Multi-Donor Longitudinal Antibody Repertoire Sequencing Reveals the Existence of Public Antibody Clonotypes in HIV-1 Infection

Cell Host Microbe. 2018 Jun 13;23(6):845-854.e6. doi: 10.1016/j.chom.2018.05.001. Epub 2018 May 31.

Abstract

Characterization of single antibody lineages within infected individuals has provided insights into the development of Env-specific antibodies. However, a systems-level understanding of the humoral response against HIV-1 is limited. Here, we interrogated the antibody repertoires of multiple HIV-infected donors from an infection-naive state through acute and chronic infection using next-generation sequencing. This analysis revealed the existence of "public" antibody clonotypes that were shared among multiple HIV-infected individuals. The HIV-1 reactivity for representative antibodies from an identified public clonotype shared by three donors was confirmed. Furthermore, a meta-analysis of publicly available antibody repertoire sequencing datasets revealed antibodies with high sequence identity to known HIV-reactive antibodies, even in repertoires that were reported to be HIV naive. The discovery of public antibody clonotypes in HIV-infected individuals represents an avenue of significant potential for better understanding antibody responses to HIV-1 infection, as well as for clonotype-specific vaccine development.

Keywords: B cells; HIV-1; antibodies; antibody repertoire; computational biology; immunology; next-generation sequencing; public antibodies; systems immunology.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antibodies, Neutralizing / blood
  • Antibodies, Neutralizing / chemistry
  • Antibodies, Neutralizing / genetics*
  • Antibodies, Neutralizing / immunology
  • Antibody Formation / immunology*
  • HIV Antibodies / blood
  • HIV Antibodies / chemistry
  • HIV Antibodies / genetics*
  • HIV Antibodies / immunology
  • HIV Infections / blood
  • HIV Infections / immunology*
  • HIV-1 / immunology*
  • Humans
  • Immunity, Humoral / immunology
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / virology
  • Longitudinal Studies
  • RNA / blood
  • RNA / immunology
  • Sequence Analysis, Protein
  • Sequence Analysis, RNA
  • Single-Cell Analysis

Substances

  • Antibodies, Neutralizing
  • HIV Antibodies
  • RNA