Your browser doesn't support javascript.
loading
Identification of a CD4-Binding-Site Antibody to HIV that Evolved Near-Pan Neutralization Breadth.
Huang, Jinghe; Kang, Byong H; Ishida, Elise; Zhou, Tongqing; Griesman, Trevor; Sheng, Zizhang; Wu, Fan; Doria-Rose, Nicole A; Zhang, Baoshan; McKee, Krisha; O'Dell, Sijy; Chuang, Gwo-Yu; Druz, Aliaksandr; Georgiev, Ivelin S; Schramm, Chaim A; Zheng, Anqi; Joyce, M Gordon; Asokan, Mangaiarkarasi; Ransier, Amy; Darko, Sam; Migueles, Stephen A; Bailer, Robert T; Louder, Mark K; Alam, S Munir; Parks, Robert; Kelsoe, Garnett; Von Holle, Tarra; Haynes, Barton F; Douek, Daniel C; Hirsch, Vanessa; Seaman, Michael S; Shapiro, Lawrence; Mascola, John R; Kwong, Peter D; Connors, Mark.
Affiliation
  • Huang J; HIV-Specific Immunity Section of the Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Kang BH; HIV-Specific Immunity Section of the Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Ishida E; HIV-Specific Immunity Section of the Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Zhou T; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Griesman T; HIV-Specific Immunity Section of the Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Sheng Z; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
  • Wu F; Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Doria-Rose NA; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Zhang B; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • McKee K; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • O'Dell S; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Chuang GY; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Druz A; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Georgiev IS; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Schramm CA; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
  • Zheng A; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Joyce MG; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Asokan M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Ransier A; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Darko S; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Migueles SA; HIV-Specific Immunity Section of the Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Bailer RT; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Louder MK; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Alam SM; Duke Human Vaccine Institute, Duke University, Durham, NC 27710, USA.
  • Parks R; Duke Human Vaccine Institute, Duke University, Durham, NC 27710, USA.
  • Kelsoe G; Duke Human Vaccine Institute, Duke University, Durham, NC 27710, USA.
  • Von Holle T; Duke Human Vaccine Institute, Duke University, Durham, NC 27710, USA.
  • Haynes BF; Duke Human Vaccine Institute, Duke University, Durham, NC 27710, USA.
  • Douek DC; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Hirsch V; Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Seaman MS; Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
  • Shapiro L; 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.
  • Mascola JR; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Kwong PD; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Connors M; 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.
Immunity ; 45(5): 1108-1121, 2016 11 15.
Article in En | MEDLINE | ID: mdl-27851912
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.
Subject(s)
Key words

Full text: 1 Database: MEDLINE Main subject: Binding Sites, Antibody / HIV Antibodies / HIV Infections / HIV-1 / Antibodies, Neutralizing Type of study: Diagnostic_studies Limits: Humans Language: En Year: 2016 Type: Article

Full text: 1 Database: MEDLINE Main subject: Binding Sites, Antibody / HIV Antibodies / HIV Infections / HIV-1 / Antibodies, Neutralizing Type of study: Diagnostic_studies Limits: Humans Language: En Year: 2016 Type: Article