We have evaluated 2 congenic attenuated clones that vary in tropism for their ability to cause disease in the infected monkey, and to induce immune responses that are protective. The clones were Ron Desrosiers' SIVmac239nef, which is T-cell tropic, and SIV/17E-Cl, which is macrophage-tropic. The immune responses induced by these clones are distinct from one another, with SIV/17E-Cl driving primarily Th1 type responses (e.g., class I restricted CTL), while SIVmac239nef generated a TH2 type response characterized by higher antibody titers, but no detectable CTL. SIV/17E-Cl also readily induced high levels of type-specific neutralizing antibody early in infection (detectable at 3 weeks postinfection) that by 8 months, broadened to include neutralization of the primary heterologous isolate, SIV/DeltaB670. In contrast, no neutralizing antibody response was detected against any SIV isolate in the SIVmac239nef-infected group during this time frame. The mechanism(s) of protection induced by the 2 congenic clones remain unclear, and may (in fact, likely) involve different mechanisms. Thus, we propose to evaluate the role of antibody in the protection induced by these viruses in the passive protection study described below. The study will consist of 5 arms with 4 monkeys/arm. Each monkey will receive IgG purified from a pool of sera from animals infected with the following viruses 1. SIV/17E-Cl, with no change in lymphocyte subsets 2. SIV/17E-Cl, with declines in CD4 3. SIVmac239nef. 4. monkey J587, a long-term nonprogressor of SIV/DeltaB670 infection 5. uninfected monkey serum control. Each animal will receive an infusion of Ig equivalent to 3 log2 dilutions higher than that seen in the monkeys infected with the respective strains to accomodate the dilution effect once in the animal. The following day, monkeys will be challenged intravenously with 50 I.V. doses of SIV/DeltaB670. Challenged animals will be monitored for infection by PCR and virus isolation. The genotype of the virus found in infected monkeys, if present, will be confirmed by direct PCR amplification of the viral gp120 V1-V2 region from PBMC's, followed by cloning and sequence analysis of 10-15 clones. We are currently collecting and pooling serum from the donor animals for the proposed studies. Since the required material is purified immunoglobulin from these samples, a large bank of serum will be required.
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