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


Ghasparian, A; Riedel, T; Koomullil, J; Moehle, K; Gorba, C; Svergun, D I; Perriman, A W; Mann, S; Tamborrini, M; Pluschke, G; Robinson, J A (2011). Engineered synthetic virus-like particles and their use in vaccine delivery. ChemBioChem, 12(1):100-109.

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.

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Language:English
Date:3 January 2011
Deposited On:24 Jan 2011 14:18
Last Modified:05 Apr 2016 14:31
Publisher:Wiley VCH
ISSN:1439-4227
Funders:SNF
Publisher DOI:https://doi.org/10.1002/cbic.201000536
PubMed ID:21132689

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