title: In vivo gp41 antibodies targeting the 2F5 monoclonal antibody epitope mediate human immunodeficiency virus type 1 neutralization breadth.
abstract: The broadly neutralizing human monoclonal antibodies (MAbs) 2F5 and 4E10, both targeting the highly conserved human immunodeficiency virus type 1 (HIV-1) envelope membrane proximal external region (MPER), are among the MAbs with the broadest heterologous neutralizing activity and are of considerable interest for HIV-1 vaccine development. We have identified serum antibodies from an HIV-infected subject that both were broadly neutralizing and specifically targeted MPER epitopes that overlap the 2F5 epitope. These MPER-specific antibodies were made 15 to 20 months following transmission and concomitantly with the development of autoantibodies. Our findings suggest that multiple events (i.e., genetic predisposition and HIV-1 immune dysregulation) may be required for induction of broadly reactive gp41 MPER antibodies in natural infection.
authors.affiliation: Duke Human Vaccine Institute, Duke University Medicine Center, Durham, NC 27710, USA.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Shen
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Parks
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Kirchherr
authors.forename: Brandon F
authors.initials: BF
authors.lastname: Keele
authors.forename: Julie M
authors.initials: JM
authors.lastname: Decker
authors.forename: William A
authors.initials: WA
authors.lastname: Blattner
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Kent J
authors.initials: KJ
authors.lastname: Weinhold
authors.forename: Charles B
authors.initials: CB
authors.lastname: Hicks
authors.forename: Michael L
authors.initials: ML
authors.lastname: Greenberg
authors.forename: Beatrice H
authors.initials: BH
authors.lastname: Hahn
authors.forename: George M
authors.initials: GM
authors.lastname: Shaw
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D005260:Female; D015483:HIV Antibodies / Q000097:blood* / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D000939:Epitopes; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; C514787:gp41 protein, Human immunodeficiency virus 1