In the battle against COVID-19, the goal of a safe and effective vaccine has often seemed a distant prize.
But for a handful of Canadians, the promise associated with that prize is now at hand.
On Monday, six volunteers rolled up their sleeves to receive shots at a study site operated by Syneos Health in Quebec City, officially launching the first Canadian clinical trial of any COVID-19 vaccine.
The vaccine, developed by Medicago Inc., a Quebec biopharmaceutical company, has shown positive results in animal studies. But this is its first test in humans.
“It’s an exciting day for us,” said Nathalie Landry, the company’s executive vice-president of scientific and medical affairs. “We’re hoping to be part of the solution to COVID-19 disease.”
The trial is an early stage test of the vaccine’s safety, though not its efficacy. For the next three days, the volunteers will be monitored and their response to the vaccine assessed. If nothing looks amiss, the next group of volunteers will be called in and the process will continue with up to 180 subjects receiving the vaccine either at the Quebec City site or at a second location in Montreal. The participants, who include both women and men between the ages of 18 and 55, will receive a second dose of the vaccine three weeks after the first.
See Chart: How COVID-19 Vaccines Work https://www.theglobeandmail.com/files/graphics/0713-nw-na-vaccine-folio/0713-nw-na-vaccine-folio-desktop.png?token=0
The trial is randomized so that participants will receive the vaccine in one of three dosages and with or without one of two adjuvants. The adjuvants are compounds that are delivered together with the vaccine to act as a general alert that can help stimulate the body’s immune response.
While there is no guarantee that any of the combinations will provide protection against the coronavirus, there has been no shortage of people looking to participate. “It’s not very difficult these days to find volunteers for a COVID-19 vaccine,” Dr. Landry said.Whatever the outcome, the trial is a key milestone for the company, which has developed a made-in-Canada technology for rapidly scaling up vaccine production in plants, instead of in cell cultures as is the case for many vaccines.
The effort adds to the roughly 180 COVID-19 vaccines in development around the world, some of which have proceeded to advanced-stage trials involving thousands of subjects.
But with the possibility that any of these front-runners may ultimately fail, or that Canada will be unable to secure its own supply ahead of other countries, experts stress the need for home-grown options.
“Hopefully we’ll have multiple successes within Canada so that there are multiple manufacturers with the capability of supplying Canadian requirements,” said Scott Halperin, director of the Canadian Centre for Vaccinology in Halifax.
FIRST AMONG EQUALS
Until this week it was not certain that Medicago’s vaccine would be the first one to reach human trials in Canada. For more than a month, another clinical trial planned by Dr. Halperin and colleagues has been poised to start in Halifax and appeared likely to be the first Canadian-based trial out of the gate. That trial is intended to be larger than Medicago’s and is aimed at identifying optimal dose levels.
The candidate vaccine from CanSino Biologics, a Chinese company that is collaborating with Canada’s National Research Council, has already been been tested in an initial clinical trial in Wuhan, with results published in May.
China has since announced that the vaccine has been approved for use by its military, despite its experimental status. On Saturday, CanSino said it is in talks with Brazil, Chile, Russia and Saudi Arabia about holding larger-scale trials. But delivery of the vaccine to Halifax for the Canadian trial has been held up by Chinese customs authorities. Dr. Halperin said he did not know the reason for the delay.
“It’s part of whatever process China is making for any vaccines that they produce,” he said. “We have no insight into how that process goes.”
He added that the Halifax trial remains ready to go as soon as the vaccine arrives.
The worry lurking in the background is that the delay is a harbinger of what lies ahead as various vaccine candidates begin coming online and international partnerships come up against domestic plans and priorities.
Medicago’s vaccine can be produced in Canada. However, when scaling up to larger trials, it will need to rely on its production facility in North Carolina.
Meanwhile, IMV Inc., a Nova Scotia company, has said it is also on track to begin clinical trials in Canada this summer, pending Health Canada approval. Like others in the vaccine race, the company is leveraging a technology that was originally developed to fight another virus. But its approach has long focused on the immune systems of older patients, a key risk group for COVID-19.
“When it became clear that the coronavirus was hitting the elderly, that’s when we said we have something unique here,” said Marianne Stanford, IMV’s vice-president of research.
