title: Broad and potent neutralization of HIV-1 by a gp41-specific human antibody.
abstract: Characterization of human monoclonal antibodies is providing considerable insight into mechanisms of broad HIV-1 neutralization. Here we report an HIV-1 gp41 membrane-proximal external region (MPER)-specific antibody, named 10E8, which neutralizes ∼98% of tested viruses. An analysis of sera from 78 healthy HIV-1-infected donors demonstrated that 27% contained MPER-specific antibodies and 8% contained 10E8-like specificities. In contrast to other neutralizing MPER antibodies, 10E8 did not bind phospholipids, was not autoreactive, and bound cell-surface envelope. The structure of 10E8 in complex with the complete MPER revealed a site of vulnerability comprising a narrow stretch of highly conserved gp41-hydrophobic residues and a critical arginine or lysine just before the transmembrane region. Analysis of resistant HIV-1 variants confirmed the importance of these residues for neutralization. The highly conserved MPER is a target of potent, non-self-reactive neutralizing antibodies, suggesting that HIV-1 vaccines should aim to induce antibodies to this region of HIV-1 envelope glycoprotein.
authors.affiliation: HIV-Specific Immunity Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Jinghe
authors.initials: J
authors.lastname: Huang
authors.forename: Gilad
authors.initials: G
authors.lastname: Ofek
authors.forename: Leo
authors.initials: L
authors.lastname: Laub
authors.forename: Mark K
authors.initials: MK
authors.lastname: Louder
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Doria-Rose
authors.forename: Nancy S
authors.initials: NS
authors.lastname: Longo
authors.forename: Hiromi
authors.initials: H
authors.lastname: Imamichi
authors.forename: Robert T
authors.initials: RT
authors.lastname: Bailer
authors.forename: Bimal
authors.initials: B
authors.lastname: Chakrabarti
authors.forename: Shailendra K
authors.initials: SK
authors.lastname: Sharma
authors.forename: S Munir
authors.initials: SM
authors.lastname: Alam
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Yongping
authors.initials: Y
authors.lastname: Yang
authors.forename: Baoshan
authors.initials: B
authors.lastname: Zhang
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Migueles
authors.forename: Richard
authors.initials: R
authors.lastname: Wyatt
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
authors.forename: Peter D
authors.initials: PD
authors.lastname: Kwong
authors.forename: John R
authors.initials: JR
authors.lastname: Mascola
authors.forename: Mark
authors.initials: M
authors.lastname: Connors
mesh_terms: D019943:Amino Acid Substitution; D057134:Antibodies, Neutralizing / Q000737:chemistry / Q000378:metabolism*; D000918:Antibody Specificity; D002478:Cells, Cultured; D057809:HEK293 Cells; D015483:HIV Antibodies / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000276:immunology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary
chemical_list: D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41