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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- Files:
-
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(Preview, Accepted manuscript, pdf, 1.0MB, Terms of use)
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- Publisher copy:
- 10.1126/science.aax8819
Authors
- 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:
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1095-9203
- ISSN:
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0036-8075
- Language:
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English
- Keywords:
- Pubs id:
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1147981
- Local pid:
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pubs:1147981
- Deposit date:
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2020-12-07
- ARK identifier:
Terms of use
- Copyright holder:
- Provine et al.
- Copyright date:
- 2021
- Rights statement:
- Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works https://www.sciencemag.org/about/science-licenses-journal-article-reuse
- Notes:
-
This is the accepted manuscript version of the article. The final version is available from American Association for the Advancement of Science at https://doi.org/10.1126/science.aax8819
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