Adenovirus Type 5 Induces Vitamin A–Metabolizing Enzymes in Dendritic Cells and Enhances Priming of Gut Homing CD8 T Cells

Protective immunity at the gut-associated mucosal tissue is induced primarily by oral/rectal immunization owing to the need for targeting antigen to the gut-resident dendritic cells (DC). Here we show that an adenovirus type 5 (Ad5) based HIV-1 vaccine can prime a durable antigen-specific CD8 T cell response in the gut following intramuscular immunization in mice. The ability of Ad5 to prime gut homing CD8 T cells in vivo was associated with Ad5-induced expression of retinal dehydrogenase (RALDH) enzymes in conventional DC. The Ad5-mediated induction of RALDH did not require signaling through toll-like receptors, DNA-dependent activator of IRFs and several MAP kinases, or replication capacity of the virus, but was dependant on NF-κB and granulocyte-macrophage colony-stimulating factor. These results provide an innate mechanism through which Ad5-stimulated DC prime gut homing CD8 T cells and have implications for the development of novel mucosal adjuvants for subunit vaccines administered via the intramuscular route.