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Sci Immunol. 2017 Jan 27;2(7). pii: eaal2200. doi: 10.1126/sciimmunol.aal2200.

Potent and broad HIV-neutralizing antibodies in memory B cells and plasma.

Author information

1
Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
2
Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850, USA.
3
Department of Chemical Engineering, University of Texas at Austin, Austin, TX 78712, USA.
4
Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
5
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20814, USA.
6
Vanderbilt Vaccine Center and Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
7
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
8
Centre for HIV and STIs, National Institute for Communicable Diseases, Johannesburg 2131, South Africa.
9
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.
10
Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
11
Departments of Microbiology and Mathematics & Statistics, Boston University School of Medicine, Boston, MA 02118, USA.
12
Department of Pathology, Duke University School of Medicine, Durham, NC 27710, USA.
13
University of North Carolina Project-Malawi, Kamuzu Central Hospital, Lilongwe, Malawi.
14
Departments of Medicine, Epidemiology, and Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599, USA.
15
Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA.
16
Department of Immunology, Duke University School of Medicine, Durham, NC 27710, USA.
17
Department of Pediatrics, Duke University School of Medicine, Durham, NC 27710, USA.
18
Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, USA.
19
Department of Chemical Engineering, University of Texas at Austin, Austin, TX 78712, USA. barton.haynes@dm.duke.edu gg@che.utexas.edu.
20
Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA.
21
Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA. barton.haynes@dm.duke.edu gg@che.utexas.edu.

Abstract

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.

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