Protective effect of vaginal application of neutralizing and non-neutralizing inhibitory antibodies against vaginal HIV challenge in macaques

MOOG, C; DEREUDDRE-BOSQUET, N; TEILLAUD, J; BIEDMA, M.E; VANHAM, G; HEYNDRICKX, L; VAN DORSSELAER, A; KATINGER, D; VCELAR, B; ZOLLA-PAZNER, S; MANGEOT, I; KELLY, C; SHATTOCK, R; LE GRAND, R

MUCOSAL IMMUNOLOGY

NATURE PUBLISHING GROUP

Lugar: Londres; Año: 2014 p. 46 - 56

1933-0219

Definition of antibody (Ab) functions capable of preventing mucosal HIV transmission maybe critical to both effective vaccine development and the prophylactic use of monoclonal Abs. Although direct antibody mediated neutralization is highly effective against cell free virus, increasing evidence suggests an important role for IgG Fcgamma receptor (FcγR) mediated inhibition of HIV replication. Thus, a panel of well known neutralizing (NAbs) and non neutralizing Abs (NoNAbs) were screened for their ability to block HIV acquisition and replication in vitro in either an independent or FcγR dependent manner. Abs displaying the highest Fc mediated inhibitory activity in various in vitro assays were selected, formulated for topical vaginal application in a Microbicide gel and tested for their anti viral activity against SHIVSF162P3 vaginal challenge in non human primates (NHPs). A combination of three NAbs, 2G12, 2F5 and 4E10, fully prevented SHIV vaginal transmission in 10 out of 15 treated NHPs whereas a combination of two NoNAbs, 246-D and 4B3, although having no impact on SHIV acquisition, reduced plasma viral load. These results indicate that anti HIV Abs with distinct neutralization and inhibitory functions differentially impact in vivo HIV acquisition and replication, by interfering with early viral replication and dissemination. Therefore, combining diverse Ab properties may potentiate the protective effects of anti HIV-Ab based strategies.