title: Identification of a CD4-Binding-Site Antibody to HIV that Evolved Near-Pan Neutralization Breadth.
abstract: Detailed studies of the broadly neutralizing antibodies (bNAbs) that underlie the best available examples of the humoral immune response to HIV are providing important information for the development of therapies and prophylaxis for HIV-1 infection. Here, we report a CD4-binding site (CD4bs) antibody, named N6, that potently neutralized 98% of HIV-1 isolates, including 16 of 20 that were resistant to other members of its class. N6 evolved a mode of recognition such that its binding was not impacted by the loss of individual contacts across the immunoglobulin heavy chain. In addition, structural analysis revealed that the orientation of N6 permitted it to avoid steric clashes with glycans, which is a common mechanism of resistance. Thus, an HIV-1-specific bNAb can achieve potent, near-pan neutralization of HIV-1, making it an attractive candidate for use in therapy and prophylaxis.
authors.affiliation: HIV-Specific Immunity Section of the Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Jinghe
authors.initials: J
authors.lastname: Huang
authors.affiliation: HIV-Specific Immunity Section of the Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Byong H
authors.initials: BH
authors.lastname: Kang
authors.affiliation: HIV-Specific Immunity Section of the Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Elise
authors.initials: E
authors.lastname: Ishida
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Tongqing
authors.initials: T
authors.lastname: Zhou
authors.affiliation: HIV-Specific Immunity Section of the Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Trevor
authors.initials: T
authors.lastname: Griesman
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
authors.forename: Zizhang
authors.initials: Z
authors.lastname: Sheng
authors.affiliation: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Fan
authors.initials: F
authors.lastname: Wu
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Doria-Rose
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Baoshan
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Krisha
authors.initials: K
authors.lastname: McKee
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Sijy
authors.initials: S
authors.lastname: O'Dell
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Gwo-Yu
authors.initials: GY
authors.lastname: Chuang
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Aliaksandr
authors.initials: A
authors.lastname: Druz
authors.affiliation: Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: Ivelin S
authors.initials: IS
authors.lastname: Georgiev
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
authors.forename: Chaim A
authors.initials: CA
authors.lastname: Schramm
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Anqi
authors.initials: A
authors.lastname: Zheng
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: M Gordon
authors.initials: MG
authors.lastname: Joyce
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Mangaiarkarasi
authors.initials: M
authors.lastname: Asokan
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Ransier
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Sam
authors.initials: S
authors.lastname: Darko
authors.affiliation: HIV-Specific Immunity Section of the Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Migueles
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Bailer
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Mark K
authors.initials: MK
authors.lastname: Louder
authors.affiliation: Duke Human Vaccine Institute, Duke University, Durham, NC 27710, USA.
authors.forename: S Munir
authors.initials: SM
authors.lastname: Alam
authors.affiliation: Duke Human Vaccine Institute, Duke University, Durham, NC 27710, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Parks
authors.affiliation: Duke Human Vaccine Institute, Duke University, Durham, NC 27710, USA.
authors.forename: Garnett
authors.initials: G
authors.lastname: Kelsoe
authors.affiliation: Duke Human Vaccine Institute, Duke University, Durham, NC 27710, USA.
authors.forename: Tarra
authors.initials: T
authors.lastname: Von Holle
authors.affiliation: Duke Human Vaccine Institute, Duke University, Durham, NC 27710, USA.
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Douek
authors.affiliation: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Hirsch
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Seaman
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Shapiro
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Mascola
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Kwong
authors.affiliation: HIV-Specific Immunity Section of the Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA. Electronic address: mconnors@nih.gov.
authors.forename: Mark
authors.initials: M
authors.lastname: Connors
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology*; D000918:Antibody Specificity; D001666:Binding Sites, Antibody / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002469:Cell Separation; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans
chemical_list: D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120
keywords: CD4-binding site; HIV; antibody; envelope; immunotherapy; neutralizing; prophylaxis; resistance; structure; vaccine