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Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody.
Bonsignori, Mattia; Zhou, Tongqing; Sheng, Zizhang; Chen, Lei; Gao, Feng; Joyce, M Gordon; Ozorowski, Gabriel; Chuang, Gwo-Yu; Schramm, Chaim A; Wiehe, Kevin; Alam, S Munir; Bradley, Todd; Gladden, Morgan A; Hwang, Kwan-Ki; Iyengar, Sheelah; Kumar, Amit; Lu, Xiaozhi; Luo, Kan; Mangiapani, Michael C; Parks, Robert J; Song, Hongshuo; Acharya, Priyamvada; Bailer, Robert T; Cao, Allen; Druz, Aliaksandr; Georgiev, Ivelin S; Kwon, Young D; Louder, Mark K; Zhang, Baoshan; Zheng, Anqi; Hill, Brenna J; Kong, Rui; Soto, Cinque; Mullikin, James C; Douek, Daniel C; Montefiori, David C; Moody, Michael A; Shaw, George M; Hahn, Beatrice H; Kelsoe, Garnett; Hraber, Peter T; Korber, Bette T; Boyd, Scott D; Fire, Andrew Z; Kepler, Thomas B; Shapiro, Lawrence; Ward, Andrew B; Mascola, John R; Liao, Hua-Xin; Kwong, Peter D.
Affiliation
  • Bonsignori M; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
  • Zhou T; Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Sheng Z; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Department of Systems Biology, Columbia University, New York, NY 10032, USA.
  • Chen L; Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Gao F; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
  • Joyce MG; Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Ozorowski G; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology
  • Chuang GY; Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Schramm CA; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Department of Systems Biology, Columbia University, New York, NY 10032, USA.
  • Wiehe K; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
  • Alam SM; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
  • Bradley T; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
  • Gladden MA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
  • Hwang KK; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
  • Iyengar S; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
  • Kumar A; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
  • Lu X; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
  • Luo K; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
  • Mangiapani MC; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
  • Parks RJ; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
  • Song H; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
  • Acharya P; Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Bailer RT; Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Cao A; Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Druz A; Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Georgiev IS; Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA; Department of Electri
  • Kwon YD; Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Louder MK; Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Zhang B; Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Zheng A; Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Hill BJ; Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Kong R; Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Soto C; Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Mullikin JC; NIH Intramural Sequencing Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Douek DC; Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Montefiori DC; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA; Department of Pediatrics, Duke University School of Medicine, Durham, NC 27710, USA; Department of Immunology, Duke University Sc
  • Moody MA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Pediatrics, Duke University School of Medicine, Durham, NC 27710, USA; Department of Immunology, Duke University School of Medicine, Durham, NC 27710, USA.
  • Shaw GM; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Hahn BH; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Kelsoe G; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Immunology, Duke University School of Medicine, Durham, NC 27710, USA.
  • Hraber PT; Los Alamos National Laboratory, Los Alamos, NM 87544, USA.
  • Korber BT; Los Alamos National Laboratory, Los Alamos, NM 87544, USA.
  • Boyd SD; Department of Pathology, Stanford School of Medicine, Palo Alto, CA 94305, USA.
  • Fire AZ; Department of Pathology, Stanford School of Medicine, Palo Alto, CA 94305, USA.
  • Kepler TB; Department of Microbiology, Boston University, Boston, MA 02118, USA; Department of Mathematics and Statistics, Boston University, Boston, MA 02118, USA.
  • Shapiro L; Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Department of Systems Biology, Columbia University, New York, NY
  • Ward AB; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology
  • Mascola JR; Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Liao HX; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
  • Kwong PD; Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: pdkwong@nih.gov.
Cell ; 165(2): 449-63, 2016 Apr 07.
Article in En | MEDLINE | ID: mdl-26949186
ABSTRACT
Antibodies with ontogenies from VH1-2 or VH1-46-germline genes dominate the broadly neutralizing response against the CD4-binding site (CD4bs) on HIV-1. Here, we define with longitudinal sampling from time-of-infection the development of a VH1-46-derived antibody lineage that matured to neutralize 90% of HIV-1 isolates. Structures of lineage antibodies CH235 (week 41 from time-of-infection, 18% breadth), CH235.9 (week 152, 77%), and CH235.12 (week 323, 90%) demonstrated the maturing epitope to focus on the conformationally invariant portion of the CD4bs. Similarities between CH235 lineage and five unrelated CD4bs lineages in epitope focusing, length-of-time to develop breadth, and extraordinary level of somatic hypermutation suggested commonalities in maturation among all CD4bs antibodies. Fortunately, the required CH235-lineage hypermutation appeared substantially guided by the intrinsic mutability of the VH1-46 gene, which closely resembled VH1-2. We integrated our CH235-lineage findings with a second broadly neutralizing lineage and HIV-1 co-evolution to suggest a vaccination strategy for inducing both lineages.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: HIV Antibodies / HIV Infections / AIDS Vaccines / Antibodies, Neutralizing Type of study: Prognostic_studies Limits: Humans Language: En Journal: Cell Year: 2016 Type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: HIV Antibodies / HIV Infections / AIDS Vaccines / Antibodies, Neutralizing Type of study: Prognostic_studies Limits: Humans Language: En Journal: Cell Year: 2016 Type: Article Affiliation country: United States