HLA-I associated adaptation dampens the CD8 T-cell response in HIV Ad5-vectored vaccine recipients.

Abstract

HLA-I associated HIV adaptation is known to negatively impact disease progression and CD8 T-cell responses. We aimed to assess how HLA-I associated adaptation impacts HIV vaccine-induced CD8 T-cell responses in two past vaccine efficacy trials. We found that vaccine-encoded adapted epitopes were less immunogenic than vaccine-encoded non-adapted epitopes, and adapted epitope-specific responses were less polyfunctional than non-adapted epitope-specific responses. Along those lines, vaccine recipients with higher HLA-I adaptation to the Gag vaccine insert mounted less polyfunctional CD8 T-cell responses at the protein-level. Response breadth, which correlated with viral control in recipients who became infected, is also dampened by HLA-I adaptation. These findings suggest that HLA-I associated adaptation is an important consideration for strategies aiming to induce robust CD8 T-cell responses.