Using quantitative proteomics to optimize Euglena gracilis as a sole-source COVID-19 vaccine delivery platform

SARS-CoV-2是一种新型冠状病毒，于2019年底出现，此后在全球迅速传播，引发了前所未有的全球危机。由新冠肺炎引起的SARS-CoV-2对全球健康和经济的影响越来越大，这突显了除了可获得的疫苗外，还需要敏感和具体的工具来监测正在传播的病毒，以保护人类免受病毒的侵害。独一无二的是，细小眼虫(Euglena Gracilis)代表了一种多功能有机体，具有成为开发独家来源新冠肺炎疫苗的改变游戏规则的生物技术平台的潜力。Euglena能够在不同的生理条件下采取多种生长策略，提供出色的生物适应性和一系列可培养条件。此外，它还生产天然佐剂副尼龙，目前正在探索将其作为疫苗的非化学佐剂。利用定量蛋白质组学方法，我们建议分析Euglena胞外和分泌蛋白质组中的蛋白质组和糖蛋白质组的变化，以确定关键的蛋白质网络和蛋白质特征(例如转运肽/靶向多肽)，这些蛋白质网络和蛋白质特征可用于最大化疫苗生产的抗原呈递或可持续血清学测试发展的分泌。此外，利用缺乏副尼龙的Euglena，我们还致力于鉴定有助于优化副尼龙生产的蛋白质。最后，我们将定量评估表达新冠肺炎刺突蛋白的眼镜蛇系蛋白质组的变化。这将有助于将Euglena发展成为新冠肺炎疫苗的独家生产平台。传染病专家一再强调，新冠肺炎等人畜共患病毒性疾病的暴发预计在下个世纪将在频率和数量上增加。因此，我们建议将纤细眼虫发展为能够在新疫苗生产中快速部署的单一生物体平台，这也代表了为未来的暴发和大流行做准备的一种新的必要性。

SARS-CoV-2 is a novel coronavirus that emerged in late 2019 and has since rapidly spread across the world causing an unprecedented global crisis. The growing impact of SARS-CoV-2 caused COVID-19 on global health and the economy has highlighted the need for sensitive and specific tools to surveil the circulating virus in addition to accessible vaccines to protect human populations against the virus. Uniquely, Euglena gracilis (Euglena) represents a versatile organism that holds the potential of being a game-changing biotechnology platform for the development of a sole-source COVID-19 vaccine. Euglena is capable of multiple growth strategies under diverse physiological conditions, providing exceptional biological adaptiveness and range of culturable conditions. Moreover, it produces the natural adjuvant paramylon that is being explored as a non-chemical adjuvant agent for vaccines. Using quantitative proteomic approaches, we propose to analyze proteome and glycoproteome changes in the Euglena extracellular and secreted proteome in order to identify key protein networks and protein features (e.g. transit / targeting peptides) that can be exploited in maximizing either antigen presentation for vaccine production or secretion for sustainable serological test development. Furthermore, using paramylon deficient Euglena we also aim to identify proteins that will contribute to the optimization of paramylon production. Lastly, we will quantitatively assess changes in the proteome of Euglena lines expressing COVID-19 spike proteins. This will contribute to refining the development of Euglena as a sole-source production platform for a COVID-19 vaccine. Infectious disease experts have repeatedly stressed that outbreaks of zoonotic viral diseases such as COVID-19 are expected to increase in frequency and number over the next century. Our proposed development of Euglena gracilis as a single organism platform capable of rapid deployment in the production of new vaccines therefore also represents an emerging necessity in preparing for future outbreaks and pandemics.