title: Relevance of the antibody response against human immunodeficiency virus type 1 envelope to vaccine design.
abstract: Understanding the antibody response in HIV-1 infection is important to vaccine design. We have studied the antibody response to HIV-1 envelope at the molecular level and determined the characteristics of neutralizing and non-neutralizing antibodies. These antibodies were isolated from phage display libraries prepared from long-term seropositive asymptomatic individuals. The HIV-1 envelope is presented to the immune system in several antigenically distinct configurations: unprocessed gp160, gp120 and gp41 subunits and native envelope, each of which may be important in eliciting an antibody response in HIV-1 infection. The antibodies tested characteristically had poor affinities for native envelope as expressed on the surface of virions or infected cells, but had high affinities against non-native forms of HIV-1 envelope (viral debris). An exceptionally potent neutralizing antibody in contrast, bound native envelope with equivalent or somewhat higher affinity than this. This indicates that the antibody response in HIV-1 infection is principally elicited by viral debris rather than virions, and that these antibodies bind and neutralize viruses sub-optimally. Potential vaccines should be designed to elicit responses against native envelope.
authors.affiliation: Department of Immunology, Scripps Research Institute, La Jolla, CA 92037, USA. parren@scripps.edu
authors.forename: P W
authors.initials: PW
authors.lastname: Parren
authors.forename: M C
authors.initials: MC
authors.lastname: Gauduin
authors.forename: R A
authors.initials: RA
authors.lastname: Koup
authors.forename: P
authors.initials: P
authors.lastname: Poignard
authors.forename: P
authors.initials: P
authors.lastname: Fisicaro
authors.forename: D R
authors.initials: DR
authors.lastname: Burton
authors.forename: Q J
authors.initials: QJ
authors.lastname: Sattentau
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D015195:Drug Design; D015686:Gene Products, env / Q000276:immunology*; D015483:HIV Antibodies / Q000276:immunology*; D015488:HIV Antigens / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D019302:HIV Envelope Protein gp160 / Q000276:immunology; D015700:HIV Envelope Protein gp41 / Q000276:immunology; D015658:HIV Infections / Q000517:prevention & control; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D009500:Neutralization Tests; D014771:Virion / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D015686:Gene Products, env; D015483:HIV Antibodies; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D015700:HIV Envelope Protein gp41