Improving a plant vaccine platform modulation of the plant defence system

每年约有5-15%的世界人口感染流感，造成300万至500万严重病例和25万至50万人死亡。利用农杆菌在植物中短暂表达抗原的疫苗生产平台允许高效生产亚单位疫苗，可迅速扩大规模。然而，植物对农杆菌的抗微生物防御反应会降低蛋白质的产量和质量。将进行研究，以表征植物对农杆菌的免疫反应，最终目标是减轻植物的防御反应和改善蛋白质表达。该项目将采取双管齐下的方法：对细菌进行修饰，使其抑制防御反应，并鉴定植物基因，这些基因的抑制将导致防御反应减弱。总之，这将有助于提高蛋白质产量和质量。改变的细菌可以直接纳入目前的疫苗生产方法，候选植物基因将在突变的本菌烟草植物中失去功能。一旦产生，突变株也可以纳入疫苗生产平台。这项研究将直接使加拿大疫苗制造业受益。此外，这一平台将提高全球疫苗供应链的灵活性和稳定性，为加拿大人的健康带来重大利益。

Approximately 5-15% of the world population is infected annually with influenza, resulting in three to five million severe cases and 250 000 to 500 000 deaths. Vaccine production platforms based on transient expression of antigens in plants using Agrobacterium tumefaciens allow for efficient production of subunit vaccines that can be rapidly scaled up. However, plants react to Agrobacterium with an antimicrobial defense response which can decrease protein production and quality. Research will be undertaken to characterize the immune response of the plant against Agrobacterium, with the ultimate goal of attenuating plant defense responses an improving protein expression. This project will undertake a two-pronged approach: modification of the bacterium so that it suppresses the defense response and identification of plant genes whose suppression will result in an attenuated defense response. Together, this will allow for an increase in protein production and quality. Altered bacteria can be directly incorporated into current vaccine production methods and candidate plant genes will be rendered non-functional in mutant Nicotiana benthamiana plants. Once generated, mutant plant lines can also be incorporated into vaccine production platforms. This research will directly benefit the Canadian vaccine manufacturing industry. In addition, this platform will lead to greater flexibility and stability in the global vaccine supply chain, which will provide significant benefits to the health of Canadians.