title: Immunogenicity of full length and truncated forms of the human immunodeficiency virus type I envelope glycoprotein.
abstract: We have monitored the immunogenicity of a V1V2 sub-fragment of gp 120 in contrast to the full length protein and to a truncated form (PR12) where the V1, V2 and V3 regions were removed. In contrast to previously published work [1] these studies show that monomeric forms of envelope are capable of inducing antibodies specific for both linear and discontinuous epitopes. These antibodies are capable of neutralising HIV infectivity. The majority of neutralising antibodies were specific for epitopes within the V2 and V3 regions demonstrating the immunodominance of these regions in monomeric gp 120. Relatively few of the antibodies were specific for the CD4 binding site, suggesting that this region is poorly immunogenic. Immunisation of rats with the PR12 truncated protein did not significantly enhance the immunogenicity of the CD4 binding site. However, the immune response generated included antibodies capable of binding to diverse primary HIV-1 and HIV-2 envelope glycoproteins. We have shown that up to 30% of sera from HIV-1 infected individuals have antibodies that are capable of recognising conformation-dependent 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 antibodies to this region contribute to the cross-reactive neutralising response.
authors.affiliation: University of Reading, School of Animal and Microbial Sciences, Whiteknights, UK.
authors.forename: J A
authors.initials: JA
authors.lastname: McKeating
authors.forename: C
authors.initials: C
authors.lastname: Shotton
authors.forename: S
authors.initials: S
authors.lastname: Jeffs
authors.forename: C
authors.initials: C
authors.lastname: Palmer
authors.forename: A
authors.initials: A
authors.lastname: Hammond
authors.forename: J
authors.initials: J
authors.lastname: Lewis
authors.forename: K
authors.initials: K
authors.lastname: Oliver
authors.forename: J
authors.initials: J
authors.lastname: May
authors.forename: P
authors.initials: P
authors.lastname: Balfe
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology; D000818:Animals; D000939:Epitopes / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000276:immunology*; D051381:Rats
chemical_list: D016915:AIDS Vaccines; D000939:Epitopes; D015699:HIV Envelope Protein gp120; D010446:Peptide Fragments