EFFECT OF SIALIC-ACID REMOVAL ON THE ANTIBODY-RESPONSE TO THE 3RD VARIABLE DOMAIN OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENVELOPE GLYCOPROTEIN

The gp160 envelope glycoprotein of human immunodeficiency virus type-1 (HIV-1) is an essential component of current vaccine trials. The glyc ans of gp160, part of which are highly sialylated, have been shown to influence gp160 immunogenicity. Here, using a panel of synthetic V3 pe ptides,awn characterized the anti-V3 antibodies generated in rabbits i mmunized by desialylated recombinant gp160LAI. Amino acid residues fla nking the GPGR tip of V3 were necessary for the recognition by anti-V3 antibodies raised against either the native or desialylated gp160. Bo th types of antibodies reacted to V3 peptides of MN and SF2 strains an d with a North American/European V3 consensus peptide, while anti-desi alylated gp160LAI antibodies reacted in addition to the V3 of CDC4, WM J2 and NY5 strains. Yet, the V3 peptides did not significantly differ in their secondary structure, as determined by circular dichroism. The titer and avidity for V3MN of anti-desialylated gp160LAI antibodies w ere significantly lower than those of anti-native gp160LAI which likel y accounts for the inability of anti-desialylated gp160LAI sera to neu tralize HIV-1MN-induced syncytia. These results indicate that V3 immun ogenicity may be influenced by subtle directed changes in the gp160 gl ycosylation pattern.