcriptomic analysis reveals a previously unknown role for CD8+ T-cells in rVSV-EBOV mediated protection
description	Abstract Ebola virus (EBOV) poses a significant threat to human health as highlighted by the recent epidemic in West Africa. Data from animal studies and a ring vaccination clinical trial conducted in Guinea during the recent epidemic demonstrated that a recombinant VSV where G protein is replaced with EBOV GP (rVSV-EBOV) is safe and highly efficacious. We previously established that antibodies are essential for rVSV-EBOV mediated protection against EBOV; however, the mechanisms by which this vaccine induces a humoral response and the role of T-cells in rVSV-EBOV mediated protection remain poorly understood. Since this is the only vaccine platform that has completed Phase III clinical studies, it is imperative to gain a better understanding of its mechanisms of protection. Therefore, we performed a longitudinal gene expression analysis of samples collected from controls and T-cell-depleted macaques after rVSV-EBOV vaccination and EBOV challenge. We show that rVSV-EBOV vaccination induces gene expression changes consistent with anti-viral immunity and B-cell proliferation. We also report a previously unappreciated role for CD8+ T-cells in mediating rVSV-EBOV protection. Finally, limited viral transcription in surviving animals may boost protective responses after EBOV challenge by maintaining transcriptional changes. This study presents a novel approach in determining mechanisms of vaccine efficacy.
format	article
author	Andrea R. Menicucci Suhas Sureshchandra Andrea Marzi Heinz Feldmann Ilhem Messaoudi
author_facet	Andrea R. Menicucci Suhas Sureshchandra Andrea Marzi Heinz Feldmann Ilhem Messaoudi
author_sort	Andrea R. Menicucci
title	Transcriptomic analysis reveals a previously unknown role for CD8+ T-cells in rVSV-EBOV mediated protection
title_short	Transcriptomic analysis reveals a previously unknown role for CD8+ T-cells in rVSV-EBOV mediated protection
title_full	Transcriptomic analysis reveals a previously unknown role for CD8+ T-cells in rVSV-EBOV mediated protection
title_fullStr	Transcriptomic analysis reveals a previously unknown role for CD8+ T-cells in rVSV-EBOV mediated protection
title_full_unstemmed	Transcriptomic analysis reveals a previously unknown role for CD8+ T-cells in rVSV-EBOV mediated protection
title_sort	transcriptomic analysis reveals a previously unknown role for cd8+ t-cells in rvsv-ebov mediated protection
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/4b77c33de9834ef5828488469523c3c1
work_keys_str_mv	AT andrearmenicucci transcriptomicanalysisrevealsapreviouslyunknownroleforcd8tcellsinrvsvebovmediatedprotection AT suhassureshchandra transcriptomicanalysisrevealsapreviouslyunknownroleforcd8tcellsinrvsvebovmediatedprotection AT andreamarzi transcriptomicanalysisrevealsapreviouslyunknownroleforcd8tcellsinrvsvebovmediatedprotection AT heinzfeldmann transcriptomicanalysisrevealsapreviouslyunknownroleforcd8tcellsinrvsvebovmediatedprotection AT ilhemmessaoudi transcriptomicanalysisrevealsapreviouslyunknownroleforcd8tcellsinrvsvebovmediatedprotection
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Transcriptomic analysis reveals a previously unknown role for CD8+ T-cells in rVSV-EBOV mediated protection

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