Abstract
Viral vectors are attractive vaccine platforms that elicit robust innate and adaptive immune responses, but they vary greatly in their ability to induce protective immunity. Adenovirus serotype 5 (Ad5) vectors elicit robust CD8+ T cell responses but are typically characterized by an exhausted phenotype. The mechanisms by which Ad5 vectors induce dysfunctional CD8+ T cells have not been fully elucidated. Here we demonstrate that Ad5 vectors, but not Ad26 vectors, elicit exhausted antigen-specific IL-10+PD1+ CD4+ T cells with a dysfunctional transcriptional profile, and these cells effectively suppress CD8+ T cell responses in vivo. The blockade of IL-10 increased the frequency of antigen-specific CD8+ T cells with enhanced cytokine polyfunctionality and protective capacity against a Listeria monocytogenes challenge. Induction of inhibitory CD4+ T cells by Ad5 vectors is associated with increased IL-27 expression, and IL-27 blockade improves CD4+ T cell cytokine polyfunctionality. Together our data highlight a novel role for IL-27 induced inhibitory CD4+ T cells in regulating responses to viral vector vaccines.
- Copyright © 2016 by The American Association of Immunologists, Inc.