Vaccine induced HIV - 1 envelope gp 120 Constant Region 1 - specific Antibodies

24 Mucosal epithelial cell surface galactosylceramide (Galcer) has been postulated to be a receptor 25 for HIV-1 envelope (Env) interacting with mucosal epithelial cells. Disruption of HIV-1 Env 26 interaction with such alternate receptors could be one strategy to prevent HIV-1 entry through 27 the mucosal barrier. To study antibody modulation of HIV-1 Env-Galcer interactions, we have 28 used Galcer containing liposomes to assess whether naturaland vaccine-induced monoclonal 29 antibodies can block HIV-1 Env binding to Galcer. HIV-1 Env gp140 proteins bound to Galcer 30 liposomes with Kds (Dissociation constant) in nM range. Several HIV-1 ALVAC/AIDSVAX 31 vaccinee-derived mAbs specific for gp120 first constant (C1)-region blocked Galcer binding of a 32 transmitted/founder HIV-1 Env gp140. Among the C1-specific mAbs that showed Galcer 33 blocking, the ADCC-mediating CH38 IgG and its natural IgA isotype were the most potent 34 blocking antibodies. C1-specific IgG monoclonal antibodies that blocked Env binding to Galcer 35 induced up-regulation of the gp120 CD4-inducible (CD4i) epitope bound by mAb 17B, 36 demonstrating that a conformational change in gp120 may be required for Galcer blocking. 37 However, the mAb 17B itself did not block Env-Galcer binding suggesting that the C1-antibody 38 induced gp120 conformational changes resulted in alteration in Galcer binding site distant from 39 the CD4i 17B mAb binding site. 40