B-cell-lineage Immunogen Design in Vaccine Development With HIV-1 as a Case Study

Nat Biotechnol. 2012 May 7;30(5):423-33. doi: 10.1038/nbt.2197.

Abstract

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.

Publication types

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

MeSH terms

  • AIDS Vaccines / chemistry
  • Antibodies / chemistry
  • Antibodies, Monoclonal / chemistry
  • B-Lymphocytes / cytology*
  • Binding Sites
  • Biotechnology / methods
  • Cell Lineage
  • Cell Proliferation
  • Dimerization
  • Drug Design
  • Epitopes / chemistry
  • HIV Antibodies / immunology
  • HIV-1 / metabolism*
  • Humans
  • Immunogenetics
  • Mutation
  • Neutralization Tests
  • Vaccines / metabolism

Substances

  • AIDS Vaccines
  • Antibodies
  • Antibodies, Monoclonal
  • Epitopes
  • HIV Antibodies
  • Vaccines