COVID-19 vaccine: Medicago harnesses 'unique' virus trick to get one step closer to breakthrough

Prime Minister Justin Trudeau has stressed to Canadians there could be several “recurrences” of COVID-19 until there is a vaccine for the virus. Medicago, a biopharmaceutical company based in Quebec, is working on developing the vaccine that the prime minister indicated is critically important.

On Thursday, the company announced its vaccine candidate has shown a positive antibody response in mice and will move towards human clinical trials by the summer.

“These positive results are pivotal to initiate a clinical study in healthy volunteers,” Nathalie Landry, executive vice-president of scientific and medical affairs at Medicago said in a statement.

“Once results from a second ‘boost’ dose are available, Medicago will submit a clinical trial application to Health Canada and an investigational new drug submission with the FDA in the United States to allow for the initiation of human clinical trials this summer.”

Medicago estimates its current facilities in Quebec and North Carolina could produce up to 20 million and 100 million doses, respectively, of pharmaceutical-grade COVID-19 vaccines for 2022. It has also indicated “millions of doses” could be available “by the end of the year as needed.”

The company works with plant-based technology, using a plant called Nicotiana benthamiana, to produce vaccines and monocle antibodies. In March, it was announced the company was able to successfully produce a virus-like particle (VLP) of the coronavirus 20 days after receiving the SARS-CoV-2 gene, the first step in vaccine development.

“We were able to take the sequences that we thought would be most interesting, that targeted the spike protein, which is probably the most important viral protein for causing infection,” Brian Ward, medical officer for Medicago and a professor at McGill University, told Yahoo Canada last month.

“It faithfully reproduced the viral spike protein in a way that...maintained that spike protein in a form that was likely to cause the immune system to react in a good way, to produce antibodies that would neutralize the real virus and cellular immunity that would help clear the virus from infected cells.”

Ward added these tiny virus-like particles are about the same size and shape as the virus itself, and if the immune system reacts to them the same way it does to the influenza-like particles produced by the company in the past, they will trick the cells into thinking they’re real viruses.

What makes this plant-based technology particularly effective?

Although virus-like particles can be developed in other systems, Ward indicates what is notably “unique” about Medicago’s production system is the plant is also the bioreactor, instead of having a stainless steel tank with a cell that is producing the protein. In this case, the plant itself is producing the protein, which positively impacts the “scalability” of the development.

“You can generate huge amounts of what we call biomass, just basically the green leaves, that then go into a relatively small, if you will, pharmaceutical manufacturing set of rooms and what comes out the other side is a highly purified virus-like particle,” he said.

“Our upstream is, in a sense, much simpler because it’s basically a greenhouse, and the downstream is really very similar to the other manufacturing processes. What that means is that you can plant a few thousand more plants in greenhouses but it’s kind of hard to go out and buy a one thousand litre steel bioreactor, with all of the controls that are necessary.”

Ward also indicates plant cell membranes themselves are able to give an extra “oomph” to the vaccines, as they are able to interact with the human immune system.

“The plant cell membranes themselves appear to be able to interact a little bit with the human immune system and promote immune responses that are beneficial, particularly for viruses,” Ward said. “We get...a little bit of extra stimulation from the presence of the plant-like o lipids that are in our vaccine but not necessarily in other vaccines.”

Healthcare workers at St. Paul's Hospital acknowledge applause and cheers from people outside the hospital, as a convoy of first responders with lights and sirens activated parade past to show support for the hospital staff, in Vancouver, British Columbia, Sunday, April 5, 2020. (Darryl Dyck/The Canadian Press via AP)

What outstanding questions are there about COVID-19 that will impact the development of a vaccine?

As Medicago continues their work on the development of a vaccine for COVID-19, there are still some questions about the virus that will be particularly influential in the progression of the company’s work.

Ward said one aspect is the lack of clarity on what the best immune response is how and long it lasts for coronaviruses generally, but it’s believed that cellular immunity is quite important for COVID-19, as it is for other viruses.

“We know that the antibodies that people develop for COVID-19 are actually pretty short-lived. You get a burst of antibodies and then they tend to go away,” Medicago’s medical officer said. 

Ward also indicated it is not clear what will happen to the mutation of the virus as more people either become infected or exposed through a vaccine, and if it will start to mutate faster.

Another possible concern is the vaccine could have a negative effect on humans, leading to a “vaccine-enhanced disease.”

“This phenomenon, vaccine-enhanced disease, has been seen with other vaccines...much more recently with the dengue vaccine, [Dengvaxia],” Ward said. “Even as we’re rushing forward to introduce vaccines we do have to be aware that we also don’t want to do something bad.”