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Journal article

MAIT cell activation augments adenovirus vector vaccine immunogenicity

Abstract:
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.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1126/science.aax8819

Authors

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Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
NDM Experimental Medicine
Role:
Author


Publisher:
American Association for the Advancement of Science
Journal:
Science More from this journal
Volume:
371
Issue:
6528
Pages:
521-526
Publication date:
2021-01-29
Acceptance date:
2020-11-19
DOI:
EISSN:
1095-9203
ISSN:
0036-8075


Language:
English
Keywords:
Pubs id:
1147981
Local pid:
pubs:1147981
Deposit date:
2020-12-07
ARK identifier:

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