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<jats:title>Abstract</jats:title><jats:p>Mucosal-associated invariant T (MAIT) cells can be activated by viruses through a cytokine-dependent mechanism, and thereby protect from lethal infection. Given this, we reasoned MAIT cells may have a critical role in the immunogenicity of replication-incompetent adenovirus vectors, which are novel and highly potent vaccine platforms. <jats:italic>In vitro</jats:italic>, ChAdOx1 (Chimpanzee Adenovirus Ox1) induced potent activation of MAIT cells. Activation required transduction of monocytes and plasmacytoid dendritic cells to produce IL-18 and IFN-α, respectively. IFN-α-induced monocyte-derived TNF-α was identified as a novel intermediate in this activation pathway, and activation required combinatorial signaling of all three cytokines. Furthermore, ChAdOx1-induced <jats:italic>in vivo</jats:italic> MAIT cell activation in both mice and human volunteers. Strikingly, MAIT cell activation was necessary <jats:italic>in vivo</jats:italic> for development of ChAdOx1-induced HCV-specific CD8 T cell responses. These findings define a novel role for MAIT cells in the immunogenicity of viral vector vaccines, with potential implications for future design.</jats:p><jats:sec><jats:title>One sentence summary</jats:title><jats:p>Robust immunogenicity of candidate adenovirus vaccine vectors requires the activation of unconventional T cells.</jats:p></jats:sec>

Original publication

DOI

10.1101/661397

Type

Journal article

Publisher

Cold Spring Harbor Laboratory

Publication Date

14/06/2019