POTENT AND SYNERGISTIC NEUTRALIZATION OF HUMAN-IMMUNODEFICIENCY-VIRUS(HIV) TYPE-1 PRIMARY ISOLATES BY HYPERIMMUNE ANTI-HIV IMMUNOGLOBULIN COMBINED WITH MONOCLONAL-ANTIBODIES 2F5 AND 2G12

Three antibody reagents that neutralize primary human immunodeficiency virus type 1 (HIV-1) isolates were tested for magnitude and breadth o f neutralization when used alone or in double or triple combinations. Hyperimmune anti-HIV immunoglobulin (HIVIG) is derived from the plasma of HIV-1-infected donors, and monoclonal antibodies (MAbs) 2F5 and 2G 12 bind to distinct regions of the HIV-1 envelope glycoprotein. The an tibodies were initially tested against a panel of 15 clade B HIV-1 iso lates, using a single concentration that is achievable in ii ro (HIVIG , 2,500 mu g/ml; MAbs, 25 mu g/ml), Individual antibody reagents neutr alized many of the viruses tested, but antibody potency varied substan tially among the viruses, The virus neutralization produced by double combinations of HIVIG plus 2F5 or 2G12, the two MAbs together, or the triple combination of HIVIG, 2F5, and 2G12 was generally equal to or g reater than that predicted by the effect of individual antibodies, Ove rall, the triple combination displayed the greatest magnitude and brea dth of neutralization, Synergistic neutralization was evaluated by ana lyzing data from dose-response curves of each individual antibody reag ent compared to the triple combination and was demonstrated against ea ch of four viruses tested, Therefore, combinations of polyclonal and m onoclonal anti-HIV antibodies can produce additive or synergistic neut ralization of primary HIV-1 isolates, Passive immunotherapy for treatm ent or prophylaxis of HIV-1 should consider mixtures of potent neutral ising antibody reagents to expand the magnitude and breadth of virus n eutralisation.