Literature DB >> 7913731

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 Belshe1, B S Graham, M C Keefer, G J Gorse, P Wright, R Dolin, T Matthews, K Weinhold, D P Bolognesi, R Sposto.   

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.

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Year:  1994        PMID: 7913731     DOI: 10.1001/jama.272.6.475

Source DB:  PubMed          Journal:  JAMA        ISSN: 0098-7484            Impact factor:   56.272


  38 in total

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2.  The role of the third beta strand in gp120 conformation and neutralization sensitivity of the HIV-1 primary isolate DH012.

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3.  A human immunodeficiency virus prime-boost immunization regimen in humans induces antibodies that show interclade cross-reactivity and neutralize several X4-, R5-, and dualtropic clade B and C primary isolates.

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9.  Genetic signatures in the envelope glycoproteins of HIV-1 that associate with broadly neutralizing antibodies.

Authors:  S Gnanakaran; Marcus G Daniels; Tanmoy Bhattacharya; Alan S Lapedes; Anurag Sethi; Ming Li; Haili Tang; Kelli Greene; Hongmei Gao; Barton F Haynes; Myron S Cohen; George M Shaw; Michael S Seaman; Amit Kumar; Feng Gao; David C Montefiori; Bette Korber
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Review 10.  Progress on the induction of neutralizing antibodies against HIV type 1 (HIV-1).

Authors:  Michael Vaine; Shan Lu; Shixia Wang
Journal:  BioDrugs       Date:  2009       Impact factor: 5.807

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