Engineered Synthetic Virus-Like Particles and Their Use in Vaccine Delivery

Arin Ghasparian, Tina Riedel, Jimy Koomullil, Kerstin Moehle, Christian Gorba, Dmitri I. Svergun, Adam W. Perriman, Stephen Mann, Marco Tamborrini, Gerd Pluschke, John A. Robinson

Research output: Contribution to journalArticle (Academic Journal)

37 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)100-109
Number of pages10
JournalChemBioChem
Volume12
Issue number1
DOIs
Publication statusPublished - 3 Jan 2011

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