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What you need to know about COVID-19: August 7, 2020
The pathogen that causes COVID-19 looks for human cells where it can latch on. It seeks out and finds them in our airways, using “spikes,” or proteins, on the outer surface of the virus.
When a virus particle finds its way onto a cell, the spike protein clamps on and changes its shape. It morphs from looking like a club, to looking like a spear.
Once it fuses with the cell membrane, the viral RNA — its genetic material — enters the cell, Dr. Brian Ward explains, where it replicates, making copies of itself, which then exit to infect other cells. Or spread to the next human.
Ward is a professor in McGill University’s department of medicine. He is also the chief medical officer for Medicago Inc. , a Quebec-based firm that’s using plants to produce a vaccine against the pandemic virus now churning across the globe.
On Jan. 10, 33 days after the first case of a pneumonia of unknown origin was reported in Wuhan, in China’s Hubei province, Chinese scientists published the genetic blueprint, the genomic sequence, for SAR-CoV-2 — the virus causing COVID-19. One day later, Medicago, like everyone else, was able to access that information, joining what has become a historic sprint to find a vaccine. Twenty days after the genome was published, Medicago scientists scored a major hit, producing a virus-like particle, or VLP, that mimics the structure of the virus, but stripped of any harmful genetic material inside, making them non-infectious, but able to trick the immune system into thinking it’s “seeing” a virus, and hopefully generate enough antibodies so that when the person encounters the real virus, they’re protected.
The company hopes to begin testing their candidate vaccine in humans in July, possibly sooner.
“Typically, the first in-human study tends to be quite small, 40 or 50 people,” Ward says. “But pretty much everybody is bending the rules to try to move faster. So many of the vaccine companies that are moving their candidates towards clinical trials are talking about doing much larger studies to address all of the questions that need to be addressed at once.”
Typically, the first in-human study tends to be quite small, 40 or 50 people. But pretty much everybody is bending the rules to try to move faster
What dose should you use? How many doses do you need? Two? Three? Do you get any benefit from having an adjuvant, an additive that can boost responses? Normally, scientists answer those questions sequentially, one at a time. No one has time for that. As of Friday, the virus, for which there is no known cure, no proven treatment, no crucial vaccine, had infected more than half a million people globally, killing nearly 25,000. Doctors and other healthcare people are preparing living wills and end-of-life plans, worried they won’t come out of this. There are fears Canada could soon be hit with a “tidal wave” of severe respiratory illness caused by COVID-19. On Tuesday, a 16-year-old French schoolgirl, identified only as Julie, died in a Paris hospital, becoming the youngest person in the country to die from COVID-19. She was perfectly healthy before she contracted the virus. So it comes down to a process of negotiations with regulators — what do people consider safe?
“Obviously the first human studies are done in young, healthy people, where they are the least likely to get into trouble if anything goes wrong, with any of the vaccines, including ours,” Ward says. “We want to move forward in a very careful, deliberate way. But you have older people and people with respiratory and cardiac diseases who are dying at stunningly high rates when they get infected — we’re talking 15, 25, 28 per cent mortality.”
Vaccines are one of the greatest successes in the history of public health, but it’s a history not without its controversies. They haven’t been forgotten in the scramble to find effective vaccines against a virus that, until recently, no human had ever been exposed to before. Dozens of labs around the globe are working feverishly to find something that could be safely used to potentially dose hundreds of millions, possibly even billions, of people.
The best-case scenario is that a vaccine, or several vaccines, becomes available before a second wave hits, in the fall or early spring. The worst-case? The vaccines cause more severe disease.
Respiratory syncytial virus, or RSV, is the leading cause of lower respiratory tract infections in children. In the late ‘60s, babies and toddlers immunized with an inactivated virus against RSV experienced a phenomenon called “vaccine-enhanced disease.” Instead of being protected, they experienced a worse form of RSV, suffering high fever, wheezing and pneumonia, when they were exposed to the natural, wild type virus. That put a chill on the development of RSV vaccines that’s persisted to this day.
“We have some pretty good ideas about why those vaccine-enhanced diseases occurred and so we are quite specifically designing our vaccine to avoid that possibility,” Ward says.
There are always risks when designing something new, especially at this kind of breakneck speed. The faster you go the more risky things get. “It’s not just rushing the science, but rushing the manufacturing,” says bioethicist Arthur Caplan. This will probably be the biggest vaccine exposure of all time. “People are going to say you’ve got to be cautious, you’ve got to be cautious. But other people will say, ‘it seems to have worked in the study group — we gotta go.
