Analysis of the exposure of induced HIV glycoprotein epitopes in a potential HIV pseudovirion vaccine.
Functionally conserved HIV-Env epitopes, which are induced during the process of Env-mediated membrane fusion, represent interesting immunogens, which may elicit broad neutralising antibody responses. In this report, we analyse a pseudovirion (PV)-based HIV vaccine preparation, potentially enriched in such induced Env-conformations. The vaccine has been prepared by mixing and incubating Env-PVs, with incorporated fusion-defective Env, with PVs, which have incorporated functional CD4 and CXCR4 proteins. Here, we demonstrate that three different monoclonal antibodies (CG10, 17b and 48d), recognising a region of gp120 overlapping with the coreceptor binding site, and a further antibody, 8F101, recognising a CD4-induced epitope outside of the coreceptor site, bind to Env molecules in the putative PV vaccine mixture but not at all, or less strongly, to native Env-PVs. In all cases, antibody binding required an interaction of the Env-PVs with CD4 whereas CXCR4 was dispensible. These results confirm that in the PV vaccine preparation, CD4-induced Env epitopes are accessible and that these, as well as other induced epitopes "downstream" from CD4 binding, may function as immunogens to elicit potentially cross-neutralising humoral immune responses.
Devitt
Gerard
G
Deutsches Krebsforschungszentrum, F020, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany.
Emerson
Vanessa
V
Pisch
Thorsten
T
Keppler
Oliver T
OT
Bosch
Valerie
V
D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015704:CD4 Antigens / Q000378:metabolism; D000939:Epitopes / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology*; D006678:HIV / Q000235:genetics / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology; D051379:Mice; D019718:Receptors, CXCR4 / Q000378:metabolism; D011994:Recombinant Proteins / Q000276:immunology; D014771:Virion / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D000939:Epitopes; D006023:Glycoproteins; D015699:HIV Envelope Protein gp120; D019718:Receptors, CXCR4; D011994:Recombinant Proteins