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

par Dieltjens, Tessa;Willems, Betty;Coppens, Sandra ;Van Nieuwenhove, Lies;Humbert, Michael;Dietrich, Ursula;Heyndrickx, Leo;Vanham, Guido;Janssens, Wouter
Référence Journal of virological methods, 169, 1, page (95-102)
Publication Publié, 2010-10

Article révisé par les pairs

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Résumé :

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. © 2010 Elsevier B.V.