Fine characterization of a V3-region neutralizing epitope in human immunodeficiency virus type 2

We have previously identified two distinct antigenic sites in the third var iable region (V3) of human immunodeficiency virus type 2 (HIV-2) correspond ing to the principal neutralizing determinant (PND) of HIV-1, the conserved Phe-His-Ser-Gln and Trp-Cys-Arg motifs (positions 315-318 and 329-331), wh ich possibly interact to form a discontinuous antigenic site. The aim of th is study was to further identify and characterize the immunogenic sites in the V3-loop of HIV-2 that are important in the binding of neutralizing anti bodies and to study in detail the importance of different configurations of peptides corresponding to this region. Peptides representing modifications of the V3-region of HIV-2(SBL6669-ISY) were used for immunization of guine a pigs. With one exception, both the Phe-His-Ser-Gln and the Trp-Cys-Arg mo tifs were required in the peptide sequences to obtain neutralizing hyperimm une guinea pig sera, and the highest titers were obtained after immunizatio n with 20-27 amino acids (aa) long peptides. Neither substitutions nor dele tions of residues between the two motifs, nor the addition of peptide seque nces representing a T-helper epitope improved the induction of neutralizing antibodies. Computer simulation modeling revealed that the Phe-315, His-31 6, Trp-329 and Cys-330 are likely to participate in the formation of a disc ontinuous epitope. Taken together, these data support the hypothesis that t he well conserved motifs FHSQ (positions 315-318) and WCR (positions 329-33 1) of the HIV-2(SBL6669) V3 region are important targets for neutralizing a ntibodies, and this may have implications for the design of a future HIV-2 vaccine. (C) 1999 Elsevier Science B.V. All rights reserved.