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Structures of HIV-1 Env V1V2 with broadly neutralizing antibodies reveal commonalities that enable vaccine design.
Gorman, Jason; Soto, Cinque; Yang, Max M; Davenport, Thaddeus M; Guttman, Miklos; Bailer, Robert T; Chambers, Michael; Chuang, Gwo-Yu; DeKosky, Brandon J; Doria-Rose, Nicole A; Druz, Aliaksandr; Ernandes, Michael J; Georgiev, Ivelin S; Jarosinski, Marissa C; Joyce, M Gordon; Lemmin, Thomas M; Leung, Sherman; Louder, Mark K; McDaniel, Jonathan R; Narpala, Sandeep; Pancera, Marie; Stuckey, Jonathan; Wu, Xueling; Yang, Yongping; Zhang, Baoshan; Zhou, Tongqing; Mullikin, James C; Baxa, Ulrich; Georgiou, George; McDermott, Adrian B; Bonsignori, Mattia; Haynes, Barton F; Moore, Penny L; Morris, Lynn; Lee, Kelly K; Shapiro, Lawrence; Mascola, John R; Kwong, Peter D.
  • Gorman J; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Soto C; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Yang MM; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Davenport TM; Department of Medicinal Chemistry, University of Washington, Seattle, Washington, USA.
  • Guttman M; Department of Medicinal Chemistry, University of Washington, Seattle, Washington, USA.
  • Bailer RT; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Chambers M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Chuang GY; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • DeKosky BJ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Doria-Rose NA; Department of Chemical Engineering, University of Texas at Austin, Austin, Texas, USA.
  • Druz A; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Ernandes MJ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Georgiev IS; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Jarosinski MC; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Joyce MG; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Lemmin TM; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Leung S; Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, USA.
  • Louder MK; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • McDaniel JR; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Narpala S; Department of Chemical Engineering, University of Texas at Austin, Austin, Texas, USA.
  • Pancera M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Stuckey J; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Wu X; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Yang Y; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Zhang B; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Zhou T; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Mullikin JC; NIH Intramural Sequencing Center (NISC), National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.
  • Baxa U; NIH Intramural Sequencing Center (NISC), National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.
  • Georgiou G; Electron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
  • McDermott AB; Department of Chemical Engineering, University of Texas at Austin, Austin, Texas, USA.
  • Bonsignori M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Haynes BF; Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.
  • Moore PL; Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.
  • Morris L; Center for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.
  • Lee KK; Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
  • Shapiro L; Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Congella, South Africa.
  • Mascola JR; Center for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.
  • Kwong PD; Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Nat Struct Mol Biol ; 23(1): 81-90, 2016 Jan.
Article en En | MEDLINE | ID: mdl-26689967
ABSTRACT
Broadly neutralizing antibodies (bNAbs) against HIV-1 Env V1V2 arise in multiple donors. However, atomic-level interactions had previously been determined only with antibodies from a single donor, thus making commonalities in recognition uncertain. Here we report the cocrystal structure of V1V2 with antibody CH03 from a second donor and model Env interactions of antibody CAP256-VRC26 from a third donor. These V1V2-directed bNAbs used strand-strand interactions between a protruding antibody loop and a V1V2 strand but differed in their N-glycan recognition. Ontogeny analysis indicated that protruding loops develop early, and glycan interactions mature over time. Altogether, the multidonor information suggested that V1V2-directed bNAbs form an 'extended class', for which we engineered ontogeny-specific antigens Env trimers with chimeric V1V2s that interacted with inferred ancestor and intermediate antibodies. The ontogeny-based design of vaccine antigens described here may provide a general means for eliciting antibodies of a desired class.
Asunto(s)

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Anticuerpos Anti-VIH / Vacunas contra el SIDA / Productos del Gen env del Virus de la Inmunodeficiencia Humana / Anticuerpos Neutralizantes Límite: Humans Idioma: En Año: 2016 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Anticuerpos Anti-VIH / Vacunas contra el SIDA / Productos del Gen env del Virus de la Inmunodeficiencia Humana / Anticuerpos Neutralizantes Límite: Humans Idioma: En Año: 2016 Tipo del documento: Article