IMMUNE-RESPONSES INDUCED BY PROTOTYPE VACCINES FOR AIDS IN RHESUS-MONKEYS

A battery of assay systems was used to profile both humoral and cell-m ediated immune responses induced by immunization with candidate vaccin es consisting of recombinant simian immunodeficiency virus (SIV) glyco proteins rgp110 (nondenatured) with SAF-M adjuvant (gp110 + SAF-M) or rgp140 (denatured) with Freund's adjuvant (gp140 + FA). All of the mon keys became infected after intravenous challenge. However, 16 days fol lowing infection, viral antigenemia was reduced in both groups of vacc inates compared to controls. After 23 days antigenemia in the gp110 SAF-M group remained at the same level as on day 16, whereas antigenem ia in the gp140 + FA group was significantly reduced further than the level observed on day 16. Both vaccines induced blastogenic responses in PBMC cultures stimulated with rgp140, which decreased after repeate d immunizations. Both vaccines induced high ELISA titers of IgG antibo dy against rgpl40 that were equivalent to the titers in asymptomatic l ong-term survivors (LTSs). gp110 +/- SAF-M induced high titers of neut ralizing antibody. In contrast, gp140 + FA failed to induce neutralizi ng antibody, suggesting that the natural conformation of the antigen m ay be essential for the induction of neutralizing antibody. High titer s of antibodies capable of complement-mediated cytolysis (ACC) were in duced by gp110 + SAF-M, whereas minimal ACC antibodies were induced by gp140 + FA. In spite of high titers of antibodies by ELISA, neither g p110 + SAF-M nor gp140 + FA vaccines induced detectable levels of anti body capable of antibody dependent cell-mediated cytolysis (ADCC). Det ectable amounts of MHC class I-restricted, CD8(+) cytotoxic T lymphocy tes (CTLs) were not induced in immunized monkeys before challenge. Aft er challenge and infection, antibody responses to glycoprotein (detect ed by ELISA and ACC) as well as glycoprotein-specific CTLs were induce d in gp140 + FA vaccinates at levels higher than in nonimmunized contr ol animals, indicating a priming effect by gp140 + FA immunization. No priming effect for ADCC antibody induction was observed in monkeys va ccinated with either gp110 + SAF-M or gp140 + FA. Rhesus monkey groups immunized with two different SIV envelope vaccines differed regarding potentially protective humoral and cell-mediated immune responses. Th e physical state of the immunogens, the type of adjuvant used, and/or the immunization protocol apparently affected these responses in both a qualitative and quantitative manner.