A novel strategy to mimic discontinuous protective epitopes using a synthetic scaffold

Vaccine. 2007 Sep 17;25(37-38):6807-17. doi: 10.1016/j.vaccine.2007.06.027. Epub 2007 Jul 26.

Abstract

Although vaccines have been used for a long time and different types of vaccines have been developed, as yet no fully synthetic vaccines have been produced. The production of fully synthetic vaccines has probably not been realized so far due to the structural limitations of linear synthetic peptides to mimic the native shape of protein fragments which is often needed to induce protective antibodies. In this report we used the Bordetella pertussis protein pertactin as a model and show that a novel synthetic scaffold can be used to mimic structurally defined epitopes by confined presentation of several different peptide arms. Guided by modelling a construct was synthesized that induced protective antibodies directed towards a discontinuous epitope. This approach opens up the possibility to the design of new and fully synthetic vaccines that can induce protective antibodies.

MeSH terms

  • Animals
  • Antibodies / immunology
  • Bacterial Outer Membrane Proteins / chemical synthesis
  • Bacterial Outer Membrane Proteins / chemistry*
  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Outer Membrane Proteins / immunology*
  • Bordetella pertussis / immunology
  • Crystallography, X-Ray
  • Epitopes / chemistry*
  • Epitopes / immunology*
  • Mice
  • Models, Molecular
  • Molecular Mimicry / immunology*
  • Molecular Structure
  • Mutation / genetics
  • Virulence Factors, Bordetella / chemical synthesis
  • Virulence Factors, Bordetella / chemistry*
  • Virulence Factors, Bordetella / genetics
  • Virulence Factors, Bordetella / immunology*

Substances

  • Antibodies
  • Bacterial Outer Membrane Proteins
  • Epitopes
  • Virulence Factors, Bordetella
  • pertactin