Update (November 11, 2020): Quebec-based biopharmaceutical company Medicago has announced positive results from a Phase I trial of its candidate plant-derived vaccine. Interim results of the trial show that all participants developed an antibody response after two doses of the COVID-19 adjuvanted vaccine candidate.
“These are very promising results. After two doses, the adjuvanted vaccine candidate induced robust neutralizing antibody and cellular immune responses which is encouraging and support further clinical evaluation,” said Nathalie Landry, executive vice president, Scientific and Medical Affairs at Medicago in a press release from the company.
“We also observed that the antibody levels were higher after vaccination than those observed in convalescent sera from people who recovered from the disease,” said Landry.
While Medicago did not release full safety data, it said side effects were generally mild to moderate and short in duration.
Announcement of the positive vaccine trial data follows on the heels of Pfizer and BioNTech’s promising vaccine results, which showed 90 percent effectiveness in participants that contracted COVID-19.
The Canadian federal government has pledged $173 million in funding to Medicago for its vaccine research and development, as well as for the construction of its Quebec City manufacturing facility. It has also signed a deal with the company to secure the rights to purchasing 76 million doses of the vaccine.
The recombinant Coronavirus Virus-Like Particle (CoVLP) vaccine candidate was evaluated both alone and with two different adjuvants in a prime-boost regimen — GSK’s proprietary pandemic adjuvant technology and Dynavax’s CpG 1018. Adjuvants are used to help stimulate stronger vaccine immune responses. For example, CpG 1018 promotes development of the Th1 subset of helper T cells by targeting toll-like receptor 9 (TLR9). Adjuvants potentially reduce the amount of antigen required in a single dose of a vaccine, allowing for more people to be vaccinated, which is particularly important during a pandemic.
According to Medicago, significant humoral and cell-mediated immune responses were achieved with both adjuvants. Based on the encouraging Phase I data, Medicago says it plans to proceed with its Phase II/III trials.
Data from the interim analysis have been published on the online preprint server medRxiv.org.
Originally published on July 15, 2020:
Quebec-based biotechnology company Medicago has developed a plant-derived vaccine for COVID-19 that is now undergoing early-stage clinical trials.
The Phase I trials will evaluate the safety of the plant-based vaccine in a cohort of 180 healthy men and women between the ages of 18 and 55. The first trials began in Quebec City on Monday.
Medicago’s candidate product is among the first plant-based vaccines being tested for COVID-19.
Currently, around 20 vaccines are undergoing human trials around the world, including ones from Moderna and Pfizer, which have demonstrated positive preliminary results. Medicago is also planning a Phase II/III trial slated to begin in October.
The randomized, partially blinded Phase I study will test the safety and dosing of the vaccine. Dosages of 3.75, 7.5 or 15 micrograms of the recombinant Coronavirus Virus-Like Particle (CoVLP) vaccine candidate will be evaluated alone or with an adjuvant in a prime-boost regimen. Medicago will be testing its vaccine candidate with adjuvants from GlaxoSmithKline, the world’s largest vaccine maker, and Dynavax Technologies Corp.
According to Medicago, “an adjuvant can be of particular importance in a pandemic situation as it may boost the immune response and reduce the amount of antigen required per dose, allowing more vaccine doses to be produced and therefore contributing to protect the greatest number of people.”
Plant-Based Vaccine Technology
Traditional methods to make vaccines involve the use of animal products or live viruses. Typically, vaccine development involves the use of chicken eggs to propagate a virus. However, Medicago’s plant-based design uses living plants as the viral host instead of an animal.
The genetic sequence of a virus is generated using recombinant technology and the resulting virus-like particles (VLP) mimic the shape and dimensions of a virus, which the body recognizes as being foreign and elicits an immune response against. For COVID-19, the technology is used to generate fragments of the spike protein of the SARS-CoV-2 novel coronavirus, which the virus uses to latch onto and enter host cells.
Bruce Clark, president and CEO of Medicago said the “plant-based approach is significantly faster and offers more consistent results than egg-based or cell-based methods.”
While it takes five to six months to propagate a virus in eggs, the plant-based technique requires just five to six weeks, he says.
This is because Medicago’s VLPs are grown in the hardy Australian weed, Nicotiana benthamiana, which is a relative of the tobacco plant. Given that weeds grow fast, genetic material from the virus is incorporated into the leaves, using a de-fanged bacterium that infects plants, when the plant is five to six weeks old. In effect, VLPs can be found in high concentrations in the cells of the leaves just six to nine days after incubation, and are fairly easy to harvest and extract.
Moreover, Clark says viruses are prone to mutations as they adapt and grow in an egg, which could result in a vaccine that doesn’t exactly match the circulating virus. In contrast, “a plant is a plant,” he says, making production easily scalable.
Medicago has used the same technique for developing a seasonal flu vaccine candidate, which is currently undergoing review by Health Canada. If approved, Clark says it would be the first plant-based vaccine in the world.
“We are thrilled to see our COVID-19 vaccine candidate enter the Phase I trial, and we look forward to obtaining safety and immunogenicity results in October,” said Nathalie Landry, Executive Vice-President, Scientific and Medical Affairs at Medicago in a press release from the company. “Our progress continues to demonstrate the value of Medicago’s unique plant-based vaccine technology.”
Medicago’s vaccine is among hundreds being currently developed worldwide for COVID-19.
Guided Caution and Distribution
Amidst the raging global vaccine race, Clark voices caution however, that any product, including that of his company, should not be overplayed in saving the world from the ongoing global pandemic. These kinds of expectations are not only unrealistic, but also pose harm if vaccines are not developed or tested effectively out of growing urgency.
“Whatever vaccine we get in this first round – unless it’s a miracle – it’s not going to be perfect,” says Clark. “It’s going to have to undergo development, it’s going to take probably years to come up with an understanding of the right vaccine, the right approach. It’s not the panacea.”
“To assume that we can have, in 18 months, the solution to a pandemic that comes around once in a generation, is naïve,” he adds.
Most experts agree that no one vaccine will be the magic bullet for beating COVID-19, with respect to both supply and efficacy.
Medicago says if trials for its vaccine are successful, it expects to be able to produce approximately 100 million doses of the vaccine by the end of 2021, and up to one billion doses annually by the end of 2023 at its proposed production plant.
Medicago has the added pressure of completing construction of a large-scale manufacturing facility in its home base of Quebec City. A Canadian plant is certainly needed as US-Canadian borders remain closed and current US policies prioritize distribution of COVID-19 supplies to its domestic market.
Despite this, meeting global demand would require multiple manufacturers, multiple distribution routes and lots of co-operation, says Clark. “There has to be some ability to share those around and distribute, whether that’s through an entity like the WHO, or something equivalent.”