Potent and broad HIV-neutralizing antibodies in memory B cells and plasma.
Autor: | Williams LD; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA., Ofek G; Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850, USA., Schätzle S; Department of Chemical Engineering, University of Texas at Austin, Austin, TX 78712, USA., McDaniel JR; Department of Chemical Engineering, University of Texas at Austin, Austin, TX 78712, USA., Lu X; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA., Nicely NI; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA., Wu L; Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850, USA., Lougheed CS; Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850, USA., Bradley T; 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., Louder MK; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20814, USA., McKee K; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20814, USA., Bailer RT; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20814, USA., O'Dell S; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20814, USA., Georgiev IS; Vanderbilt Vaccine Center and Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA., Seaman MS; Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA., Parks RJ; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA., Marshall DJ; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA., Anasti K; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA., Yang G; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA., Nie X; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA., Tumba NL; Centre for HIV and STIs, National Institute for Communicable Diseases, Johannesburg 2131, South Africa.; Centre for the AIDS Programme of Research in South Africa (CAPRISA), Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Congella 4013, South Africa., 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., Wagh K; Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545, USA., Korber B; Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545, USA., Kepler TB; Departments of Microbiology and Mathematics & Statistics, Boston University School of Medicine, Boston, MA 02118, USA., Munir Alam S; 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.; Department of Pathology, Duke University School of Medicine, Durham, NC 27710, USA., Morris L; Centre for HIV and STIs, National Institute for Communicable Diseases, Johannesburg 2131, South Africa.; Centre for the AIDS Programme of Research in South Africa (CAPRISA), Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Congella 4013, South Africa., Kamanga G; University of North Carolina Project-Malawi, Kamuzu Central Hospital, Lilongwe, Malawi., Cohen MS; Departments of Medicine, Epidemiology, and Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599, USA., 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., Xia SM; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, 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., 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., 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., Mascola JR; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20814, USA., Moody MA; 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.; Department of Pediatrics, Duke University School of Medicine, Durham, NC 27710, USA., Saunders KO; 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., 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., Tomaras GD; 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 Immunology, Duke University School of Medicine, Durham, NC 27710, USA.; Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, USA., Georgiou G; Department of Chemical Engineering, University of Texas at Austin, Austin, TX 78712, USA. barton.haynes@dm.duke.edu gg@che.utexas.edu.; Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA., Haynes BF; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA. barton.haynes@dm.duke.edu gg@che.utexas.edu.; Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.; Department of Immunology, Duke University School of Medicine, Durham, NC 27710, USA. |
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Jazyk: | angličtina |
Zdroj: | Science immunology [Sci Immunol] 2017 Jan 27; Vol. 2 (7). |
DOI: | 10.1126/sciimmunol.aal2200 |
Abstrakt: | Induction of broadly neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development. Antibody 10E8, reactive with the distal portion of the membrane-proximal external region (MPER) of HIV-1 gp41, is broadly neutralizing. However, the ontogeny of distal MPER antibodies and the relationship of memory B cell to plasma bnAbs are poorly understood. HIV-1-specific memory B cell flow sorting and proteomic identification of anti-MPER plasma antibodies from an HIV-1-infected individual were used to isolate broadly neutralizing distal MPER bnAbs of the same B cell clonal lineage. Structural analysis demonstrated that antibodies from memory B cells and plasma recognized the envelope gp41 bnAb epitope in a distinct orientation compared with other distal MPER bnAbs. The unmutated common ancestor of this distal MPER bnAb was autoreactive, suggesting lineage immune tolerance control. Construction of chimeric antibodies of memory B cell and plasma antibodies yielded a bnAb that potently neutralized most HIV-1 strains. (Copyright © 2017, American Association for the Advancement of Science.) |
Databáze: | MEDLINE |
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