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
R. B. Belshe, B. S. Graham, M. C. Keefer, G. J. Gorse, P. Wright, R. Dolin, T. Matthews, K. Weinhold, D. P. Bolognesi, R. Sposto and al. et
Department of Medicine, St Louis University School of Medicine, MO 63104.
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.
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Neutralizing Antibodies in Sera from Macaques Infected with Chimeric Simian-Human Immunodeficiency Virus Containing the Envelope Glycoproteins of either a Laboratory-Adapted Variant or a Primary Isolate of Human Immunodeficiency Virus Type 1
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Immunological and Virological Analyses of Persons Infected by Human Immunodeficiency Virus Type 1 while Participating in Trials of Recombinant gp120 Subunit Vaccines
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The role of the third beta strand in gp120 conformation and neutralization sensitivity of the HIV-1 primary isolate DH012
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