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Induction of HIV Neutralizing Antibody Lineages in Mice with Diverse Precursor Repertoires.
Tian, Ming; Cheng, Cheng; Chen, Xuejun; Duan, Hongying; Cheng, Hwei-Ling; Dao, Mai; Sheng, Zizhang; Kimble, Michael; Wang, Lingshu; Lin, Sherry; Schmidt, Stephen D; Du, Zhou; Joyce, M Gordon; Chen, Yiwei; DeKosky, Brandon J; Chen, Yimin; Normandin, Erica; Cantor, Elizabeth; Chen, Rita E; Doria-Rose, Nicole A; Zhang, Yi; Shi, Wei; Kong, Wing-Pui; Choe, Misook; Henry, Amy R; Laboune, Farida; Georgiev, Ivelin S; Huang, Pei-Yi; Jain, Suvi; McGuire, Andrew T; Georgeson, Eric; Menis, Sergey; Douek, Daniel C; Schief, William R; Stamatatos, Leonidas; Kwong, Peter D; Shapiro, Lawrence; Haynes, Barton F; Mascola, John R; Alt, Frederick W.
Afiliación
  • Tian M; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Howard Hughes Medical Institute, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
  • Cheng C; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
  • Chen X; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
  • Duan H; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
  • Cheng HL; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Howard Hughes Medical Institute, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
  • Dao M; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Howard Hughes Medical Institute, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
  • Sheng Z; Department of Biochemistry and Molecular Biophysics and Department of Systems Biology, Columbia University, New York, NY 10032, USA.
  • Kimble M; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Howard Hughes Medical Institute, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
  • Wang L; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
  • Lin S; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Howard Hughes Medical Institute, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
  • Schmidt SD; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
  • Du Z; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Howard Hughes Medical Institute, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
  • Joyce MG; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
  • Chen Y; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Howard Hughes Medical Institute, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
  • DeKosky BJ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
  • Chen Y; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Howard Hughes Medical Institute, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
  • Normandin E; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
  • Cantor E; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Howard Hughes Medical Institute, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
  • Chen RE; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
  • Doria-Rose NA; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
  • Zhang Y; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
  • Shi W; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
  • Kong WP; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
  • Choe M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
  • Henry AR; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
  • Laboune F; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
  • Georgiev IS; Vanderbilt Vaccine Center, Vanderbilt University, Nashville, TN 37232, USA.
  • Huang PY; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Howard Hughes Medical Institute, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
  • Jain S; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Howard Hughes Medical Institute, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
  • McGuire AT; Fred Hutchinson Cancer Research Center, Seattle, WA 02129, USA.
  • Georgeson E; Department of Immunology and Microbial Science and IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Menis S; Department of Immunology and Microbial Science and IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Douek DC; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
  • Schief WR; Department of Immunology and Microbial Science and IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, Cambridge, MA 02129, USA; Harvard University, Cambridge, MA 02129,
  • Stamatatos L; Fred Hutchinson Cancer Research Center, Seattle, WA 02129, USA.
  • Kwong PD; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
  • Shapiro L; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA; Department of Biochemistry and Molecular Biophysics and Department of Systems Biology, Columbia University, New York, NY 10032, USA.
  • Haynes BF; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
  • Mascola JR; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA. Electronic address: jmascola@mail.nih.gov.
  • Alt FW; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Howard Hughes Medical Institute, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. Electronic address: alt@enders.tch.harvard.edu.
Cell ; 166(6): 1471-1484.e18, 2016 Sep 08.
Article en En | MEDLINE | ID: mdl-27610571
ABSTRACT
The design of immunogens that elicit broadly reactive neutralizing antibodies (bnAbs) has been a major obstacle to HIV-1 vaccine development. One approach to assess potential immunogens is to use mice expressing precursors of human bnAbs as vaccination models. The bnAbs of the VRC01-class derive from the IGHV1-2 immunoglobulin heavy chain and neutralize a wide spectrum of HIV-1 strains via targeting the CD4 binding site of the envelope glycoprotein gp120. We now describe a mouse vaccination model that allows a germline human IGHV1-2(∗)02 segment to undergo normal V(D)J recombination and, thereby, leads to the generation of peripheral B cells that express a highly diverse repertoire of VRC01-related receptors. When sequentially immunized with modified gp120 glycoproteins designed to engage VRC01 germline and intermediate antibodies, IGHV1-2(∗)02-rearranging mice, which also express a VRC01-antibody precursor light chain, can support the affinity maturation of VRC01 precursor antibodies into HIV-neutralizing antibody lineages.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: VIH-1 / Inmunización / Cadenas Pesadas de Inmunoglobulina / Células Precursoras de Linfocitos B / Anticuerpos Neutralizantes / Anticuerpos Monoclonales Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Cell Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: VIH-1 / Inmunización / Cadenas Pesadas de Inmunoglobulina / Células Precursoras de Linfocitos B / Anticuerpos Neutralizantes / Anticuerpos Monoclonales Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Cell Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos