Immunologists, epidemiologists, mathematicians, engineers… A variety of scientists worldwide are changing their primary research focus these days with the aim to bring solutions for the devastating SARS-CoV-2 pandemic. Plant researchers are no different.

The CSIC researchers at CRAG María Coca and Juan José López-Moya are proposing to use their expertise in plant biotechnology and virology, respectively, to produce SARS-CoV-2 antigens that could be used as vaccines. Coca and López-Moya propose to experiment with different expression systems deriving from plants and they have assembled a team with colleagues from other research centres (CNB, IBMCP, CEBAS) which includes an immunology expert in coronavirus that would perform the validation studies in mice and in cell cultures.

“The production systems we propose would overcome some of the problems associated with other vaccine production systems, such as the difficulties to escalate production, or the need to isolate the antigen and to purify it. Plant systems are also free of other human pathogens, and, the production would be safe at a much lower cost in terms of time and money”, explains María Coca.

Plants as economical biofactories

Humans have relied on plants to cure diseases since ancient times. Modern pharmacotherapy includes many drugs whose active compounds were initially discovered in plants, and wild plants are still under investigation in the hope to find new bioactive compounds. In this sense, the ability of plants to synthetize a wide range of molecules is well known.

Thanks to the modern biotechnological tools, nowadays researchers can engineer plants to produce other compounds of interest such as antimicrobials. In 2019, María Coca, together with the expert on plant viruses from the IBMCP José Antonio Darós, already demonstrated that they can produce active antifungal compounds in Nicotiana benthamiana plants. To do so, they engineered a plant virus to produce antifungal proteins inside the plant leaves. This same strategy could be now used to produce SARS-CoV-2 antigens, not only in N. benthamiana, but also in lettuce plants.

“Once the system is developed and validated, it would be very easy to implement it for antigen production”, explains López-Moya.

“With its adaptation to lettuce, we could even test for oral immunization”, adds Coca.

Among many other advantages, it is worth noting that plants can be grown easily in developing countries that lack sophisticated protein production methods, therefore contributing with large-scale solutions to this global crisis.

CRAG researchers have experience also in the adaptation of plant-derived technologies to other platforms that can be adapted for the production of SARS-CoV-2 antigens, such as fast-growing yeast cultures where they have successfully produced antifungal compounds. With these approaches, SARS-CoV-2 antigens could be produced in a matter of days at industrial scales.

Related to this, in collaboration with the biotechnology company Vytrus biotech, these CRAG researchers are currently engaged in pushing the limits of the technology to adapt natural plant properties to enhance the immunogenic response and facilitate antigen stability and delivery.