Document 0724
 DOCN  M9480724
 TI    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 [see comments]
 DT    9410
 AU    Belshe RB; Graham BS; Keefer MC; Gorse GJ; Wright P; Dolin R; Matthews
       T; Weinhold K; Bolognesi DP; Sposto R; et al; Department of Medicine, St
       Louis University School of Medicine,; MO 63104.
 SO    JAMA. 1994 Aug 10;272(6):475-80. Unique Identifier : AIDSLINE
       MED/94315727
 CM    Comment in: JAMA 1994 Aug 10;272(6):488-9
 AB    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.
 DE    Adult  Aged  Antibody Affinity  AIDS Vaccines/ADMINISTRATION &
       DOSAGE/*IMMUNOLOGY/PHARMACOLOGY  Dose-Response Relationship, Immunologic
       Double-Blind Method  Human  HIV Antibodies/*IMMUNOLOGY  HIV Envelope
       Protein gp120/ADMINISTRATION & DOSAGE/*IMMUNOLOGY/  PHARMACOLOGY  HIV
       Infections/*PREVENTION & CONTROL  HIV Seronegativity/*IMMUNOLOGY
       HIV-1/*IMMUNOLOGY  Leukocyte Count  Middle Age  Neutralization Tests
       Peptide Fragments  Recombinant Proteins/IMMUNOLOGY/PHARMACOLOGY
       Support, U.S. Gov't, P.H.S.  T4 Lymphocytes  *Vaccination  CLINICAL
       TRIAL  JOURNAL ARTICLE  RANDOMIZED CONTROLLED TRIAL

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).