Abstract

OBJECTIVE:

To evaluate the safety and immunogenicity of the MN strain of recombinant gp120 (MN rgp120) 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 rgp120 vaccine was administered to 12 volunteers each in doses of 100 micrograms, 300 micrograms, or 600 micrograms, and 12 volunteers received a combination of 300 micrograms of MN rgp120 vaccine and 300 micrograms of vaccine from rgp120 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 gp120. 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, two 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.