Combined mTOR inhibition and OX40 agonism enhances CD8(+) T cell memory and protective immunity produced by recombinant adenovirus vaccines.

ABSTRACT: The memory CD8(+) T cell population elicited by immunization with recombinant human adenovirus serotype 5 (rHuAd5) vaccines is composed primarily of effector and effector memory cells (T(EM)) with limited polyfunctionality. In this study, we investigated whether treatment with immunomodulators could enhance and/or redistribute the CD8(+) memory population elicited by rHuAd5. Vaccination in combination with both rapamycin (to modulate differentiation) and an OX40 agonist (to enhance costimulation) increased both the quantity and polyfunctionality of the CD8(+) memory T cell population, with expansion of the T(EM) and memory precursor populations. Furthermore, this intervention enhanced protection against multiple virus challenges. Attenuation of adenovirus transgene expression was required

SUBMITTER: Bassett JD 

PROVIDER: S-EPMC3321597 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature