Additive effects characterize the interaction of antibodies involved in neutralization of the primary dualtropic human immunodeficiency virus type 1 isolate 89.6

Human immunodeficiency virus-type I (HIV-1) infection elicits antibodies (A bs) directed against several regions of the gp120 and gp41 envelope glycopr oteins. Many of these Abs are able to neutralize T-cell-line-adapted strain s (TCLA) of HIV-1, but only a few effectively neutralize primary HIV-1 isol ates. The nature of HIV-1 neutralization has been carefully studied using h uman monoclonal Abs (MAbs), and the ability of such MAbs to act in synergy to neutralize HIV-1 has also been extensively studied. However, most synerg y studies have been conducted using TCLA strains. To determine the nature o f Ab interaction in HIV-1 primary isolate neutralization, a panel of 12 ant i-HIV-1 human immunoglobulin G (IgG) MAbs, specific for epitopes in gp120 a nd gp41, were used. Initial tests showed that six of these MAbs, as well as sCD4, used individually, were able to neutralize the dualtropic primary is olate HIV-1(89.6); MAbs giving significant neutralization at 2 to 10 mug/ml included 2F5 (anti-gp41), 50-69 (anti-gp41), IgG1b12 (anti-gp120(CD4bd)), 447-52D (anti-gp120(V3)), 2G12 (anti-gp120), and 670-D (anti-gp120(C5)). Fo r studies of reagent interaction, 16 binary combinations of reagents were t ested for their ability to neutralize HIV-189.6. Reagent combinations teste d included one neutralizing MAb with sCD4, six pairs consisting of two neut ralizing MAbs, and nine pairs consisting of one neutralizing MAb with anoth er non-neutralizing MAb. To assess the interaction of the latter type of co mbination, a new mathematical treatment of reagent interaction was develope d since previously used methods could be used only when both reagents neutr alize. Synergy was noted between sCD4 and a neutralizing anti-gp120(V3) MAb . Antagonism was noted between two pairs of anti-gp41 MAbs (one neutralizin g and one non-neutralizing). All of the other 13 pairs of MAbs tested displ ayed only additive effects. These studies suggest that Abs rarely act in sy nergy to neutralize primary isolate HIV-1(89.6); many anti-HIV-1 Abs act ad ditively to mediate this biological function.