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

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.

Nanoparticle-Based Nicotine Vaccine

“…VLPs are composed of viral proteins expressed in vitro upon which the selfassembly forms regularly structured particles in the 20-100 nm size range (Ghasparian et al 2011 ). Several VLP-based products have successfully entered medical practice (Plotkin et al 2012 ), and a several dozen of VLP-based vaccine candidates are either in clinical trials or undergoing preclinical evaluation (Clinicaltrials.gov 2015 ).…”

A silk purse from a sow's ear—bioinspired materials based on α-helical coiled coils

“…The self-assembly polypeptide nanoparticle (SAPN) strategy has other guises (e.g. synthetic virus-like particle; SVLP) and derivations such as lipoprotein virus-like particles [49] and coiled coil based vesicles with membrane fusion properties [50 ]. Using such technologies, vaccines to malaria [51,52], toxoplasma [53] and HIV [54] are being developed, but the technology is also a useful scientific tool to target specific epitopes in any protein of interest for example [55].…”

Applications of immunochemistry in human health: advances in vaccinology and antibody design (IUPAC Technical Report)

“…Alternatively, a chemical coupling approach can be taken to conjugate epitopes to VLPs. One chemical approach reported recently exploits the unique chemical and physical properties of designed synthetic lipopeptide building blocks that spontaneously self-assemble in aqueous buffers into homogeneous nanoparticles in the 20-30-nm size range, called synthetic VLPs (SVLPs) [191]. Synthetic lipopeptides containing a "virally derived" coiled-coil (CC) sequence coupled through a linker at its N-terminus to a phospholipid are also able to spontaneously self-assemble in aqueous buffers into homogeneous nanoparticles [192].…”

“…Processing then occurs more slowly by proteolytic cleavage of the lipopeptides. The processing is highly effective as evidenced by the strong immune responses induced by SVLPs in small animals, without the need for external adjuvants [191,192,194].…”