Poly- and autoreactivity of HIV-1 bNAbs: implications for vaccine design.

Published online

Journal Article (Review)

A central puzzle in HIV-1 research is the inability of vaccination or even infection to reliably elicit humoral responses against broadly neutralizing epitopes in the HIV-1 envelope protein. In infected individuals, broadly neutralizing antibodies (bNAbs) do arise in a substantial minority, but only after 2 or more years of chronic infection. All known bNAbs possess at least one of three traits: a high frequency of somatic hypermutation, a long third complementarity determining region in the antibody heavy chain (HCDR3), or significant poly- or autoreactivity. Collectively, these observations suggest a plausible explanation for the rarity of many types of bNAbs: namely, that their generation is blocked by immunological tolerance or immune response checkpoints, thereby mandating that B cells take a tortuous path of somatic evolution over several years to achieve broadly neutralizing activity. In this brief review, we discuss the evidence for this tolerance hypothesis, its implications for HIV-1 vaccine design, and potential ways to access normally forbidden compartments of the antibody repertoire by modulating or circumventing tolerance controls.

Full Text

Duke Authors

Cited Authors

  • Finney, J; Kelsoe, G

Published Date

  • July 28, 2018

Published In

Volume / Issue

  • 15 / 1

Start / End Page

  • 53 -

PubMed ID

  • 30055635

Pubmed Central ID

  • 30055635

Electronic International Standard Serial Number (EISSN)

  • 1742-4690

Digital Object Identifier (DOI)

  • 10.1186/s12977-018-0435-0

Language

  • eng

Conference Location

  • England