Protection of macaques against vaginal transmission of a pathogenic HIV-1/SIV chimeric virus by passive infusion of neutralizing antibodies

The development of the human immunodeficiency virus-1 (HIV-1)/simian immuno deficiency virus (SIV) chimeric virus macaque model (SHIV) permits the in v ivo evaluation of anti-HIV-1. envelope glycoprotein immune responses(1-3), Using this model, others, and we have shown that passively infused antibody can protect against an intravenous challenge(4,5). However, HIV-1 is most often transmitted across mucosal surfaces(6-9) and the intravenous challeng e model may not accurately predict the role of antibody in protection again st mucosal exposure. After controlling the macaque estrous cycle with proge sterone(10), anti-HIV-1 neutralizing monoclonal antibodies 2F5 and 2G12, an d HIV immune globulin were tested(11-13). Whereas all five control monkeys displayed high plasma viremia and rapid CD4 cell decline, 14 antibody-treat ed macaques were either completely protected against infection or against p athogenic manifestations of SHIV-infection. Infusion of all three antibodie s together provided the greatest amount of protection, but a single monoclo nal antibody, with modest virus neutralizing activity, was also protective. Compared with our previous intravenous challenge study with the same virus and antibodies: the data indicated that greater protection was achieved af ter vaginal challenge. This study demonstrates that antibodies can affect t ransmission and subsequent disease course after vaginal SHIV-challenge; the data begin to define the type of antibody response that could play a role in protection against mucosal transmission of HIV-1.