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Antibody Lineages with Vaccine-Induced Antigen-Binding Hotspots Develop Broad HIV Neutralization.
Kong, Rui; Duan, Hongying; Sheng, Zizhang; Xu, Kai; Acharya, Priyamvada; Chen, Xuejun; Cheng, Cheng; Dingens, Adam S; Gorman, Jason; Sastry, Mallika; Shen, Chen-Hsiang; Zhang, Baoshan; Zhou, Tongqing; Chuang, Gwo-Yu; Chao, Cara W; Gu, Ying; Jafari, Alexander J; Louder, Mark K; O'Dell, Sijy; Rowshan, Ariana P; Viox, Elise G; Wang, Yiran; Choi, Chang W; Corcoran, Martin M; Corrigan, Angela R; Dandey, Venkata P; Eng, Edward T; Geng, Hui; Foulds, Kathryn E; Guo, Yicheng; Kwon, Young D; Lin, Bob; Liu, Kevin; Mason, Rosemarie D; Nason, Martha C; Ohr, Tiffany Y; Ou, Li; Rawi, Reda; Sarfo, Edward K; Schön, Arne; Todd, John P; Wang, Shuishu; Wei, Hui; Wu, Winston; Mullikin, James C; Bailer, Robert T; Doria-Rose, Nicole A; Karlsson Hedestam, Gunilla B; Scorpio, Diana G; Overbaugh, Julie.
Affiliation
  • Kong R; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Duan H; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Sheng Z; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA.
  • Xu K; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Acharya P; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA; National Resource for Automated Molecular Microscopy, Simons Electron Microscopy Center, New York Structural Biology Center, New York, NY 10027, USA; Duke Human Vaccine Institute, Duke Unive
  • Chen X; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Cheng C; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Dingens AS; Basic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98195, USA; Molecular and Cellular Biology PhD Program, University of Washington, Seattle, WA 98195, USA; Division of Human Biology and Epidemiology Program, Seattle, WA 98195, USA.
  • Gorman J; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA; National Resource for Automated Molecular Microscopy, Simons Electron Microscopy Center, New York Structural Biology Center, New York, NY 10027, USA.
  • Sastry M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Shen CH; 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.
  • Zhou T; 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.
  • Chao CW; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Gu Y; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Jafari AJ; 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.
  • O'Dell S; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Rowshan AP; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Viox EG; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Wang Y; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Choi CW; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Corcoran MM; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm 17177, Sweden.
  • Corrigan AR; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Dandey VP; National Resource for Automated Molecular Microscopy, Simons Electron Microscopy Center, New York Structural Biology Center, New York, NY 10027, USA.
  • Eng ET; National Resource for Automated Molecular Microscopy, Simons Electron Microscopy Center, New York Structural Biology Center, New York, NY 10027, USA.
  • Geng H; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Foulds KE; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Guo Y; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA.
  • Kwon YD; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Lin B; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Liu K; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Mason RD; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Nason MC; Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Ohr TY; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Ou L; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Rawi R; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Sarfo EK; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Schön A; Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Todd JP; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Wang S; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Wei H; National Resource for Automated Molecular Microscopy, Simons Electron Microscopy Center, New York Structural Biology Center, New York, NY 10027, USA.
  • Wu W; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Mullikin JC; NIH Intramural Sequencing Center, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
  • Bailer RT; Vaccine Research Center, 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.
  • Karlsson Hedestam GB; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm 17177, Sweden.
  • Scorpio DG; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Overbaugh J; Division of Human Biology and Epidemiology Program, Seattle, WA 98195, USA.
Cell ; 178(3): 567-584.e19, 2019 07 25.
Article in En | MEDLINE | ID: mdl-31348886
ABSTRACT
The vaccine-mediated elicitation of antibodies (Abs) capable of neutralizing diverse HIV-1 strains has been a long-standing goal. To understand how broadly neutralizing antibodies (bNAbs) can be elicited, we identified, characterized, and tracked five neutralizing Ab lineages targeting the HIV-1-fusion peptide (FP) in vaccinated macaques over time. Genetic and structural analyses revealed two of these lineages to belong to a reproducible class capable of neutralizing up to 59% of 208 diverse viral strains. B cell analysis indicated each of the five lineages to have been initiated and expanded by FP-carrier priming, with envelope (Env)-trimer boosts inducing cross-reactive neutralization. These Abs had binding-energy hotspots focused on FP, whereas several FP-directed Abs induced by immunization with Env trimer-only were less FP-focused and less broadly neutralizing. Priming with a conserved subregion, such as FP, can thus induce Abs with binding-energy hotspots coincident with the target subregion and capable of broad neutralization.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Peptides / HIV Antibodies / AIDS Vaccines / Antibodies, Neutralizing Limits: Animals / Female / Humans / Male Language: En Journal: Cell Year: 2019 Type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Peptides / HIV Antibodies / AIDS Vaccines / Antibodies, Neutralizing Limits: Animals / Female / Humans / Male Language: En Journal: Cell Year: 2019 Type: Article Affiliation country: United States