J Infect Dis. 2019 Oct 8; 220(10):1620-1628.

PubMed ID: 31301135

HLA-I associated adaptation dampens CD8 T-cell responses in HIV Ad5-vectored vaccine recipients

Boppana S, Sterrett S, Files J, Qin K, Fiore-Gartland A, Cohen KW, De Rosa SC, Bansal A, Goepfert PA

HLA-I-associated human immunodeficiency virus (HIV) adaptation is known to negatively affect disease progression and CD8 T-cell responses. We aimed to assess how HLA-I-associated adaptation affects HIV vaccine-induced CD8 T-cell responses in 2 past vaccine efficacy trials. We found that vaccine-encoded adapted epitopes were less immunogenic than vaccine-encoded nonadapted epitopes, and adapted epitope-specific responses were less polyfunctional than nonadapted 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. Breadth of response, 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.