“I think we have to go somewhat faster,” Caplan says, “because the real answer to this plague is vaccination.”
Medicago has received a $7 million grant from the Quebec government. This week, it also received a share (the actual amount is not yet finalized, the company says) of the $192 million Prime Minister Justin Trudeau announced to help create and produce vaccines. Others include Vancouver-based AbCellera, which is scouring blood samples of people who have recovered from COVID-19 to find naturally produced antibodies that could be used to treat the sick and prevent infection. The company hopes to start testing in humans in July. Ottawa has also promised $23 million for the University of Saskatchewan’s VIDO-InterVac infectious disease research facility, one of the largest of its kind in the world.
Massachusetts-based Moderna began their first human trials on a potential COVID-19 vaccine last week. The first results could come in a little over two months, Bloomberg reports. The company says that, while a commercially available vaccine isn’t likely doable for at least 12 to 18 months, it’s possible one could be released for emergency use in some people, including health-care workers, this fall.
Vaccines only work to control outbreaks if enough people get them to create herd immunity. In a study of how people in the U.S. might respond to an outbreak of smallpox, 40 per cent of those surveyed said they would not get vaccinated even if vaccines were made compulsory. “Compliance with public health measures during a public health emergency cannot be assumed,” reads Canada’s pandemic preparedness plan.
Things might be different with a virus that has upended the world.
Medicago’s virus-like particles are grown in a hardy Australian weed, Nicotiana benthamiana , a relative of the tobacco plant. Weeds grow fast. When the plants are five- to six-weeks old, genetic material is introduced into the leaves using a de-fanged bacterium that normally infects plants. After six to nine days of incubation, the VLP’s, those virus-like particles, can be found in abundant concentrations in most of the cells of the leaves. “So they’re relatively easy to harvest and purify,” Ward says.
The current timetable is mice in the next week or two, macaques in two to four weeks and then humans as early as the start of the summer.
It’s kind of pathetically funny that great vaccine work done by scientists with SARS and MERS, both times the taps were shut off
The COVID-19 virus seems remarkably genetically stable. But some viruses can drift with mutations. In some cases a new strain can emerge that starts romping through populations again. It can be a coin toss whether the “drift” causes a worse virus to humans, or a feebler one.
There are only a few “non-consequential” mutations between strains around the world, says Dr. Eric Arts, Canada Research Chair in HIV pathogenesis and viral control at Western University. He uses a gum ball analogy to explain why that matters: The CoV-2 virus has about as many strains as gumballs you can put in a cup. “Seasonal flu, gumballs in a mixing bowl. HIV-1 in Canada alone, gumballs in an Olympic-sized pool.”
We don’t have an effective vaccine to HIV, but we can produce a vaccine for seasonal flu every year. “This is a major reason why we can be hopeful in getting a successful vaccine against a bunch of gumballs that a crazy kid might stick in his mouth at once,” Arts says.
Some researchers are experimenting with a century-old tuberculosis vaccine, in the hope it will reduce severe illness and deaths. At Western, researchers are working off a vaccine developed by Dr. Yong Kang for MERS, or Middle East Respiratory Syndrome, which is similar to the pandemic virus now circling the planet.
“It’s kind of pathetically funny that great vaccine work done by scientists with SARS and MERS, both times the taps were shut off,” says Arts. “It’s hard to even get them into animal studies let alone clinical trials, because pretty well governments say, ‘well, this disease is gone, why are we funding it?’”
Things are different this time, Arts says. “It’s amazing. I’ve never seen in my life, in my career, this much focus and this much effort being put towards so many vaccine candidates for one disease.
“It’s fantastic. And I think some good will come out of this,” Arts says. “But nothing like this can happen in a time frame that some governments would like to see happen.”
The immediate future might be more of an attack-team approach, using vaccines as they become available to stamp out wildfires as they pop up “and you still practice quarantine like we’re essentially doing now,” Arts says.
There may be faster success finding treatments for severe disease, like antibody-based therapies that involve extracting blood from patients who have recovered, isolating their antibodies, purifying them, rapidly cloning and then mass producing them as a possible antidote.
“The public has to put a bit of faith and trust in us that nobody is trying to take short cuts where it is going to be more detrimental to the population than the disease itself,” Arts says.
“We’re so much more advanced in ethics and understanding toxicity than we were back in the ‘50s that I think there’s not a lot we need to worry about.
“We need to worry about all those that will succumb to this disease.”
Copyright Postmedia Network Inc., 2020