COMPARISON OF THE IMMUNE-RESPONSE TO RECOMBINANT GP120 IN HUMANS AND CHIMPANZEES

Objective: To assess similarities and differences in antibody response s to recombinant (r) HIV-1(IIIB) gp1 20 in chimpanzees, previously pro tected from HIV-1 infection, and human volunteers immunized in connect ion with a Phase I clinical trial. Methods: Frozen sera from humans im munized with rgp120 from HIV-1(IIIB) and chimpanzees immunized with th e same antigen or recombinant soluble gp160 were compared in a variety of serologic assays. Results: The magnitude of the antibody response to gp120 was similar in both species; however, the half-life of the an tibody response to rgp120 was approximately 4.5 times longer in humans (9 weeks) than in chimpanzees (2 weeks). Antibodies to gp120 in both species were broadly cross-reactive with gp120 from diverse isolates o f HIV-1 and were effective in blocking the binding of gp120 to CD4. An tibody binding to native gp120 was greater than to denatured gp1 20 in both species. Antibody responses to the principal neutralizing determ inant (V3 domain) and virus neutralization titers were approximately 1 0-fold lower in humans than chimpanzees. The relative avidity of antib ody binding to gp1 20 was higher in the sera from the immunized chimpa nzees than in the immunized humans. Conclusions: While the antibody re sponses to rgp120 elicited in man and chimpanzees were in many ways si milar, significant differences did occur. Predictions made on the basi s of chimpanzee immunogenicity studies overestimated the potency of th e virus neutralizing titers and under-estimated the duration of the an tibody response achieved in humans.