Neutralizing antibodies to HIV-1 in seronegative volunteers immunized with recombinant gp120 from the MN strain of HIV-1. NIAID AIDS Vaccine Clinical Trials Network.

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.