Plants- The New COVID19 Vaccine Manufacturers

Remember how we were taught in school that plants provide us with food, oxygen, rain, and shelter? Well, get ready to teach the new generation about the newest addition to that list! While we witnessed the emergence of new and rapid vaccine production during the COVID-19 pandemic using viral vectors (Sputnjik, AstraZeneca) and mRNA vaccines (Pfizer, Moderna), researchers are still enthusiastically developing newer vaccine technologies for COVID-19 to cope up with the global vaccine demand. Speaking of, from a Canadian biotech firm- Medicago, Nature Medicine brought us some reports about the clinical trial of a plant-produced virus-like particle (VLP) vaccine candidate for COVID19.

Ward and colleagues from Research Institute of the McGill University Health Centre and Medicago recently carried out the Phase I trial of CoVLP (COVID-19 virus like particle) derived from a plant. 180 participants (18-55 years of age) were divided into study groups of 20 people each and administered with two doses of CoVLP with either of the three different concentrations (3.75 mg, 7.5 ug or 15 ug); with or without an adjuvant. The adjuvants used in this study were AS03, which induces a balanced Th1/Th2 response; and CpG1018, which targets toll-like receptor 9 as well as induces Th1 response. This first report is vital to evaluate the safety, tolerability, and immunogenicity of different vaccine doses and adjuvants.

Adverse effects to the vaccine administration were mostly mild to moderate, the most common being pain at the site of injection, followed by headache and fatigue. All adverse effects were resolved in 1-4 days. Although groups that received vaccines with adjuvants experienced higher incidences of headache and fatigue, they also produced a more robust immune response compared to CoVLP alone. Immune responses against different concentrations of CoVLPs only were low and inconsistent. However, in combination with the adjuvants, IgG levels were readily detected after only the first dose. After the second dose, CpG1018-adjuvanted groups had 8- to 18-fold rise in the total IgGs, and AS03-adjuvanted groups had between 28- and 92-fold rise. On comparing adjuvants, AS03-conjugated vaccines had more localized and systemic adverse effects than CpG1018-conjugated vaccines. On the other hand, maybe because AS03-conjugated vaccine induced higher specific IgGs and neutralizing antibodies response against the spike protein, it showed substantially greater recovery as compared to unvaccinated immune response against natural COVID-19 infection.

How is CoVLP made in plants?

‘Medicago’s plant-based production platform’ uses transfection of a native Australian tobacco plant, Nicotiana benthamiana, with a plant tumor causing bacteria, Agrobacterium tumifaciens. This plant pathogen acts as a vector to express the full-length S glycoprotein of SARS-CoV-2. The vector cuts a defined DNA segment from the plasmid and transfers it to the nucleus of the plant cells. That segment stays episomal (extrachromosomal genetic element which can replicate) and expresses the S glycoprotein before being degraded. The protein self-configure to form VLPs which get accumulated between the plasma membrane and cell wall, from where it is isolated and purified.

While little is known to us, there are already a few successful plant-based platforms for biotherapeutics production:  taliglucerase alpha, developed by Protalix and Pfizer, was the first FDA-approved plant-based medication to treat Gaucher’s disease; and certain monoclonal antibodies for Ebola are also manufactured in plants. On the other hand, VLP vaccines have also been on trial for diseases such as avian (monovalent) and seasonal (quadrivalent) influenza.

With below moderate adverse effects, we can confirm the safety of this vaccine candidate and agree that CoVLP with AS03 as adjuvant presents the best plant-derived vaccine option for further trials. Antibuddies look forward to reports on the phase 2/3 efficacy trial of CoVLP-AS03, which is going to be a global study including 11 countries. That will result in bigger demographic characteristics compared to phase 1 with Caucasians as the dominant population. It will be interesting if effective results are obtained from bigger groups instead of 20 participants.

What do you think? Would you get your vaccine from a plant? Stay tuned to our blog to learn more!

Source: Ward BJ, Gobeil P, Séguin A, Atkins J, Boulay I, Charbonneau PY, Couture M, D’Aoust MA, Dhaliwall J, Finkle C, Hager K, Mahmood A, Makarkov A, Cheng MP, Pillet S, Schimke P, St-Martin S, Trépanier S, Landry N. Phase 1 randomized trial of a plant-derived virus-like particle vaccine for COVID-19. Nat Med. 2021 Jun;27(6):1071-1078. doi: 10.1038/s41591-021-01370-1.

Article author: Ines Poljak. Ines is a MSc student at University of Copenhangen and works on multiple myeloma bone disease. She worked in several clinical laboratories before committing herself completely to research.

Editor: Sutonuka Bhar. Sutonuka is a PhD candidate at the University of Florida. Her work focuses on host immune responses against viruses and bacterial membrane vesicles.

Check out Antibuddies’ blog post “Plants- The New COVID19 Vaccine Manufacturers”.

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