Open AccessHLA-I Associated Adaptation Dampens CD8 T-Cell Responses in HIV Ad5-Vectored Vaccine Recipients
Author(s) -
Sushma Boppana,
Sarah Sterrett,
Jacob K. Files,
Kai Qin,
Andrew Fioré-Gartland,
Kristen W. Cohen,
Stephen C. De Rosa,
Anju Bansal
Publication year - 2019
Publication title -
the journal of infectious diseases (online. university of chicago press)/the journal of infectious diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.69
H-Index - 252
eISSN - 1537-6613
pISSN - 0022-1899
DOI - 10.1093/infdis/jiz368
Subject(s) - virology , human leukocyte antigen , immunology , cd8 , human immunodeficiency virus (hiv) , biology , immune system , antigen
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.