Protection of macaques against pathogenic simian/human immunodeficiency virus 89.6PD by passive transfer of neutralizing antibodies

The role of antibody in protection against human immunodeficiency virus (HI V-1) has been difficult to study in animal models because most primary HIV- 1 strains do not infect nonhuman primates. Using a chimeric simian/human im munodeficiency virus (SHIV) based on the envelope of a primary isolate (HIV -89.6), we performed passive-transfer experiments in rhesus macaques to stu dy the role of anti-envelope antibodies in protection. Based on prior in vi tro data showing neutralization synergy by antibody combinations, we evalua ted HIV immune globulin (HIVIG), and human monoclonal antibodies (MAbs) 2F5 and 2G12 given alone, compared with the double combination 2F5/2G12 and th e triple combination HIVIG/2F5/2G12. Antibodies were administered 24 h prio r to intravenous challenge with the pathogenic SHIV-89.6PD. Six control mon keys displayed high plasma viremia, rapid CD4(+)-cell decline, and clinical AIDS within 14 weeks. Of six animals given HIVIG/2F5/2G12, three were comp letely protected; the remaining three animals became SHIV infected but disp layed reduced plasma viremia and near normal CD4(+)-cell counts. One of thr ee monkeys given 2F5/2G12 exhibited only transient evidence of infection; t he other two had marked reductions in viral load. All monkeys that received HMG, 2F5, or 2G12 alone became infected and developed high-level plasma vi remia. However, compared to controls, monkeys that received HIVIG or MAb 2G 12 displayed a less profound drop in CD4(+) T cells and a more benign clini cal course. These data indicate a general correlation between in vitro neut ralization and protection and suggest that a vaccine that elicits neutraliz ing antibody should have a protective effect against HIV-1 infection or dis ease.