Unravelling the antigenic landscape of the HIV-1 subtype A envelope of an individual with broad cross-neutralizing antibodies using phage display peptide libraries

Broad cross-neutralizing antibodies from persons infected with HIV-1 target a variety of epitopes. Identification of these HIV-1 epitopes may result in an optimal panel of antigenic peptides to be included in a prophylactic vaccine. Phage display peptide libraries were used to unravel the antigenic landscape of an individual (ITM1) infected with HIV-1 subtype A with broad cross-neutralizing antibodies. A stringent selection strategy resulted in the identification of 60 unique HIV-1 peptide phage, which were subjected to sequence analysis and mapped onto the ITM1 envelope sequences. Four groups of peptide phages were found: the first group (n = 11) were similar with the tip of the V3 loop (KxxHxGPxxxF); the second group (n = 11) represented the gp41 principal immunodominant domain (CxGxLxCTxNxP); the third group (n = 16) could be localized in the V2 loop (KxxxHxxxY); and the fourth group (n = 22) mimicked a conformational epitope (HxxS/TNxK). All but the V2-binding antibodies were conserved over the 11 years of follow-up. A neutralization inhibition assay revealed the contribution of the V3 antibodies to the neutralizing capacity of the ITM1 plasma. Overall, the ITM1 immunogenic landscape was mapped and a part of the origin of this broad cross-neutralizing activity was demonstrated.