Transient IL-10 receptor blockade can enhance CD8+T cell responses to a simian adenovirusvectored HIV-1 conserved region immunogen

Abstract

Viral vector vaccines designed to elicit CD8+C T cells in non-human primates exert potent control of immunodeficiency virus infections; however, similar approaches have been unsuccessful in humans. Adenoviral vectors elicit potent T cell responses but also induce production of immunosuppressive interleukin-10 (IL-10), which can limit the expansion of T cell responses. We investigated whether inhibiting IL-10 signaling prior to immunization with a candidate adenovirus vectored-HIV-1 vaccine, ChAdV63.HIVconsv, could modulate innate and adaptive immune responses in BALB/c mice. Transient IL-10 receptor blockade led to a modest but significant increase in the total magnitude CD8+ T cell response to HIVconsv, but did not affect T cell responses to immunodominant epitopes. Anti-IL- 10R-treated animals also exhibited greater expression of CD86 on CD11c+ dendritic cells. Our data support further investigation and optimization of IL-10 blocking strategies to improve the immunogenicity of vaccines based on replication-defective adenoviruses.