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Japanese pharma subsidiary's plant-based COVID vaccine on cusp of mass production

A plant factory where Medicago Inc.'s COVID-19 vaccines are manufactured is seen in this image provided by Mitsubishi Tanabe Pharma Corp.

TOKYO -- A biopharmaceutical company is seeking approval in Canada for the world's first plant-based COVID-19 vaccine, sparking hopes for mass production in the near term.

    The vaccine employs the mechanism of having plants create virus-like particles, which are extracted from the crops grown in greenhouses and presented as antigens. If the plant-derived vaccine for human use, currently under research and development by Medicago Inc., a Canadian subsidiary of Japan's Mitsubishi Tanabe Pharma Corp., is put to practical use, it will be the world's first such vaccine.

    The final phase of clinical trials was finished last year in six countries, and according to the firm, their results showed the vaccine had 71% efficacy. In Canada, the company filed an application in December for the vaccine's authorization, and aims to start distribution by the end of March.

    Clinical trials are also being carried out in Japan. There are plans to file an application for pharmaceutical approval with Japan's Ministry of Health, Labor and Welfare this spring, with the goal of putting the vaccines to practical use within fiscal 2022.

    Vaccines contain pathogens, parts of them or other substances to induce an immune response against infectious diseases in the body. Medicago's vaccine is one type of VLP vaccine, which administers virus-like particles (VLPs) to the human body as antigens. The VLPs, created through the genetic engineering of organisms, have an external structure mimicking that of viruses, as well as an identical size. Hen's eggs, E. coli bacteria and insect cells, among other objects, have been used to manufacture VLP vaccines. The new attempt aims to make use of plant-based VLPs.

    Viruses have a basic structure of DNA or RNA, constituting genetic information, surrounded by a protein shell. The coronavirus and influenza virus have a lipid membrane as its external layer, or viral envelope, and spike proteins protrude from them. As VLPs' size and external structure are almost identical to that of viruses, they are promising as highly effective vaccine antigens. Meanwhile, as they do not hold genetic material inside, there are no concerns of viruses proliferating in the body after vaccination. This VLP vaccine technology has already been used for HPV, which is a cause of cervical cancer, by using insect cells and yeast.

    VLPs are created from plants by using Nicotiana benthamiana plants, a species that is a close relative of tobacco and has quick growth. The genetic information of coronavirus spike proteins is implemented into the plants and a temporary genetic engineering takes place. The genetic information is then decoded within the leaves' cells, creating protein that accumulate as VLPs. Following cultivation of around one week, the leaves are harvested, VLPs are extracted from them, and purified to create the final material used in vaccines. As manufacturing takes place in large-scale plant factories, it is said that the vaccines can be mass-produced within a short period of time, and that they can be stored and transported in a state of refrigeration (between 2 and 8 degrees Celsius). While messenger RNA (mRNA) vaccines, which were put to practical use for the first time amid the spread of the coronavirus, require storage at ultra-low freezing temperatures, the plant-based vaccine has the advantage of being easy to handle.

    The manufacturing technology of plant-based vaccines also has the potential to be utilized in various fields by changing the genetic code of plants. Medicago has also set about research and development of vaccines for seasonal influenza, as well as the stomach flu-inducing rotavirus and norovirus. By taking advantage of plants' fast growth, it's hoped that plant-based vaccines can become a quick-response option for fighting pandemics. The technology is reportedly beginning to be introduced to deal with the global spread of the omicron variant.

    (Japanese original by Tomoko Mimata, Science & Environment News Department)

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