Cucumber green mottle mosaic virus as a Nanoparticle: Biodistribution, immunostimulation and expression / Lee Wei Wei

Lee , Wei Wei (2022) Cucumber green mottle mosaic virus as a Nanoparticle: Biodistribution, immunostimulation and expression / Lee Wei Wei. PhD thesis, Universiti Malaya.

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Abstract

Viral nanoparticles (VNPs) derived from plant viruses have many advantages due to their bio-compatibility and bio-degradability in vivo, ability to self-assemble in 3 dimensions and capacity for large scale production. Compared to the animal VNPs, plant VNPs are likely to be less or non-pathogenic to human. Cucumber Green Mottle Mosaic Virus (CGMMV) is a single stranded, positive sense RNA virus from the family of Tobamovirus that has the potential to be developed as a nanoparticle for vaccine and adjuvant applications. In this study, CGMMV nanoparticles were found to be produced more efficiently in its native host Cucumis melo var Earl favorite compared to the other alternative local varieties. In vivo study of subcutaneously injected CGMMV nanoparticles in a mouse model demonstrated that it is distributed in a wide range of tissues without causing any toxicity and inflammation. It is also able to induce high level of antibody production without the need of adjuvants. Infectivity of CGMMV nanoparticles extracted from the mouse tissues however is greatly reduced. Moreover, CGMMV nanoparticles can act as immunostimulator in vitro by stimulating the innate immune response and confer protection against Vesicular stomatitis virus (VSV) and Sendai virus (SeV) infection in RAW246.7 cells. Lastly, chimeric CGMMV vectors were engineered to express selected M1 influenza epitopes at the 3’ terminal of coat protein. The epitopes can be co-expressed at the surface of the viral coat protein during replication in plants. However, no significant difference in immune response was observed between the chimeric and wild-type CGMMV nanoparticles upon testing in mice. Taken together, the results suggest that CGMMV nanoparticle is a potential vaccine carrier and adjuvant candidate. Further study is needed to tease out the underlying factor required for CGMMV chimeric nanoparticles to induce immune response against influenza epitopes.

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