Japanese pharma subsidiary’s plant-based COVID vaccine is on the cusp of mass production

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

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

The final phase of clinical trials ended last year in six countries and, according to the firm, their results showed the vaccine to be 71% effective. In Canada, the company filed an application in December for authorization of the vaccine and aims to begin distribution by the end of March.

Clinical trials are also underway in Japan. It is expected to file for pharmaceutical approval with Japan’s Ministry of Health, Labor and Welfare this spring, with the goal of putting the vaccines into practice in fiscal year 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 a type of VLP vaccine, which delivers virus-like particles (VLPs) to the human body as antigens. VLPs, resulting from the genetic engineering of organisms, have an external structure mimicking that of viruses, as well as an identical size. Chicken eggs, E. coli bacteria and insect cells, among other objects, have been used to make VLP vaccines. The new attempt aims to use plant-based VLPs.

Viruses have a basic structure of DNA or RNA, constituting the genetic information, surrounded by a protein envelope. The coronavirus and influenza virus have a lipid membrane as their outer layer, or viral envelope, and spike proteins protrude from it. As the size and external structure of VLPs are nearly identical to those of viruses, they hold promise as highly effective vaccine antigens. Meanwhile, since they do not contain genetic material, there is no risk 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, using insect cells and yeast.

VLPs are created from plants using Nicotiana benthamiana plants, a close relative of tobacco and fast growing. The genetic information of coronavirus spike proteins is implemented in plants and temporary genetic engineering takes place. The genetic information is then decoded in leaf cells, creating proteins that accumulate as VLPs. After a culture of about a week, the leaves are harvested, the VLPs are extracted and purified to create the final material used in vaccines. As manufacturing takes place in large-scale factories, it is said that vaccines can be mass-produced in a short period of time, and they can be stored and transported in a refrigerated state (between 2 and 8 degrees Celsius ) . While messenger RNA (mRNA) vaccines, which were first put into practice 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.

Plant-based vaccine manufacturing technology also has the potential to be used in various fields by modifying the genetic code of plants. Medicago has also embarked on the research and development of vaccines against seasonal influenza, as well as against the rotavirus and norovirus responsible for the stomach flu. By taking advantage of the rapid growth of plants, it is hoped that plant-based vaccines can become a rapid response option to fight pandemics. The technology would begin to be introduced to deal with the global spread of the omicron variant.

(Japanese original by Tomoko Mimata, Department of Science and Environmental News)