SYNERGISTIC NEUTRALIZATION OF A CHIMERIC SIV HIV TYPE-1 VIRUS WITH COMBINATIONS OF HUMAN ANTI-HIV TYPE-1 ENVELOPE MONOCLONAL-ANTIBODIES OR HYPERIMMUNE GLOBULINS/

A panel of 14 human IgG monoclonal antibodies (MAbs) specific for enve lope antigens of the human immunodeficiency virus type 1 (HIV-1), 2 hi gh-titer human anti-HIV-1 immunoglobulin (HIVIG) preparations, and 15 combinations of MAbs or MAb/HIVIG were tested for their ability to neu tralize infection of cultured human T cells (MT-2) with a chimeric sim ian immunodeficiency virus (SHIV-vpu(+)), which expressed HIV-1 IIIB e nvelope antigens, Eleven MAbs and both HIVIGs were neutralizing, When used alone, the anti-CD4-binding site MAb b12, the anti-gp41 MAb 2F5, and the anti-gp120 MAb 2G12 were the most potent, When combination reg imens involving two MAbs targeting different epitopes were tested, syn ergy was seen in all paired MAbs, except for one combination that reve aled additive effects, The lowest effective antibody concentration for 50% viral neutralization (EC50) and EC90 were achieved with combinati ons of MAbs b12, 2F5, 2G12, and the anti-V3 MAb 694/98D, Depending on the combination regimen, the concentration of MAbs required to reach 9 0% virus neutralization was reduced approximately 2- to 25-fold as com pared to the dose requirement of individual MAbs to produce the same e ffect, Synergy of the combination regimens implies that combinations o f antibodies may have a role in passive immunoprophylaxis against HIV- 1, The ability of SHIV to replicate in rhesus macaques will allow us t o test such approaches in vivo.