PASSIVE IGG THERAPY IN SIV INFECTED MACAQUES

University Of Washington, Seattle WA

Investigators

Linked publications & trials

Abstract

We have shown that polyclonal IgG from SIV-infected macaques can be given therapeutically during the first 4 weeks of SIV infection and can significantly prolong survival and lengthen time to disease. The major goals of this project are to use passive transfer to test IgG for the ability to affect virus load and host immunological profiles in infected macaques in t he acute stage of infection. We plan to determine the quantitative and qualitative differences in host immune responses in passive-Ig-treated macaques that correlate with changes in virus load or lymphocyte subsets. During the past year, we demonstrated that neutralizing antibodies purified from HIV-1-infected chimpanzees can block SHIV infection in macaques and directly limit the infectivity of virus in vivo. Key to the success of this prophylactic work was the dose of the IgG, which was in the range of 200 mg/kg. The prior successful therapeutic work utilized 170 mg/kg. These data support the developmen t of IgG therapy for needlestick exposure or perinatal transmission. We will be initiating an early treatment experiment in 1999 to test the efficacy of SIVIG versus normal IgG in SIV-infected macaques to further expand on our prior work. FUNDING NIH grant RR00166. Haigwood, N.L. and Zolla-Pazner, S. Humoral immunity to HIV, SIV, and SHIV. AIDS 12:S121-S132, 1998. Igarashi, T., Brown, C., Azadegan, A., Haigwood, N., Martin, M., and Shibata, R. Human immunodeficiency virus type 1 neutralizing antibodies accelerate clearance of cell-free virions from blood plasma. Nature Med. 5 211-216, 1999. Shibata, R., Igarashi, T., Haigwood, N., Buckler-White, A., Ogert, R., Ross, W., Willey, R., Cho, M.W., and Martin, M.A. Neutralizing antibody directed against the HIV-1 envelope glycoproteiin can completely block HIV-1/SIV chimeric virus infections of macaque monkeys. Nature Med. 5 204-210, 1999.