Corona diagnostics in plants

As the crisis progresses, testing methods that provide information about patients’ immune status will play a crucial role in the relaxation of control measures, since such assays—used to measure virus-specific antibody responses—enable “clearance testing.” In this way, individuals can be identified who, at least in the medium term, are not at risk of illness and cannot transmit the virus further.

The production of such immunoassays requires large quantities of viral surface proteins, which must be produced using recombinant expression systems. As in many areas related to pandemic response, there are also significant bottlenecks in the production of these assay reagents, since microbial systems cannot be used to produce such complex molecules.

The plant-based production platform established at the IME represents a suitable system to fill this gap.

As part of the CDP project, the expertise and infrastructure available at Fraunhofer IME will be utilized to produce variants of the SARS-CoV-2 spike protein transiently in plants in order to bridge current shortages of coronavirus antigens needed for immunological rapid tests.

The recombinant SARS-CoV-2 surface antigens produced in plants are intended to serve as a fully equivalent alternative to proteins conventionally manufactured in animal or human cell cultures and to be used as assay reagents in COVID-19 rapid tests.

The combination of IME’s transient plant production platform and an automated vertical farm for continuous plant cultivation is ideally suited to temporarily expand production capacity for the manufacture of recombinant proteins used in immunoassays designed to detect SARS-CoV-2–specific antibody responses.

Within the CDP project, up to eight different construct variants based on the SARS-CoV-2 spike protein will be examined with regard to product yield, quality, production cost, and functionality. After design and cloning, the constructs will be transferred into Agrobacterium and used for transient expression at laboratory scale. The expressed proteins will then be purified and characterized, and compared in assays using patient sera with conventionally produced SARS-CoV-2 spike proteins in collaboration with IME-TMP and the University Hospital Frankfurt.

As a proof of concept, production of a spike protein at the 50 kg scale will be carried out to provide urgently needed assay reagents for the manufacture of immunological rapid tests. This will support the “clearance testing” of individuals, thereby enabling a gradual relaxation of pandemic-related restrictions.