Studies of High Doses of a Human Immunodeficiency Virus Type 1 Recombinant Glycoprotein 160 Candidate Vaccine in HIV Type 1-Seronegative Humans

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Abstract
We examined the safety and immunogenicity of a baculovirus-derived recombinant HIV-1 envelope glycoprotein vaccine candidate, rgp160 (VaxSyn; MicroGeneSys, Meriden, CT), administered at doses of 160 or 640 μg to 56 healthy, HIV-1-seronegative adults, in a randomized, double-blind, 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 lymphocyte counts or percentages were noted. Serum antibody responses to HIV proteins were detected by Western blot (WB) in 19 of 20 and in 19 of 19 recipients of four doses of 160 and 640 μg, respectively. Western blot responses developed more rapidly in the 640-μg group. High rates of EIA antibody responses to HIV-1 lysate were also present in both groups, and developed more rapidly in the 640-μg group. Enzyme immunoassay antibody responses to the immunogen (rgp160) were also frequent, but were infrequent to V3 to gp41 peptides. Neutralizing antibodies against the homologous HIV-1 LAI isolate were seen in 3 of 20 subjects (GMT = 11) who received four doses of 160 μg, and in 10 of 19 subjects who received four doses of 640 μg (GMT = 32). Fusion inhibiting antibody was not detected. CD4 blocking activity was seen in 3 of 19 subjects who received four doses of 640 μg. Complement-mediated antibody-dependent enhancement was found in sera from 11 of 19 volunteers in the 640-μg group. Lymphocyte proliferative responses to the immunogen were detected in 4 of 4 subjects tested, but no cytotoxic T cell activity was noted in 11 subjects. Administration of the 640-μg dose of this rgp 160 vaccine candidate relative to the lower doses was associated with increased immunogenicity, including higher rates of homologous neutralizing antibody responses, although at low titer.

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