Structural prerequisites for intersubtype B and D antigenicity of the third variable envelope region (V3) of human immunodeficiency virus type 1

To elucidate the structural requirements for intersubtype antigenicity of h uman immunodeficiency virus type 1 (HIV-1) third variable envelope region ( V3), synthetic peptides were used in enzyme immunoassays (EIAs) with serum samples from persons with proven or probable subtype B and D infections. Ma thematical analyses of results from EIAs with singly substituted V3 peptide s revealed important residues determining overall N-terminal V3 peptide ant igenicity, This information was used to design V3 immunogens, rabbit antise rum to which were tested in EIA and for in vitro neutralization of molecula r clones of HIV-1(MN) and HIV-1(MAL). Intersubtype-reactive epitopes were d istributed toward the N-terminal half of the V3 loop. Lysine at: position 3 10, arginine at position 311, and isoleucine at position 314, all derived f rom the MN primary sequence, were major determinants of intersubtype V3 ant igenicity, Combinations of residues that enhanced antigenicity often contai ned lysine at position 310. Threonine at position 308 was common in the lea st advantageous combinations. V3 immunogens modified to achieve optimal ant igenicity induced antiserum with augmented cross-neutralization of virus fr om MAL and MN molecular clones, suggesting one approach to subunit vaccine development.