Induction of neutralizing antibodies against human immunodeficiency virus type 1 using synthetic peptide constructs containing an immunodominant T-helper cell determinant from vpr
Keywords: 
Gene Products, vpr/immunology
HIV Antibodies/biosynthesis
HIV-1/immunology
Immunodominant Epitopes/immunology
T-Lymphocytes, Helper-Inducer/immunology
Issue Date: 
1994
Publisher: 
Raven Press
ISSN: 
0894-9255
Citation: 
Sarobe P, Lasarte JJ, Golvano JJ, Prieto I, Gullon A, Soto MJ, et al. Induction of neutralizing antibodies against human immunodeficiency virus type 1 using synthetic peptide constructs containing an immunodominant T-helper cell determinant from vpr. J Acquir Immune Defic Syndr 1994 Jul;7(7):635-640.
Abstract
Identification of immunodominant T-helper-cell determinants after natural infection is an important step in the design of immunogens for potential use in vaccination. Using cells from human immunodeficiency virus type 1 (HIV-1)-infected individuals and a panel of peptides encompassing the sequence of the regulatory protein vpr from HIV-1, we identified the T-helper determinant QLLFIHFRIGCRHSR, which is active in 37.5% of these individuals. To gain insight on the efficacy of this peptide in helping induce neutralizing antibodies against a B-cell determinant (BD), we synthesized constructs containing B- and T-cell determinants and tested them in BALB/c mice, the highest responders to the T-cell determinant moiety among several strains tested. These immunogens induced antibodies against two chosen B-cell determinants from HIV-1IIIB gp160 (amino acids 310-322 from the V3 loop of gp120 and 736-751 from gp41) that were able to neutralize HIV-1 infection in vitro. The highest neutralization titer against HIV-1IIIB was obtained by immunization with the homopolymer of the construct containing the T-cell epitope from vpr and the B-cell epitope from the V3 loop. We believe that the immunodominant T-cell determinant from vpr is a promising epitope to consider in the design of future peptide vaccines.

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