title: Comparison of the antibody repertoire generated in healthy volunteers following immunization with a monomeric recombinant gp120 construct derived from a CCR5/CXCR4-using human immunodeficiency virus type 1 isolate with sera from naturally infected individuals.
abstract: We have characterized sera from healthy volunteers immunized with a monomeric recombinant gp120 (rgp120) derived from a CCR5/CXCR4 (R5X4)-using subtype B isolate of human immunodeficiency virus type (HIV-1), HIV-1W61D, in comparison to sera from long-term HIV-1-infected individuals, using homologous reagents. Sera from vaccinees and HIV-1 positive subjects had similar binding titers to native monomeric rgp120W61D and showed a similar titer of antibodies inhibiting the binding of soluble CD4 (sCD4) to rgp120W61D. However, extensive peptide binding studies showed that the overall pattern of recognition of vaccinee and HIV-1-positive sera is different, with vaccinee sera displaying a wider and more potent recognition of linear V1/V2 and V3 domain epitopes. Neutralization of homologous HIV-1W61D or heterologous HIV-1M2424/4 peripheral blood mononuclear cell (PBMC)-derived virus lines by vaccinee sera could be achieved, but only after adaptation of the viruses to T-cell lines and was quickly lost on readaptation to growth in PBMC. Sera from HIV-positive individuals were able to neutralize both PBMC-grown and T-cell line-adapted viruses. Interestingly, rgp120W61D was recognized by monoclonal antibodies previously shown to neutralize primary HIV-1 isolates. The use of very potent adjuvants and R5X4 rgp120 led to an antibody response equivalent in binding activity and inhibition of binding of sCD4 to gp120 to that of HIV-positive individuals but did not lead to the induction of antibodies capable of neutralizing PBMC-grown virus.
authors.affiliation: Department of GU Medicine and Communicable Diseases, Imperial College School of Medicine at St. Mary's, London W2 1PG, United Kingdom.
authors.forename: S
authors.initials: S
authors.lastname: Beddows
authors.forename: S
authors.initials: S
authors.lastname: Lister
authors.forename: R
authors.initials: R
authors.lastname: Cheingsong
authors.forename: C
authors.initials: C
authors.lastname: Bruck
authors.forename: J
authors.initials: J
authors.lastname: Weber
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D001483:Base Sequence; D002461:Cell Line, Transformed; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015658:HIV Infections / Q000097:blood / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D014407:Tumor Cells, Cultured; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology*; D014838:Volunteers
chemical_list: D016915:AIDS Vaccines; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D014614:Vaccines, Synthetic