IMMUNOGENICITY OF FULL-LENGTH AND TRUNCATED FORMS OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-I ENVELOPE GLYCOPROTEIN

We have monitored the immunogenicity of a V1V2 sub-fragment of gp120 i n contrast to the full length protein and to a truncated form (PR12) w here the V1, V2 and V3 regions were removed. In contrast to previously published work [1] these studies show that monomeric forms of envelop e are capable of inducing antibodies specific for both linear and disc ontinuous epitopes. These antibodies are capable of neutralising HIV i nfectivity. The majority of neutralising antibodies were specific for epitopes within the V2 and V3 regions demonstrating the immunodominanc e of these regions in monomeric gp120. Relatively few of the antibodie s were specific for the CD4 binding site, suggesting that this region is poorly immunogenic. Immunisation of rats with the PR12 truncated pr otein did not significantly enhance the immunogenicity of the CD4 bind ing site. However, the immune response generated included antibodies c apable of binding to diverse primary HIV-I and HIV-2 envelope glycopro teins. We have shown that up to 30% of sera from HIV-1 infected indivi duals have antibodies that are capable of recognising conformation-dep endent epitopes within the V1V2 region of the clone HXB10, suggesting the presence of conserved cross-reactive epitopes. Furthermore we have shown an association between the presence of V1V2 reactive antibodies and the neutralisation titre of the sera tested suggesting that antib odies to this region contribute to the cross-reactive neutralising res ponse.