HIV-inhibitory activity profile of antibodies and correlates of protection

HOLL, V; SCHMIDT, S; LAUMOND, G; DECOVILLE, T; LEDERLE, A; PENICHON, J; PROUST, A; BIEDMA, M.E; SU, B; MOOG, C

Estrasburgo

Conferencia; Europrise: Antibodies beyond binding; 2011

Fcγ receptors (Fcγ) are differentially expressed on a variety of cells of the immune system. Theseinclude monocytes, macrophages, dendritic cells, granulocytes, natural killer and also some cellsof the adaptive immunity, like B cells. FcγRs can bind to different sub-classes of IgG at their Fcpart, and these Fc- FcγR interactions mediate the activation of the FcγR-bearing cell and theirbiological functions.Several assays have been developed to evaluate the participation of FcγRs-bearing cells in HIV-1inhibition by neutralizing as well non-neutralizing antibodies. In addition to the neutralization,other inhibitory activities-induced by these anti-HIV-1 antibodies have been detected in vitro invarious assays and may have a potential impact on sterilizing HIV-1 protection. The activities ofvarious HIV-1-specific antibodies were assessed in unconventional assays using macrophagesand dendritic cells as HIV-1 target cells. It appears that additional HIV-inhibitory activities havebeen detected, that are distinct from the classical HIV-1 neutralization or ADCC, and in whichFcγRs (in particular FcγR I and II) are involved. These assays have highlighted that someunconventional inhibitory antibodies can have strong HIV-inhibition activities in a similarmanner like neutralizing antibodies when macrophages or dendritic cells are the targets. We haveshown that in vitro functional HIV-1 inhibitory profile may vary according to the type of theantibody and the type of the cell that is targeted.A specific combination of such antibodies may be particularly beneficial by cumulating theirinhibitory activities for efficient protection against HIV infection.