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 (Hxx(S)/(T)NxK). 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.
Dieltjens
Tessa
T
Department of Microbiology, Institute of Tropical Medicine, Nationalestraat 155, 2000 Antwerp, Belgium. tdieltjens@itg.be
Willems
Betty
B
Coppens
Sandra
S
Van Nieuwenhove
Lies
L
Humbert
Michael
M
Dietrich
Ursula
U
Heyndrickx
Leo
L
Vanham
Guido
G
Janssens
Wouter
W
D057134:Antibodies, Neutralizing / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology*; D018604:Epitope Mapping; D015483:HIV Antibodies / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D019151:Peptide Library; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
D057134:Antibodies, Neutralizing; D000956:Antigens, Viral; D015483:HIV Antibodies; D019151:Peptide Library; D054299:env Gene Products, Human Immunodeficiency Virus