Extensive profile of the anti-HIV inhibitory activity of well-known monoclonal antibodies, possible correlates for in vivo protection

BIEDMA, M.E; SCHMIDT, S; DECOVILLE, T; LAUMOND, G; HOLL, V; MOOG, C

Praga

Conferencia; Rational Design of HIV Vaccines and Microbicides; 2011

EUROPRISE

Receptors for immunoglobulins (FcγRs) vary in their cellular distribution and affinity for different IgG isotypes. Fc-FcγR interactions initiate a range of immunoregulatory processes that might also play a role in disease pathogenesis. Particularly, by in vitro assay it has been identified various inhibitory activities antibody-mediated against HIV which may impact on sterilizing protection in vivo. Thus, the aim of this study was to evaluate different immune activities mediated by well known HIV-specific monoclonal antibodies using various effector cells.Neutralizing activity (using TZMbl cell line and PBMCs assay), Fc-mediated inhibitory activity (on macrophages and dendritic cells); Antibody dependant cell mediated citotoxicity (on primary NK effector and HIV-infected target cells) and capture assay of primary isolates were carried out for well known anti-HIV specific Abs.This study shows the different ability of HIV-1 specific antibodies to mediate besides neutralization other alternative immune mechanisms. Inhibitory activities of antibodies were ranked according its capacity to mediate neutralization, Fc-mediated inhibition on macrophages and DCs or other immune process evaluated.The inhibitory profile of each Ab will help to define the key inhibitory activities contributing to in vivo protection. Specific combination of Abs may be particularly favourable by cumulating inhibitory activities leading to efficient protection from HIV infection.