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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.

Original publication

DOI

10.1126/science.aax8819

Type

Journal article

Journal

Science

Publication Date

29/01/2021

Volume

371

Pages

521 - 526

Keywords

Adenoviridae, Animals, CD8-Positive T-Lymphocytes, Dendritic Cells, Genetic Vectors, Humans, Immunogenicity, Vaccine, Interferon-alpha, Interleukin-18, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Mucosal-Associated Invariant T Cells, Tumor Necrosis Factor-alpha, Viral Vaccines