title: Cardiolipin polyspecific autoreactivity in two broadly neutralizing HIV-1 antibodies.
abstract: The design of a human immunodeficiency virus-1 (HIV-1) immunogen that can induce broadly reactive neutralizing antibodies is a major goal of HIV-1 vaccine development. Although rare human monoclonal antibodies (mAbs) exist that broadly neutralize HIV-1, HIV-1 envelope immunogens do not induce these antibody specificities. Here we demonstrate that the two most broadly reactive HIV-1 envelope gp41 human mAbs, 2F5 and 4E10, are polyspecific autoantibodies reactive with the phospholipid cardiolipin. Thus, current HIV-1 vaccines may not induce these types of antibodies because of autoantigen mimicry of the conserved membrane-proximal epitopes of the virus. These results may have important implications for generating effective neutralizing antibody responses by using HIV-1 vaccines.
authors.affiliation: Duke University School of Medicine, Durham, NC 27710, USA. hayne002@mc.duke.edu
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
authors.forename: Judith
authors.initials: J
authors.lastname: Fleming
authors.forename: E William
authors.initials: EW
authors.lastname: St Clair
authors.forename: Herman
authors.initials: H
authors.lastname: Katinger
authors.forename: Gabriela
authors.initials: G
authors.lastname: Stiegler
authors.forename: Renate
authors.initials: R
authors.lastname: Kunert
authors.forename: James
authors.initials: J
authors.lastname: Robinson
authors.forename: Richard M
authors.initials: RM
authors.lastname: Scearce
authors.forename: Kelly
authors.initials: K
authors.lastname: Plonk
authors.forename: Herman F
authors.initials: HF
authors.lastname: Staats
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Ortel
authors.forename: Hua-Xin
authors.initials: HX
authors.lastname: Liao
authors.forename: S Munir
authors.initials: SM
authors.lastname: Alam
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D001323:Autoantibodies / Q000737:chemistry / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology; D002308:Cardiolipins / Q000276:immunology*; D045744:Cell Line, Tumor; D000939:Epitopes; D015483:HIV Antibodies / Q000737:chemistry / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D051379:Mice; D018716:Molecular Mimicry; D009500:Neutralization Tests
chemical_list: D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D001324:Autoantigens; D002308:Cardiolipins; D000939:Epitopes; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41