Engineered synthetic virus-like particles and their use in vaccine delivery

Chembiochem. 2011 Jan 3;12(1):100-9. doi: 10.1002/cbic.201000536.

Abstract

Engineered nanoparticles have been designed based on the self-assembling properties of synthetic coiled-coil lipopeptide building blocks. The presence of an isoleucine zipper within the lipopeptide together with the aggregating effects of an N-terminal lipid drives formation of 20-25 nm nanoparticles in solution. Biophysical studies support a model in which the lipid is buried in the centre of the nanoparticle, with 20-30 trimeric helical coiled-coil bundles radiating out into solution. A promiscuous T-helper epitope and a synthetic B-cell epitope mimetic derived from the circumsporozoite protein of Plasmodium falciparum have been linked to each lipopeptide chain, with the result that 60-90 copies of each antigen are displayed over the surface of the nanoparticle. These nanoparticles elicit strong humoral immune responses in mice and rabbits, including antibodies able to cross-react with the parasite, thereby, supporting the potential value of this delivery system in synthetic vaccine design.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Surface / metabolism
  • Circular Dichroism
  • Drug Design*
  • Epitopes, T-Lymphocyte / immunology
  • Immunity, Humoral / immunology
  • Lipopeptides / chemical synthesis
  • Lipopeptides / chemistry*
  • Lipopeptides / immunology*
  • Lipopeptides / metabolism
  • Mice
  • Microscopy, Electron
  • Models, Molecular
  • Molecular Sequence Data
  • Neutron Diffraction
  • Plasmodium falciparum
  • Protein Conformation
  • Rabbits
  • Scattering, Small Angle
  • Vaccines, Synthetic / chemistry
  • Vaccines, Synthetic / immunology
  • Vaccines, Synthetic / metabolism
  • Viruses / chemistry*
  • X-Ray Diffraction

Substances

  • Antigens, Surface
  • Epitopes, T-Lymphocyte
  • Lipopeptides
  • Vaccines, Synthetic