title: Native but not denatured recombinant human immunodeficiency virus type 1 gp120 generates broad-spectrum neutralizing antibodies in baboons.
abstract: The protection of individuals from human immunodeficiency virus type 1 (HIV-1) infection with an envelope subunit derived from a single isolate will require the presentation of conserved epitopes in gp120. The objective of the studies presented here was to test whether a native recombinant gp120 (rgp120) immunogen would elicit responses to conserved neutralization epitopes that are not present in a denatured recombinant gp120 antigen from the same virus isolate. In a large study of 51 baboons, we have generated heterologous neutralizing activity with native, glycosylated rgp120SF2 but not with denatured, nonglycosylated env 2-3SF2. After repeated exposure to rgp120SF2 formulated with one of several adjuvants, virus isolates from the United States, the Caribbean, and Africa were neutralized. The timing of the immunization regimen and the choice of adjuvant affected the virus neutralization titers both quantitatively and qualitatively. These results suggest that vaccination with native, glycosylated rgp120 from a single virus isolate, HIV-SF2, may elicit a protective immune response effective against geographically and sequentially distinct HIV-1 isolates.
authors.affiliation: Chiron Corporation, Emeryville, California 94608-2916.
authors.forename: N L
authors.initials: NL
authors.lastname: Haigwood
authors.forename: P L
authors.initials: PL
authors.lastname: Nara
authors.forename: E
authors.initials: E
authors.lastname: Brooks
authors.forename: G A
authors.initials: GA
authors.lastname: Van Nest
authors.forename: G
authors.initials: G
authors.lastname: Ott
authors.forename: K W
authors.initials: KW
authors.lastname: Higgins
authors.forename: N
authors.initials: N
authors.lastname: Dunlop
authors.forename: C J
authors.initials: CJ
authors.lastname: Scandella
authors.forename: J W
authors.initials: JW
authors.lastname: Eichberg
authors.forename: K S
authors.initials: KS
authors.lastname: Steimer
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology; D000276:Adjuvants, Immunologic; D000595:Amino Acid Sequence; D000818:Animals; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D006031:Glycosylation; D015483:HIV Antibodies / Q000096:biosynthesis*; D015488:HIV Antigens / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D007116:Immunization, Passive; D007117:Immunization, Secondary; D007700:Kinetics; D008137:Longitudinal Studies; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010215:Papio; D010446:Peptide Fragments / Q000276:immunology; D011489:Protein Denaturation; D011994:Recombinant Proteins / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D015483:HIV Antibodies; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic