Cooperation of B Cell Lineages in Induction of HIV-1-broadly Neutralizing Antibodies

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / chemistry*
  • AIDS Vaccines / immunology*
  • Amino Acid Sequence
  • Antibodies, Neutralizing / immunology*
  • B-Lymphocytes / immunology
  • HIV Antibodies / immunology*
  • HIV-1 / physiology*
  • Immune Evasion
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Sequence Alignment
  • env Gene Products, Human Immunodeficiency Virus / genetics
  • env Gene Products, Human Immunodeficiency Virus / immunology

Substances

  • AIDS Vaccines
  • Antibodies, Neutralizing
  • HIV Antibodies
  • env Gene Products, Human Immunodeficiency Virus

Associated data

  • GENBANK/KM052327
  • GENBANK/KM052328
  • GENBANK/KM052329
  • GENBANK/KM052330
  • GENBANK/KM052331
  • GENBANK/KM052332
  • GENBANK/KM052333
  • GENBANK/KM052334
  • GENBANK/KM052335
  • GENBANK/KM052336
  • GENBANK/KM052337
  • GENBANK/KM052338
  • GENBANK/KM052339
  • GENBANK/KM052340
  • GENBANK/KM052341
  • GENBANK/KM052342
  • GENBANK/KM052343
  • GENBANK/KM052344