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MAIT cell activation augments adenovirus vector vaccine immunogenicity

ABSTRACT: Mucosal-associated invariant T (MAIT) cells are innate sensors of viruses, which can augment early immune responses and contribute to protection from lethal infection. Thus, we reasoned MAIT cells may have an adjuvating role in the immunogenicity of replication-incompetent adenovirus vectors, which are novel vaccine platforms for pandemic pathogens such as Ebola virus and SARS-CoV-2. In both mice and human volunteers, immunization with ChAdOx1 (Chimpanzee Adenovirus Ox1) robustly activated MAIT cells. Activation required transduction of plasmacytoid dendritic cells and monocytes to produce IFN- and IL-18, respectively. IFN--induced monocyte-derived TNF was identified as a novel intermediate in this activation pathway, and activation required combinatorial signaling of all three cytokines both in vitro and in vivo. Strikingly, vaccine-induced activation of MAIT cells positively correlated with vaccine-induced T cell responses in human volunteers. Supporting a causal relationship, MAIT cell-deficient mice displayed impaired CD8+ T cell responses to multiple vaccine-encoded antigens. These findings define a novel role for MAIT cells in the immunogenicity of adenovirus vector vaccines, with potential implications for vaccine design.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE158835 | GEO | 2020/10/01

REPOSITORIES: GEO

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MAIT cell activation augments adenovirus vector vaccine immunogenicity

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