Engineered synthetic virus-like particles and their use in vaccine delivery.
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.
Department of Chemistry, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
Arin
A
Ghasparian
Tina
T
Riedel
Jimy
J
Koomullil
Kerstin
K
Moehle
Christian
C
Gorba
Dmitri I
DI
Svergun
Adam W
AW
Perriman
Stephen
S
Mann
Marco
M
Tamborrini
Gerd
G
Pluschke
John A
JA
Robinson
D000595:Amino Acid Sequence; D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D002942:Circular Dichroism; D015195:Drug Design; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D056724:Immunity, Humoral / Q000276:immunology; D055666:Lipopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008854:Microscopy, Electron; D008958:Models, Molecular; D008969:Molecular Sequence Data; D033363:Neutron Diffraction; D010963:Plasmodium falciparum; D011487:Protein Conformation; D011817:Rabbits; D053838:Scattering, Small Angle; D014614:Vaccines, Synthetic / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D014780:Viruses / Q000737:chemistry*; D014961:X-Ray Diffraction
D000954:Antigens, Surface; D018984:Epitopes, T-Lymphocyte; D055666:Lipopeptides; D014614:Vaccines, Synthetic