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Cell. 2014 Jul 31;158(3):481-91. doi: 10.1016/j.cell.2014.06.022. Epub 2014 Jul 24.

Cooperation of B cell lineages in induction of HIV-1-broadly neutralizing antibodies.

Author information

  • 1Duke University Human Vaccine Institute, Departments of Medicine, Surgery, Pediatrics and Immunology, Duke University School of Medicine, Durham NC 27710, USA; The Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery at Duke University, Durham NC 27710, USA. Electronic address: fgao@duke.edu.
  • 2Duke University Human Vaccine Institute, Departments of Medicine, Surgery, Pediatrics and Immunology, Duke University School of Medicine, Durham NC 27710, USA; The Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery at Duke University, Durham NC 27710, USA.
  • 3Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • 4Departments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • 5UNC Project, Lilongwe, Malawi; Departments of Health Policy and Management, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • 6Departments of Medicine, Epidemiology and Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • 7Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87544, USA.
  • 8Department of Microbiology, Boston University, Boston, MA 02215, USA.
  • 9Duke University Human Vaccine Institute, Departments of Medicine, Surgery, Pediatrics and Immunology, Duke University School of Medicine, Durham NC 27710, USA; The Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery at Duke University, Durham NC 27710, USA. Electronic address: barton.haynes@duke.edu.

Abstract

Development of strategies for induction of HIV-1 broadly neutralizing antibodies (bnAbs) by vaccines is a priority. Determining the steps of bnAb induction in HIV-1-infected individuals who make bnAbs is a key strategy for immunogen design. Here, we study the B cell response in a bnAb-producing individual and report cooperation between two B cell lineages to drive bnAb development. We isolated a virus-neutralizing antibody lineage that targeted an envelope region (loop D) and selected virus escape mutants that resulted in both enhanced bnAb lineage envelope binding and escape mutant neutralization-traits associated with increased B cell antigen drive. Thus, in this individual, two B cell lineages cooperated to induce the development of bnAbs. Design of vaccine immunogens that simultaneously drive both helper and broadly neutralizing B cell lineages may be important for vaccine-induced recapitulation of events that transpire during the maturation of neutralizing antibodies in HIV-1-infected individuals.

Copyright © 2014 Elsevier Inc. All rights reserved.

PMID:
25065977
[PubMed - indexed for MEDLINE]
PMCID:
PMC4150607
Free PMC Article
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