Chimeric particles of tobacco mosaic virus as a platform for the development of next-generation nanovaccines

Abstract

The production of vaccines and other proteins in plants for medical purposes offers a number of advantages over other expression systems. The tobacco mosaic virus (TMV) is an appropriate model for the development of a variety of vectors, including those used for the assembly of chimeric particles carrying heterologous peptides on the surface and inducing an effective immune response. To overcome the problems arising during the assembly of such particles from recombinant subunits of the coat protein, peptide linkers, suppressed stop codons, and proteolytic sites are used. To date, it has been shown that TMV-based nanovaccines provide protection against the viruses of influenza A, foot-and-mouth disease, papilloma, and they are also able to overcome B-cell tolerance for cancer-cell suppression. Genetically modified TMV-based virions can accommodate the ions of various metals and act as affinity agents for protein purification.

Optimization of aPlasmodium falciparumcircumsporozoite protein repeat vaccine using the tobacco mosaic virus platform

“…The N and C termini of the TMV capsid point outwards from an assembled TMV disk ( Fig. 1A) and majority of previous vaccine design efforts have used these N and C termini to display epitopes (41,(49)(50)(51)(52). Dedeo et al (53) reported a "circular permutant" of TMV where the N and C termini were re-engineered to the inner pore and a short loop was placed to close the sequence gap.…”

“…We utilized an open source particle technology based on the tobacco mosaic virus (TMV) VLP for this design effort. TMV under physiological conditions assembles into an 18-nm disk that can also further assemble into rod shaped VLPs of up to 300 nm in size (41). The TMV size range and, its repetitive, symmetric, and high-density display of epitopes make them highly attractive for antigen presentation and induction of high titer antibodies (42).…”

Enhanced Stability and Controlled Delivery of MOF-Encapsulated Vaccines and Their Immunogenic Response In Vivo

“…We chose TMV, a 300 nm × 18 nm tubular RNA plant virus, as a model vaccine biomacromolecule owing to extensive data on its in vivo performance as a carrier for engineered and chemically conjugated − epitopes in vaccine development (Scheme ). This chemical modifiability, which can occur on both interior and exterior surfaces independently, has given TMV a unique appeal beyond vaccine development as the structure tolerates attachment of dyes, sensors, , contrast agents, and bioactive molecules. , The multivalent nature of TMV comes from its 2130 identical coat proteins arranged helically around a 4 nm central pore where the viral RNA is located.…”

“…This chemical modifiability, which can occur on both interior and exterior surfaces independently, has given TMV a unique appeal beyond vaccine development as the structure tolerates attachment of dyes, sensors, , contrast agents, and bioactive molecules. , The multivalent nature of TMV comes from its 2130 identical coat proteins arranged helically around a 4 nm central pore where the viral RNA is located. This allows many bioconjugations to the same virus particle, increasing local concentration of active sites and immobilizing them, which is one reason it is thought to be such a useful platform for vaccine development. − …”

Transient expression of virus-like particles in plants: a promising platform for rapid vaccine production

“…The production of chimeric viral particles with efficient virion assembly has been the objective of several studies. To achieve this, certain methods have been based to limit the steric hindrance of the modified coat protein by incorporation of the linker peptides between the viral coat protein and the fused peptide [81]. Furthermore, applying proteolytic site region, suppressed stop codon, -ribosomal skip‖ of translation sequences (such as 2A peptide of the foot-and-mouth disease virus) between the heterologous peptide and the coat protein have been used where the fused product is synthesized along with the wild type coat protein [82].…”