Neutralizing Antibodies to HIV-1 in Seronegative Volunteers Immunized With Recombinant gp 120 From the MN Strain of HIV-1

Abstract

Objective. —To evaluate the safety and immunogenicity of the MN strain of recombinant gp 120 (MN rgp 120) as a vaccine prototype to prevent human immunodeficiency virus (HIV). Design. —Double-blind, randomized, placebo-controlled study with subjects vaccinated at 0, 4, 24, and 48 weeks and followed up through 64 weeks. Setting. —The AIDS Vaccine Evaluation Units in St Louis, Mo, Nashville, Tenn, and Rochester, NY, conducted the clinical study. Laboratory studies were conducted at Duke University, Raleigh, NC; data analysis was done by the Data Coordinating and Analysis Center at the EMMES Corporation, Potomac, Md. Participants. —Fifty-seven persons seronegative for HIV, at low risk for acquiring HIV infection, and 18 to 60 years of age. Interventions. —The MN rgp 120 vaccine was administered to 12 volunteers each in doses of 100 μg, 300 μg, or 600 μg, and 12 volunteers received a combination of 300 μg of MN rgp 120 vaccine and 300 μg of vaccine from rgp 120 of strain IIIB. Nine volunteers received alum adjuvant alone (control). Main Outcome Measures. —Safety was assessed by monitoring lymphocyte subsets, serum creatinine, and liver enzymes. Immunogenicity was measured by enzyme-linked immunosorbent assay using the immunogen and synthetic peptide corresponding to the variable region 3 domain of gp 120. Functional antibody assays included CD4 binding blocking; antibody-dependent, cell-mediated cytotoxicity; and neutralization of homologous and heterologous HIV strains. Results. —No severe adverse reactions occurred. In 33 of 48 volunteers, tw doses of vaccine induced antibodies that neutralized the homologous strain HIV-1/MN. Three doses of vaccine induced antibodies that neutralized MN (in 46 of 48 volunteers), SF-2 (in 45 of 48 volunteers), or IIIB strains of HIV-1 (in 30 of 48 volunteers). Conclusion. —The vaccines were safe and immunogenic. Multiple injections of vaccine broadened and increased the neutralizing antibody response. ( JAMA . 1994;272:475-480)