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

被引：46

作者：

Ghasparian, Arin ^{[1
]}

Riedel, Tina ^{[1
]}

Koomullil, Jimy ^{[1
]}

Moehle, Kerstin ^{[1
]}

Gorba, Christian ^{[2
]}

Svergun, Dmitri I. ^{[2
]}

Perriman, Adam W. ^{[3
]}

Mann, Stephen ^{[3
]}

Tamborrini, Marco ^{[4
,5
]}

Pluschke, Gerd ^{[4
,5
]}

Robinson, John A. ^{[1
]}

机构：

[1] Univ Zurich, Dept Chem, CH-8057 Zurich, Switzerland

[2] EMBL Hamburg, D-22603 Hamburg, Germany

[3] Univ Bristol, Sch Chem, Ctr Organized Matter Chem, Bristol BS8 1TS, Avon, England

[4] Swiss Trop & Publ Hlth Inst, CH-4051 Basel, Switzerland

[5] Univ Basel, CH-4003 Basel, Switzerland

来源：

CHEMBIOCHEM | 2011年 / 12卷 / 01期

基金：

英国工程与自然科学研究理事会; 瑞士国家科学基金会;

关键词：

biophysics; immunology; nanoparticles; self-assembly; viruses; SMALL-ANGLE SCATTERING; HELICAL COILED-COIL; B-CELL ACTIVATION; DENDRITIC CELLS; MOLECULAR ARCHITECTURE; SECONDARY STRUCTURE; CRYSTAL-STRUCTURE; BUILDING-BLOCKS; PROTEIN; MALARIA;

D O I：

10.1002/cbic.201000536

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：100 / 109

页数：10

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