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Protection of Macaques against Vaginal Transmission of a Pathogenic HIV-1/SIV Chimeric Virus (SHIV) by Passive Infusion of Neutralizing Antibodies J. MASCOLA*1, G. STIEGLER2, T. VANCOTT1, H. KATINGER2, C. CARPENTER1, C. HANSON1, H. BEARY1, D. HAYES1, S. FRANKEL1, D. BIRX1, and M. LEWIS1. 1Walter Reed Army Inst. of Res. and Henry M. Jackson Fndn., Rockville, MD; and 2Inst. of Applied Microbiology, Univ. of Agriculture, Vienna, Austria Since HIV-1 infection most often occurs after mucosal exposure, we sought to determine if passively infused neutralizing antibodies could inhibit the vaginal transmission of a pathogenic SHIV. SHIV vaginal challenge experiments were performed after controlling the macaque estrous cycle with progesterone. Two human monoclonal antibodies (MAb 2F5, 2G12) and a polyclonal HIV immune globulin (HIVIG) were tested. Antibodies were infused 24 hours prior to vaginal challenge with SHIV89.6PD. Four groups of rhesus macaques were infused with control IVIG (n=5), MAb 2G12 (n=4), MAb 2G12 + 2F5 (n=5) or HIVIG + 2F5 + 2G12 (n=5). All five IVIG control animals developed high level plasma viremia and rapid CD4 cell decline following vaginal SHIV89.6PD challenge. In contrast, complete protection against infection was achieved in 4 of 5 animals in the HIVIG/2F5/2G12 group, 2 of 5 in the 2F5/2G12 group and 2 of 4 in the 2G12 alone group. Compared to controls, antibody treated animals that became SHIV-infected, displayed substantially lower plasma RNA levels and higher peripheral CD4 counts. Of note, the protection achieve by a single MAb (2G12), with only modest in-vitro neutralizing activity, suggests that even modest levels of functional anti-HIV-1 antibody can affect infection and disease. Also, compared to our prior intravenous challenge study with the same virus and antibodies, greater protection was observed after vaginal challenge. These data suggest that antibody can more readily impact infection and disease when virus exposure occurs across the vaginal mucosa, perhaps by interrupting the initial events associated with mucosal transmission and regional spread of HIV-1. This study demonstrates that antibodies can affect transmission 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. Key Words: Antibody, Vaccine |
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© 7th
Conference on Retroviruses and Opportunistic Infections, |