title: In vitro antigen challenge of human antibody libraries for vaccine evaluation: the human immunodeficiency virus type 1 envelope.
abstract: Human antibody responses, or versions thereof, can be cloned as phage display libraries. In vaccine evaluation, the possibility therefore exists of challenging the human response in vitro, rather than in vivo, in order to assist in establishing the most promising vaccine leads. The characteristics of the antibodies retrieved directly indicate the strengths and weaknesses of the vaccine at the molecular level. We applied this approach to compare recombinant and native human immunodeficiency virus type 1 envelope preparations. We conclude that recombinant gp160, gp140, and, to a lesser extent, gp120 present epitopes around the CD4 binding site in a conformation different from that of the native multimer and contrary to expected vaccine requirements. Antibodies to the potently neutralizing b12 epitope were selected preferentially from an immune library by purified human immunodeficiency virus type 1 virions. This suggests that b12 is a major epitope on the virions, in contrast to recombinant envelope preparations, in which related, weakly neutralizing epitopes predominate. Although the majority of virions in the preparation used are expected to be noninfective, it appears that they predominantly express a native envelope configuration and would be able to elicit potent neutralizing antibodies.
authors.affiliation: Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: P W
authors.initials: PW
authors.lastname: Parren
authors.forename: P
authors.initials: P
authors.lastname: Fisicaro
authors.forename: A F
authors.initials: AF
authors.lastname: Labrijn
authors.forename: J M
authors.initials: JM
authors.lastname: Binley
authors.forename: W P
authors.initials: WP
authors.lastname: Yang
authors.forename: H J
authors.initials: HJ
authors.lastname: Ditzel
authors.forename: C F
authors.initials: CF
authors.lastname: Barbas
authors.forename: D R
authors.initials: DR
authors.lastname: Burton
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004341:Drug Evaluation; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015686:Gene Products, env / Q000276:immunology*; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D019302:HIV Envelope Protein gp160 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology*; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D014407:Tumor Cells, Cultured; D014614:Vaccines, Synthetic / Q000276:immunology*; D054299:env Gene Products, Human Immunodeficiency Virus
chemical_list: D016915:AIDS Vaccines; D018984:Epitopes, T-Lymphocyte; D015686:Gene Products, env; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D007140:Immunoglobulin Fab Fragments; D014614:Vaccines, Synthetic; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1