VIDO-InterVac in Saskatchewan, one of Canada’s largest infectious disease centres and the first in the country to successfully isolate the virus that causes COVID-19, may come next with a vaccine candidate the centre says could be ready for human trials by October. Edmonton-based Entos Pharmaceuticals has also announced plans to proceed with a trial of a vaccine that it hopes may be broadly effective against a range of coronaviruses, based on work led by chief executive and University of Alberta researcher John Lewis.
While some candidates have taken longer to develop than others, researchers say the field remains wide open in terms of which Canadian vaccine, if any, is most likely to make it to a Phase 3 clinical, a study that would be conducted at a large enough scale to show that the vaccine is beneficial.
“My hope is that at least a quarter to a third of them will look good enough to get to Phase 3,” Dr. Halperin said.
RECOGNIZING THE ENEMY
The rush to develop a COVID-19 vaccine began in earnest in mid-January when Chinese researchers published the genome of the SARS-like virus behind the pandemic. That provided researchers with the blueprint for recreating the spike proteins that protrude from the coronavirus and serve as its unique calling card.
The goal for any vaccine is to teach the immune system to recognize the most distinctive bits of the protein so that it knows COVID-19 is something that it needs to fight. The vaccine does this by delivering the incriminating material to a part of the immune system called antigen-presenting cells. The cells engulf what they perceive to be an invader and break it down into representative pieces which are shown to other immune cells rather like a “Wanted!” poster. Some cells will then go on to produce antibodies to intercept and block coronavirus spike proteins. Others more directly seek out and destroy anything that displays the same telltale structure.
A traditional approach to vaccine development is to use a weakened or inactivated form of the virus to train the immune system to recognize its enemy. Medicago’s strategy is to replace the virus altogether with an imposter known as a “virus-like particle.” From the outside, the particle resembles the genuine virus, including its surrounding mantle of spike proteins. But inside there is no genetic material that the virus needs to replicate. The immune system doesn’t know this and responds as though it is seeing the genuine article.
Genetic instructions for making the particles are provided to a plant – a relative of tobacco – which dutifully churns out the particles as though it were making something required by its own metabolism. The ruse works for only a week or so, Dr. Landry said, after which “we harvest, crush up the leaves and purify the vaccine.”
While virus-like particles have already led to a successful vaccine for human papillomavirus (HPV), the CanSino approach is makings its debut in humans with COVID-19. The vaccine is delivered by another type of virus altogether, in this case an adenovirus, with DNA that has been altered so that it covers itself in coronavirus spike proteins. Once again, the immune system is fooled and reacts to the adenovirus, which does not replicate inside host cells, as if it were a COVID-19 infection.
In addition to CanSino, both Oxford University and pharma giant Johnson and Johnson are moving rapidly to develop adenovirus vaccines for the coronavirus.
In Canada, IMV and VIDO-Intervac are working on different types of vaccines that both aim to deliver pieces of coronavirus protein directly to antigen-presenting cells. The advantage of the approach is that it is easier to scale up vaccine production by synthesizing the proteins without an elaborate system for delivering them.
Volker Gerdts, VIDO-InterVac’s CEO, said the Saskatoon centre’s vaccine candidate has taken longer to develop because it is using an adjuvant that is new to human trials and therefore requires more testing. But in the end, he said, “we think our vaccine will be better.”
Another approach that is having its debut in humans is an RNA vaccine developed by Massachusetts-based Moderna Therapeutics. It takes the process one step further by providing host cells with instructions for making proteins rather than the proteins themselves. That strategy has put Moderna among the leaders in the global vaccine race. But it remains to be seen whether those who reach the finish line first in making a vaccine will have the most effective product in the long run.
This is why scientists and companies still working on vaccines at earlier stages of development see no reason to stop. Because of the scope of the COVID-19 pandemic and its global economic impact, it’s possible, even likely, that several vaccines will be needed to address all populations and regions on a timeline that can allow the world to move forward from its pandemic status.
For many of those involved in the hunt, the quest has been both exhausting and exhilarating, with a scientific legacy that will leave the field forever transformed and a host of personal experiences that few researchers, if any, would have expected six months ago.
“How do you develop a vaccine in the middle of a pandemic? It’s been interesting,” IMV’s Dr. Stanford said. “We have scientists trying to do work while home schooling and also trying to keep it down to five people in the lab at once. You could write a book after all this is done.”
https://www.theglobeandmail.com/canada/article-first-canadian-clinical-trial-of-any-covid-19-vaccine-is-launched-in/
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