Development of Virus-Like Particle Technology from Small Highly Symmetric to Large Complex Virus-Like Particle Structures

Peter Pushko, Paul Pumpens, Elmars Grens
2013 Intervirology  
second generation of VLP carriers is represented by complex particles reconstructed from natural or chimeric structural proteins derived from complex enveloped viruses. Further development of safe and efficient VLP nanotechnology may require a rational combination of both approaches. Recombinant virus-like particles (VLPs) are nanodimensional structures that (1) are built from one or several viral structural constituents in the form of recombinant proteins synthesized in efficient homologous or
more » ... primarily heterologous expression systems (bacteria, yeast, or eukaryotic cell culture); (3) are identical or closely related by their three-dimensional architecture and immunochemical characteristics to naturally occurring viral structures, and (3) lack genomes or infectivity [1][2][3][4][5] . VLPs can be formed from nucleocapsid or envelope proteins alone and the term VLP will be used here to describe any multimolecular structure formed by viral capsid and/ or envelope proteins or by capsid and envelope combinations. The term non-chimeric VLPs is used for particles Abstract Virus-like particle (VLP) technology is a promising approach for the construction of novel vaccines, diagnostic tools, and gene therapy vectors. Initially, VLPs were primarily derived from non-enveloped icosahedral or helical viruses and proved to be viable vaccine candidates due to their effective presentation of epitopes in a native conformation. VLP technology has also been used to prepare chimeric VLPs decorated with genetically fused or chemically coupled epitope stretches selected from immunologically defined target proteins. However, structural constraints associated with the rigid geometrical architecture of icosahedral or helical VLPs pose challenges for the expression and presentation of large epitopes. Complex VLPs derived from non-symmetric enveloped viruses are increasingly being used to incorporate large epitopes and even full-length foreign proteins. Pleomorphic VLPs derived from influenza or other enveloped viruses can accommodate multiple full-length and/or chimeric proteins that can be rationally designed for multifunctional purposes, including multivalent vaccines. Therefore, a
doi:10.1159/000346773 pmid:23594863 fatcat:x5dooq4rsrfxzgpvo3po6xkbse