Soto, M.J. (María José)

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    Induction of neutralizing antibodies against human immunodeficiency virus type 1 using synthetic peptide constructs containing an immunodominant T-helper cell determinant from vpr
    (Raven Press, 1994) Labarga, P. (Pablo); Borras-Cuesta, F. (Francisco); Prieto, J. (Jesús); Prieto, I. (Isidro); Sarobe, P. (Pablo); Golvano, J.J. (José Javier); Soto, M.J. (María José); Gullon, A. (Arturo); Lasarte, J.J. (Juan José)
    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.