Rapid selection of HIV envelopes that bind to neutralizing antibody B cell lineage members with functional improbable mutations.

Journal Article (Journal Article)

Elicitation of broadly neutralizing antibodies (bnAbs) by an HIV vaccine will involve priming the immune system to activate antibody precursors, followed by boosting immunizations to select for antibodies with functional features required for neutralization breadth. The higher the number of acquired mutations necessary for function, the more convoluted are the antibody developmental pathways. HIV bnAbs acquire a large number of somatic mutations, but not all mutations are functionally important. In this study, we identify a minimal subset of mutations sufficient for the function of the naturally occurring V3-glycan bnAb DH270.6. Using antibody library screening, candidate envelope immunogens that interact with DH270.6-like antibodies containing this set of key mutations are identified and selected in vitro. Our results demonstrate that less complex B cell evolutionary pathways than those naturally observed exist for the induction of HIV bnAbs by vaccination, and they establish rational approaches to identify boosting candidate immunogens.

Full Text

Duke Authors

Cited Authors

  • Swanson, O; Rhodes, B; Wang, A; Xia, S-M; Parks, R; Chen, H; Sanzone, A; Cooper, M; Louder, MK; Lin, BC; Doria-Rose, NA; Bonsignori, M; Saunders, KO; Wiehe, K; Haynes, BF; Azoitei, ML

Published Date

  • August 17, 2021

Published In

Volume / Issue

  • 36 / 7

Start / End Page

  • 109561 -

PubMed ID

  • 34407396

Pubmed Central ID

  • PMC8493474

Electronic International Standard Serial Number (EISSN)

  • 2211-1247

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2021.109561


  • eng

Conference Location

  • United States