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

Objective: To assess similarities and differences in antibody responses to recombinant (r) HIV-1(IIIB) gp1 20 in chimpanzees, previously protected from HIV-1 infection, and human volunteers immunized in connection with a Phase I clinical trial. Methods: Frozen sera from humans immunized with rgp120 from HIV-1(IIIB) and chimpanzees immunized with the 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 antibody 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 of HIV-1 and were effective in blocking the binding of gp120 to CD4. Antibody binding to native gp120 was greater than to denatured gp1 20 in both species. Antibody responses to the principal neutralizing determinant (V3 domain) and virus neutralization titers were approximately 10-fold lower in humans than chimpanzees. The relative avidity of antibody binding to gp1 20 was higher in the sera from the immunized chimpanzees than in the immunized humans. Conclusions: While the antibody responses to rgp120 elicited in man and chimpanzees were in many ways similar, significant differences did occur. Predictions made on the basis of chimpanzee immunogenicity studies overestimated the potency of the virus neutralizing titers and under-estimated the duration of the antibody response achieved in humans.