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，导致300万至500万严重病例和25万至50万死亡。基于使用根癌农杆菌在植物中瞬时表达抗原的疫苗生产平台允许有效生产可快速放大的亚单位疫苗。然而，植物对农杆菌的反应具有抗微生物防御反应，这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，最终目标是减弱植物防御反应，提高蛋白质表达。该项目将采取双管齐下的方法：修改细菌，使其抑制防御反应，并确定植物基因，其抑制将导致减弱的防御反应。这将有助于提高蛋白质产量和质量。改变的细菌可以直接掺入到当前的疫苗生产方法中，并且候选植物基因将在突变的本氏烟草植物中变得无功能。一旦产生，突变植物系也可以并入疫苗生产平台。这项研究将直接有利于加拿大疫苗制造业。此外，这一平台还将提高全球疫苗供应链的灵活性和稳定性，这将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.