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COVID vaccines grow on leaves

Canadian regulators have started a rolling review of a plant-made COVID-19 vaccine that has produced strong immune responses in a mid-stage clinical trial. Medicago, based in Quebec City, Canada, announced that after two doses, its vaccine candidate, mixed with GlaxoSmithKline’s pandemic oil-based adjuvant AS03, met its goals in a phase 2 study. In the randomized, placebo controlled trial, after two doses of the vaccine, known as CoVLP, generated neutralizing antibody responses that were about ten times higher than in patients recovering from the virus. In addition, the vaccine stimulates a cellular immune response of the T helper-2 type (producing interferon-γ and interleukin-4), unlike other COVID-19 vaccines, which stimulate a T helper-1 response. The vaccine was well tolerated, with adverse effects mild to moderate. Medicago is arriving late to the pandemic vaccine response, but plant-based production holds the advantage that it can be rapidly scaled up and the vaccine, stored between 2 and 8 degrees Celsius, may be useful in varied environments. Results from phase 1 trials were published 18 May.

Medicago’s platform uses living Nicotiana benthamiana, a relative of tobacco, as a bioreactor to manufacture non-infectious coronavirus-like-particles (CoVLPs). The plants are not genetically modified but transfected with full-length SARS-CoV-2 spike glycoprotein. The recombinant virus-like-particles self-assemble and bud off the plant cell surface, accumulating in the space between the plasma membrane and the cell wall. The leaves are blended to extract and purify the VLPs for use in the vaccine. The recombinant VLPs are non-infectious because they lack the virus’s core genetic material, but still stimulate an immune response similar to that seen in a natural infection.

A phase 3 trial of the vaccine launched in March 2021, and a trial to test the vaccine against emerging variants has also begun. Medicago is jointly owned by Mitsubishi Tanabe Pharma and Philip Morris International.

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COVID vaccines grow on leaves. Nat Biotechnol 39, 649 (2021).

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