Rapid and Scalable Production of SARS-CoV-2 Spike Protein in Plants for Serological Testing of COVID-19

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Rapid detection of SARS-CoV-2-infected individuals in the population is essential for combating the current COVID 19 pandemic. Serological assays are widely accepted as the best approach for SARS-CoV-2 diagnostic tests; they can identify non-symptomatic and previously infected individuals, be used for contact tracing, and are important in ongoing vaccine development. Serological testing kits are currently under development by Canadian companies, including our primary partner bioLytical Laboratories. The large-scale production of such testing kits requires a cost-effective and scalable source of the SARS-CoV-2 spike protein, which is currently in very short supply. Our proposal aims to develop a rapid and scalable method for producing this protein in plants, and in collaboration with our partner organizations, to demonstrate its suitability in serological testing assays. We will use the Nicotiana benthamiana agro-infiltration method for rapid expression, as it allows for the production of recombinant protein in greenhouse-grown plants within one week of transformation (transfection). The approach has been successfully used for producing many other viral proteins, including the spike protein from the SARS coronavirus. We will first demonstrate the overall feasibility of this approach, and then express several variants of the SARS-CoV-2 spike protein. Expressed spike will be purified using standard affinity methods and assayed for purity. Our partner organization, bioLytical Laboratories, will then test the plant-produced spike protein in their SARS-CoV-2 serological assays system, and compare its binding properties with those of mammalian cell-produced spike protein. In parallel, our second partner organziation, ImmunoPrecise Antibodies (Canada), will determine how the plant-produced spike protein reacts with available SARS-CoV-2 antibodies. These experiments will determine if N. benthamiana-produced spike protein can be used as a basis for serological test kits. The availability of such an easily scaled and economical source of SARS-CoV-2 spike protein would have a direct impact on Canada's capacity to produce serological testing kits, and would be a critical element in Canada's response to the current COVID-19 pandemic.