MAIT cell activation augments adenovirus vector vaccine immunogenicity

Science. 2021 Jan 29;371(6528):521-526. doi: 10.1126/science.aax8819.

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 types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Interferon-alpha
  • Interleukin-18
  • Tumor Necrosis Factor-alpha
  • Viral Vaccines