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Efficacy of Post-Infection Passive Immunization with Purified SIVIG J. FISCHER*1, W. SUTTON1, C. PIERCE1, T. MULVANIA2, K. WATANABE2, L. KULLER3, D. ANDERSON3, and N. L. HAIGWOOD1. 1Seattle Biomed. Res. Inst., WA; 2Univ. of Washington, Seattle; and 3Washington Regional Primate Res. Ctr., Seattle The ultimate goal of passive therapy experiments in the macaque model is to provide proof of principle for use of polyclonal or monoclonal Ig in treating HIV infection, particularly for infants born to infected mothers or adults in needle-stick accidents. To develop clinically effective reagents, the efficacy, specificity and magnitude of IgG products need to be defined in a disease model. The SIV/macaque AIDS model provides a chance to evaluate therapeutic efficacy of neutralizing antibody administered passively during primary viremia. SIVIG-NP, IgG purified from SIV-infected macaques classified as nonprogressors to disease for 3 or more years post-infection, demonstrates moderate neutralizing activity against SIVsmE660. 20 Macaca nemestrina were infected IV with 50 MID SIVsmE660. Treated animals received SIVIG-NP (n=10) or normal IgG (n=4) at 200 mg/kg by IV infusion 1 and 14 days post-infection, while 6 infected animals received no intervention. SIVIG-NP transiently suppressed primary viremia and ameliorated post-acute CD4+ cell decline. SIVIG-NP treatment delayed de novo antibody development, but altered neither the kinetics nor magnitude of cell-mediated immunity, as determined by CTL activity. Normal Ig altered neither viremia nor virus-specific immunity compared to untreated controls. One SIVIG-treated and 1 control animal progressed rapidly to disease, with no evidence of SIV-specific immune responses. Four other control animals progressed to disease and euthanasia by 32 weeks post-infection. 32 weeks post-infection, 6 of 9 SIVIG-treated animals showed no CD4+ cell decline, while only 1 of 5 control animals maintained CD4+ cell counts>500. These experiments demonstrate that polyclonal Abs administered immediately post-exposure to a lentivirus can diminish viral replication and delay disease. Results confirm that neutralizing antibodies can play an important role in the host response to SIV. Characterizing SIVIG-NP specificity, dosage, neutralizing capacity, and administration timing will help define qualities critical for therapeutically effective HIV-specific monoclonal or polyclonal preparations. Key Words: antibodies, passive immunity, SIV |
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© 7th
Conference on Retroviruses and Opportunistic Infections, |