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Objective: To evaluate the safety and immunogenicity of recombinant glycoprotein (rgp) 120, a candidate vaccine for the human immunodeficiency virus (HIV), formulated with a novel adjuvant, MF59, with or without a biological response modifier, MTP-PE. Design: Multicenter, double-blind, randomized trial. Setting: University medical centers. Participants: 49 healthy, HlV-seronegative volunteers 18 to 60 years of age who were at low risk for HIV type 1 (HIV-1) infection. Interventions: In part A of the study, 32 participants were randomly assigned to receive either 15 [micro]g of rgp120 in MF59, 15[micro]g of rgp120 in MF59 plus 50 [micro]g of MTP-PE, 50 [micro]g of rgp120 in MF59, or 50 [micro]g of rgp120 in MF59 plus 50 [micro]g of MTP-PE. Participants were vaccinated at 0, 1, 6, and 12 to 18 months. In part B, 17 participants were randomly assigned to receive five monthly injections of either 50 [micro]g of rgp120 in MF59 or MF59 alone followed by a booster injection at 12 to 18 months. Main Outcome Measures: Local and systemic reactions; laboratory measures of hepatic, renal, immunologic, and bone marrow toxicity; and HlV-specific serologic and cell-mediated immune responses. Results: 13 patients in part A received 50-[micro]g doses of rgp120; type-specific neutralizing antibody responses against the SF-2 strain of HIV-1 (HIV-1/SF-2) were induced in all 13. Nine of the 13 had crossreactive neutralizing activity against the MN strain of HIV-1 (HIV-1/MN), and 2 had crossreactive neutralizing activity against the IIIB strain of HIV-1 (HIV-1/lIlB). Twelve patients had type specific fusion inhibition activity; only 1 had crossreactive fusion inhibition activity against HIV-1/MN. The monthly vaccination schedule used in part B resulted in decreased antibody titers, indicating that a rest period in the schedule is necessary for maximal immunogenicity. Lymphoproliferative responses against gp120 were induced in all vaccine recipients. The stimulation index to gp120 was persistently greater than 15 for 6 months after the last booster vaccination was given. CD8+ cytotoxic T-lymphocyte activity was detected in 1 of the 11 participants tested. Vaccine that contained MTP-PE caused a greater number of moderate or severe local and systemic reactions (of 16 participants, 4 had local reactions and 13 had systemic reactions) than did vaccine formulated with MF59 alone (of 16 participants, 7 had local reactions [P < 0.01] and 0 had systemic reactions [P < 0.001]). Conclusions: The SF-2 rgp120 vaccine is safe and immunogenic. Three vaccinations with rgp120 in MF59 can induce type-specific and crossreactive neutralizing antibody against B-subtype laboratory strains of HIV-1. Human immunodeficiency virus-specific Iymphoproliferative responses were induced in all vaccinated participants, and CD8+ cytotoxic T-lymphocyte activity was shown in one participant. A trend toward the augmentation of Iymphoproliferative and humoral responses by MTP-PE was seen in the participants receiving 15 [micro]g of rgp120. However, MTP-PE caused a statistically significant increase in the incidence of local and systemic side effects, which was felt to outweigh the small increase in immunogenicity provided by this biological response modifier in an otherwise well-tolerated vaccine., Recombinant glycoprotein (rgp) 120 may be a safe and effective vaccine for the human immunodeficiency virus (HIV). Glycoprotein 120 is an especially promising vaccine antigen because it plays a role in initiating HIV infection, causes attachment to susceptible cells and is a target for neutralizing antibodies. The vaccination of 49 healthy, low-risk volunteers resulted in successful immune responses, including cytotoxic T-cell activity. The biological response modifier MTP-PE tested in some of the participants increased their immune response but also caused significant side effects.

A number of laboratories throughout the world are attempting to develop a vaccine against the human immunodeficiency virus (HIV), the causative agent in AIDS. Animal models are being developed, but 'phase I data' about the safety of an HIV vaccine in humans has been limited. The National Institute of Allergy and Infectious Disease Acquired Immunodeficiency Syndrome Vaccine Clinical Trials Network (NIAID) has begun human trials of recombinant envelope glycoprotein 160 (rgp160), an HIV subunit vaccine. A total of 67 individuals who were healthy, HIV-negative, and at low risk for acquiring HIV, completed the study. The subjects were subdivided into four groups who received: a placebo; hepatitis B vaccine; rgp160 at 40 micrograms; or rgp160 at 80 micrograms. Injections were given at 0, 30, and 180 days; 52 of the 67 subjects received an injection again at day 540. The injections were generally well-tolerated; no significant immune function depression was seen in any of the subjects. Antibodies against HIV were detected by the Western blot assay in subjects who had received rgp160, often after the second dose, and quite frequently after the third. An issue of greater interest than antibody production is the ability of the vaccine to confer immunity against HIV, as measured by ability of the patients' sera to neutralize the virus or to induce complement immune activity. Neutralizing activity was seen in 5 of the 24 rgp160 patients and complement enhancement was observed in 6 of the 24 (3 of these subjects had both neutralizing activity and complement enhancement). It is concluded that the rgp160 HIV vaccine is safe and well-tolerated, but its efficacy at the doses studied is limited. Studies of higher doses of this vaccine are warranted. (Consumer Summary produced by Reliance Medical Information, Inc.)