Designing string-of-beads vaccines with optimal spacers

Genome Med. 2016 Jan 26;8(1):9. doi: 10.1186/s13073-016-0263-6.

Abstract

String-of-beads polypeptides allow convenient delivery of epitope-based vaccines. The success of a polypeptide relies on efficient processing: constituent epitopes need to be recovered while avoiding neo-epitopes from epitope junctions. Spacers between epitopes are employed to ensure this, but spacer selection is non-trivial.We present a framework to determine optimally the length and sequence of a spacer through multi-objective optimization for human leukocyte antigen class I restricted polypeptides. The method yields string-of-bead vaccines with flexible spacer lengths that increase the predicted epitope recovery rate fivefold while reducing the immunogenicity from neo-epitopes by 44% compared to designs without spacers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • DNA, Intergenic
  • Epitopes / genetics
  • Epitopes / immunology*
  • Genes, MHC Class I
  • Humans
  • Models, Genetic
  • Models, Immunological
  • Vaccines, DNA / genetics*
  • Vaccines, DNA / immunology

Substances

  • DNA, Intergenic
  • Epitopes
  • Vaccines, DNA