Application of a plant virus nanoparticle for the creation of antivirals and mucosally-deliverable vaccines and therapeutics.

摘要

Plant viruses such as cowpea mosaic virus (CPMV) that grow to high titers in host plants represent an attractive means of displaying peptides and therapeutic moieties for systemic and mucosal delivery. An inhibitory peptide from the measles virus cellular receptor CD46 presented on CPMV particles was up to 20-fold more effective than the free peptide at blocking measles virus infection of HeLa cells. This CPMV-CD46 chimeric virus also protected between 75--100% of CD46-transgenic mice from measles virus-induced encephalitis and death. CPMV nanoparticles were also studied for their oral bioavailability in the mouse to determine their feasibility as mucosal delivery vehicles. Following oral administration into mice, CPMV trafficked to systemic and mucosal tissues, entering the tissue parenchyma via the bloodstream and remaining in some tissues for up to two to three days. Passive ingestion of CPMV in the form of CPMV-infected leaves led to a similar systemic dissemination to mouse tissues. When a measles virus epitope was displayed on CPMV, preliminary results showed that chimeric virus made with CPMV genomic RNA-1 containing a mutation in the 32K protease cofactor gene presented uncleaved inserts, whereas chimeric virus created with wild-type RNA-1 was cleaved and unstable. The mutation in the protease cofactor gene may thus be important for the display of certain complex peptides on CPMV. Neither batch of chimeric virus induced immune responses upon parenteral and mucosal immunization. Overall, the results of this thesis indicate that the CPMV nanoparticle can be used as novel antivirals and mucosally-deliverable or edible reagents for therapeutic purposes.