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

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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.