title: HIV-1 neutralizing antibodies elicited by the candidate CBD1 epitope vaccine react with the conserved caveolin-1 binding motif of viral glycoprotein gp41.
abstract: To date, candidate HIV-1 vaccines that have been tested in clinical trials have failed to induce broadly neutralizing activities and/or antibodies that inhibit infection by primary isolates of HIV-1. We recently identified a conserved caveolin-1 binding motif, WNNMTWMQW, in the ectodomain of HIV-1 transmembrane envelope glycoprotein gp41. We designed the synthetic CBD1 peptide SLEQIWNNMTWMQWDK, corresponding to the consensus caveolin-1 binding domain (CBD) in gp41, and showed that it elicits in rabbits the production of antibodies that inhibit infection of primary CD4(+) T lymphocytes by various primary HIV-1 isolates. Although a conserved and highly homologous caveolin-1 binding motif is present in the transmembrane envelope glycoprotein of different HIV-2 isolates, anti-CBD1 immune sera do not inhibit HIV-2 infection. Here we show that anti-CBD1 antibodies are directed against the conserved caveolin-1 binding motif WNNMTWMQW in the CBD1 epitope. In spite of this, anti-CBD1 antibodies do not react with the CBD2 peptide SLTPDWNNMTWQEWER, corresponding to the potential consensus caveolin-1 binding domain in HIV-2. The presence of a conserved proline residue upstream of the caveolin-1 binding motif in CBD2 might affect the presentation of this motif, and thus account for the lack of reactivity of the immune sera. Anti-CBD1 antibodies therefore appear to be directed against a conformational epitope mimicked by the synthetic CBD1 peptide. In accordance with this, anti-CBD1 immune sera react with the native but not denatured gp41. The reactivity of anti-CBD1 immune sera with a highly conserved conformational epitope could explain the broad inhibitory activity of such antipeptide antibodies against HIV-1 isolates of various clades.
authors.affiliation: UFR Biomédicale, Université René Descartes, UPR 2228 CNRS, 45 rue des Saints Pères, 75270 Paris Cedex 6, France.
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Rey-Cuillé
authors.forename: Josette
authors.initials: J
authors.lastname: Svab
authors.forename: Rima
authors.initials: R
authors.lastname: Benferhat
authors.forename: Bernard
authors.initials: B
authors.lastname: Krust
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Briand
authors.forename: Sylviane
authors.initials: S
authors.lastname: Muller
authors.forename: Ara G
authors.initials: AG
authors.lastname: Hovanessian
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D051242:Caveolin 1 / Q000378:metabolism*; D003429:Cross Reactions; D018604:Epitope Mapping; D015483:HIV Antibodies / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D007106:Immune Sera / Q000276:immunology; D008969:Molecular Sequence Data; D011817:Rabbits
chemical_list: D016915:AIDS Vaccines; D051242:Caveolin 1; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; D007106:Immune Sera