B-cell-lineage immunogen design in vaccine development with HIV-1 as a case study.

Journal Article (Journal Article)

Failure of immunization with the HIV-1 envelope to induce broadly neutralizing antibodies against conserved epitopes is a major barrier to producing a preventive HIV-1 vaccine. Broadly neutralizing monoclonal antibodies (BnAbs) from those subjects who do produce them after years of chronic HIV-1 infection have one or more unusual characteristics, including polyreactivity for host antigens, extensive somatic hypermutation and long, variable heavy-chain third complementarity-determining regions, factors that may limit their expression by host immunoregulatory mechanisms. The isolation of BnAbs from HIV-1-infected subjects and the use of computationally derived clonal lineages as templates provide a new path for HIV-1 vaccine immunogen design. This approach, which should be applicable to many infectious agents, holds promise for the construction of vaccines that can drive B cells along rare but desirable maturation pathways.

Full Text

Duke Authors

Cited Authors

  • Haynes, BF; Kelsoe, G; Harrison, SC; Kepler, TB

Published Date

  • May 7, 2012

Published In

Volume / Issue

  • 30 / 5

Start / End Page

  • 423 - 433

PubMed ID

  • 22565972

Pubmed Central ID

  • PMC3512202

Electronic International Standard Serial Number (EISSN)

  • 1546-1696

Digital Object Identifier (DOI)

  • 10.1038/nbt.2197


  • eng

Conference Location

  • United States