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

Abstract

<h3>Objective.</h3> —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). <h3>Design.</h3> —Double-blind, randomized, placebo-controlled study with subjects vaccinated at 0, 4, 24, and 48 weeks and followed up through 64 weeks. <h3>Setting.</h3> —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. <h3>Participants.</h3> —Fifty-seven persons seronegative for HIV, at low risk for acquiring HIV infection, and 18 to 60 years of age. <h3>Interventions.</h3> —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). <h3>Main Outcome Measures.</h3> —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. <h3>Results.</h3> —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). <h3>Conclusion.</h3> —The vaccines were safe and immunogenic. Multiple injections of vaccine broadened and increased the neutralizing antibody response. (<i>JAMA</i>. 1994;272:475-480)