STUDIES OF HIGH-DOSES OF A HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 RECOMBINANT GLYCOPROTEIN-160 CANDIDATE VACCINE IN HIV TYPE-1-SERONEGATIVE HUMANS

We examined the safety and immunogenicity of a baculovirus-derived rec ombinant HIV-1 envelope glycoprotein vaccine candidate, rgp160 (VaxSyn ; MicroGeneSys, Meriden, CT), administered at doses of 160 or 640 mu g to 56 healthy, HIV-1-seronegative adults, in a randomized; double-bli nd, placebo-controlled study. Immunizations were given intramuscularly at 0, 1, 6, and 12 months. Both doses were generally well tolerated, although self-limited local reactions were frequent. No other clinical or laboratory toxicities were noted, and no effects on CD4 or CD8 lym phocyte counts or percentages were noted. Serum antibody responses to HIV proteins were detected by Western blot (WE) in 19 of 20 and in 19 of 19 recipients of four doses of 160 and 640 mu g, respectively. West ern blot responses developed more rapidly in the 640-mu g group, High rates of EIA antibody responses to HIV-1 lysate were also present in b oth groups, and developed more rapidly in the 640-mu g group. Enzyme i mmunoassay antibody responses to the immunogen (rgp160) were also freq uent, but were infrequent to V3 to gp41 peptides. Neutralizing antibod ies against the homologous HIV-1 LAI isolate were seen in 3 of 20 subj ects (GMT = 11) who received four doses of 160 mu g, and in 10 of 19 s ubjects who received four doses of 640 mu g (GMT = 32). Fusion inhibit ing antibody was not detected, CD4 blocking activity was seen in 3 of 19 subjects who received four doses of 640 mu g. Complement-mediated a ntibody-dependent enhancement was found in sera from 11 of 19 voluntee rs in the 640-mu g group. Lymphocyte proliferative responses to the im munogen were detected in 4 of 4 subjects tested, but no cytotoxic T ce ll activity was noted in 11 subjects. Administration of the 640-mu g d ose of this rgp160 vaccine candidate relative to the lower doses was a ssociated with increased immunogenicity, including higher rates of hom ologous neutralizing antibody responses, although at low titer.