Plant virus expression vectors offer an alternative plant based expression system for the production of novel products. Unlike plant transformation, which takes many months to produce products, plant virus expression vectors routinely produce product within 1 to 3 weeks after infection of the host plant. In addition, much higher yields of product are obtained (estimates are as high as 250Kg of vaccine produced per hectare per month) thus lowering production costs. Recently, products based on this technology have entered clinical trails in the United States and Europe, joining other novel plant-produced therapeutic products such as "plantibodies" . In addition to their use as a production system, plant virus expression vectors have recently been used as vaccine delivery systems, much as has vaccinia virus, but with the advantage that plant viruses are unable to replicate in humans (or in any mamallian system) making them potentially much safer for use in human immunisation programs. Malaysia has the ideal plant growing conditions and expertise to harness this technology for the development of therapeutic products tailored for locally important variants of diseases for use in disease prevention and treatment. Furthermore, development time to express new proteins in the system is only a matter of weeks. The system is also easily adaptable to scale up or down (by using more or less plants) to required production levels making it feasible to produce "designer" treatments suited to an individuals' genetic requirements, or for mass production of a widely used product. By developing a local capacity for this technology, Malaysia will be able to rapidly develop our own vaccines for new and emerging diseases and, in the longer term, for individually tailored treatments.

This project will aim to develop local expression vectors based on plant viruses which can be used both for the production of therapeutic and diagnostic proteins (short term) and developed as a novel vaccine and drug delivery system for locally important diseases, for human immunization programs and for individually tailored treatment programs (long term).

 

EXECUTIVE SUMMARY

Project Title:
Development and Application of Novel Plant Virus Vector Systems for Production
of Biopharmaceuticals and for Vaccine Delivery

 

 

Period of the project : 3 Years (2001 - 2004)

Achievements

Progress/Achievements for year one

New Process :

1- Functional studies of the resultant recombinant chimeric vector involved studies on in-vitro transcription and processing.
2- This was followed by testing of the infectivity of the transcript in plants to enable study of the level of expression stability and viability of the recombinant vectors in host plants.

Discovery :

1- The chimeric construct has also been successfully developed and in-vitro transcription demonstrated by Northern Blots. The transcripts were shown to be infectious and capable of inducing systemic infection in tobacco plants.
2- As CGMV movement in plants requires intact capsid, it is infered that intact chimeric particles were formed. This is confirmed by western blot and electron microscopy. The particles produced will be used for immunological and pharmacological analysis.

Publications;

1.Ooi,A.S.,M.Nishiguchi,M.Ukgaki,S.H.Tan,W.S.Tan,
A.R.Noorsaadah and R.Y.Othman (2002) Recombinant fusion of HbsAg a-determinant with the coat protein of Cucumber Green Mottle Tobamovirus (CGGMV), Proceedings,2nd Symposium of the Malaysian Society of Microbiology,pp56-59
2- Ooi,A.S.,M.Nishiguchi,M.Ukgaki,S.H.Tan,W.S.Tan,
A.R.Noorsaadah and R.Y.Othman (2002),Application of a novel Plant virus vector as a Vaccine delivery system,Abstracts of the 13th MSMMBB Scientific meeting.