MAIT cell activation augments adenovirus vector vaccine immunogenicity

Mucosal-associated invariant T (MAIT) cells are innate sensors of viruses and can augment early immune responses and contribute to protection. We hypothesized that MAIT cells may have inherent adjuvant activity in vaccine platforms that use replication-incompetent adenovirus vectors. In mice and hum...

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Main Authors: Provine, N, Amini, A, Garner, L, Spencer, A, Dold, C, Hutchings, C, Silva Reyes, L, Fitzpatrick, M, Chinnakannan, S, Oguti, B, Raymond, M, Ulaszewska, M, Troise, F, Sharpe, H, Morgan, S, Hinks, T, Lambe, T, Capone, S, Folgori, A, Barnes, E, Rollier, C, Pollard, A, Klenerman, P
Format: Journal article
Language:English
Published: American Association for the Advancement of Science 2021
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author Provine, N
Amini, A
Garner, L
Spencer, A
Dold, C
Hutchings, C
Silva Reyes, L
Fitzpatrick, M
Chinnakannan, S
Oguti, B
Raymond, M
Ulaszewska, M
Troise, F
Sharpe, H
Morgan, S
Hinks, T
Lambe, T
Capone, S
Folgori, A
Barnes, E
Rollier, C
Pollard, A
Klenerman, P
author_facet Provine, N
Amini, A
Garner, L
Spencer, A
Dold, C
Hutchings, C
Silva Reyes, L
Fitzpatrick, M
Chinnakannan, S
Oguti, B
Raymond, M
Ulaszewska, M
Troise, F
Sharpe, H
Morgan, S
Hinks, T
Lambe, T
Capone, S
Folgori, A
Barnes, E
Rollier, C
Pollard, A
Klenerman, P
author_sort Provine, N
collection OXFORD
description Mucosal-associated invariant T (MAIT) cells are innate sensors of viruses and can augment early immune responses and contribute to protection. We hypothesized that MAIT cells may have inherent adjuvant activity in vaccine platforms that use replication-incompetent adenovirus vectors. In mice and humans, ChAdOx1 (chimpanzee adenovirus Ox1) immunization robustly activated MAIT cells. Activation required plasmacytoid dendritic cell (pDC)–derived interferon (IFN)–α and monocyte-derived interleukin-18. IFN-α–induced, monocyte-derived tumor necrosis factor was also identified as a key secondary signal. All three cytokines were required in vitro and in vivo. Activation of MAIT cells positively correlated with vaccine-induced T cell responses in human volunteers and MAIT cell–deficient mice displayed impaired CD8+ T cell responses to multiple vaccine-encoded antigens. Thus, MAIT cells contribute to the immunogenicity of adenovirus vectors, with implications for vaccine design.
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spelling oxford-uuid:f5f9da28-b762-401d-9f2b-fe76f545e4362022-03-27T12:31:39ZMAIT cell activation augments adenovirus vector vaccine immunogenicityJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f5f9da28-b762-401d-9f2b-fe76f545e436EnglishSymplectic ElementsAmerican Association for the Advancement of Science2021Provine, NAmini, AGarner, LSpencer, ADold, CHutchings, CSilva Reyes, LFitzpatrick, MChinnakannan, SOguti, BRaymond, MUlaszewska, MTroise, FSharpe, HMorgan, SHinks, TLambe, TCapone, SFolgori, ABarnes, ERollier, CPollard, AKlenerman, PMucosal-associated invariant T (MAIT) cells are innate sensors of viruses and can augment early immune responses and contribute to protection. We hypothesized that MAIT cells may have inherent adjuvant activity in vaccine platforms that use replication-incompetent adenovirus vectors. In mice and humans, ChAdOx1 (chimpanzee adenovirus Ox1) immunization robustly activated MAIT cells. Activation required plasmacytoid dendritic cell (pDC)–derived interferon (IFN)–α and monocyte-derived interleukin-18. IFN-α–induced, monocyte-derived tumor necrosis factor was also identified as a key secondary signal. All three cytokines were required in vitro and in vivo. Activation of MAIT cells positively correlated with vaccine-induced T cell responses in human volunteers and MAIT cell–deficient mice displayed impaired CD8+ T cell responses to multiple vaccine-encoded antigens. Thus, MAIT cells contribute to the immunogenicity of adenovirus vectors, with implications for vaccine design.
spellingShingle Provine, N
Amini, A
Garner, L
Spencer, A
Dold, C
Hutchings, C
Silva Reyes, L
Fitzpatrick, M
Chinnakannan, S
Oguti, B
Raymond, M
Ulaszewska, M
Troise, F
Sharpe, H
Morgan, S
Hinks, T
Lambe, T
Capone, S
Folgori, A
Barnes, E
Rollier, C
Pollard, A
Klenerman, P
MAIT cell activation augments adenovirus vector vaccine immunogenicity
title MAIT cell activation augments adenovirus vector vaccine immunogenicity
title_full MAIT cell activation augments adenovirus vector vaccine immunogenicity
title_fullStr MAIT cell activation augments adenovirus vector vaccine immunogenicity
title_full_unstemmed MAIT cell activation augments adenovirus vector vaccine immunogenicity
title_short MAIT cell activation augments adenovirus vector vaccine immunogenicity
title_sort mait cell activation augments adenovirus vector vaccine immunogenicity
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