Canada has announced that it has signed deals with four U.S. companies to reserve millions of doses of COVID-19 vaccines under development in an effort to make sure Canadians are at “the front of the line” when a vaccine becomes available.
It also said it’s close to a deal with AstraZeneca, based in the United Kingdom.
All of the companies have received funding from the U.S. government’s Operation Warp Speed, which is investing billions of dollars to fast-track the development of promising vaccine candidates.
Canada will receive 20 million to 76 million doses of each vaccine, should any of them successfully make it through clinical trials and be approved by Health Canada.
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They’re among more than 150 vaccine candidates under development around the world.
While they have shown promising results in small-scale, early-stage clinical trials, even those most advanced candidates have only recently begun Phase 3 clinical trials to determine their effectiveness in preventing COVID-19, and there is no guarantee any of them will make it to market. That’s the crucial large-scale human trial that must demonstrate that the vaccine prevents the disease, and it’s the final stage before approval by government.
“What we don’t know, of course, is which vaccines are going to be effective,” Dr. Michael Gardam, medical director of infection prevention and control at Toronto’s Women’s College Hospital, said in an interview with CBC’s As It Happens.
“We don’t know which company ultimately is going to have the best vaccine and the safest vaccine.”
Gardam said the deals represent different types of vaccine from four different manufacturers. The federal government, he said, is “just kind of playing the field … to make sure they have a reasonable chance that one of these will be successful.”
Here’s a closer look at the four candidates.
Janssen Pharmaceutical Companies (Johnson & Johnson)
Headquarters: Raritan, N.J., U.S.
Type: Non-replicating viral vector
Doses reserved: Up to 38 million
Phase of development: Phase 1/2a trial started in July
How it works: This vaccine, made by a Johnson & Johnson subsidiary, is a new type of vaccine called a non-replicating viral vector. Unlike traditional vaccines made from viruses or parts of viruses, this vaccine uses only a piece of coronavirus DNA. The DNA contains instructions for making a coronavirus protein so that the human body can produce it and learn to recognize it.
The protein targeted by most COVID-19 vaccines, including this one, is called the spike protein or S-protein. It’s found on the outer surface of coronaviruses and is used by the virus to bind to and enter human cells.
In this case, the DNA with instructions for making the spike protein is carried into the body by a common cold virus called an adenovirus. The adenovirus has been genetically modified so it can’t replicate itself in the human body. However, because it’s a virus, it may generate a stronger immune response than the DNA alone and helps get the DNA into human cells, where the spike protein can be produced. One disadvantage of this type of vaccine is that some people may have immunity to some adenoviruses from catching colds, which may make the vaccine less effective.
Viral vector vaccines haven’t been approved for widespread use in humans, but 12 are in use for diseases in livestock.
Where it’s at: The company reported in July that its vaccine protected monkeys against the virus after a single shot. The company started a human Phase 1/2a trial in July in Belgium and the U.S, and it announced this week it is starting a Phase 2 trial in Spain, the Netherlands and Germany. It says it will conduct Phase 3 trials in Argentina, Brazil, Chile, Colombia and Mexico.
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Headquarters: Cambridge, Mass., U.S.
Doses reserved: Up to 56 million
Phase of development: Phase 3 clinical trial started in July
How it works: Moderna’s vaccine candidate is made from messenger RNA, a type of genetic material. Messenger RNA, or mRNA, is used by cells to translate instructions found in DNA to make proteins. In this case, the instructions tell a human cell how to make a stabilized version of the spike protein for SARS-CoV2. That introduces the protein into the body so immune cells can learn to recognize it and produce antibodies against it.
The mRNA is encapsulated in a liquid nanoparticle for injection into the body. The LNP “container” protects it from being degraded by enzymes and helps it enter cells, Moderna says.
The mRNA itself also generates an immune response. While mRNA vaccines have been under development and widely tested for many years, none have ever been approved for widespread human use.
Where it’s at: Moderna launched the first Phase 3 clinical trial in the U.S. in July, and hopes to enrol 30,000 volunteers. The company reported in May that the vaccine produced protective antibodies in a small group of healthy volunteers, and the study showed the vaccine was safe. However, three people in an early-stage trial reportedly had severe or “systemic” adverse reactions, such as high fevers, to a high dose of the vaccine.
WATCH | Fast-tracking a COVID-19 vaccine is not without controversy:
Headquarters: Gaithersburg, Md., U.S.
Vaccine type: Protein subunit
Doses reserved: 76 million
Phase of development: Phase 1/2 clinical trial started in May
How it works: Novavax’s vaccine is the most traditional of the ones reserved by the federal government. The vaccine is made from nanoparticles of a key protein from the coronavirus that causes COVID-19. When the protein particles are injected into the body with an adjuvant — a compound that enhances the body’s immune response — the body learns to recognize and fight off the virus.
“That is a tried and true way of producing vaccines and of creating immunity,” Dr. Barry Pakes, a professor at the Centre for Vaccine Preventable Diseases at the University of Toronto’s Dalla Lana School of Public Health, told CBC News Network.
It’s similar to vaccines already on the market, such as the hepatitis B vaccine.
Novavax makes the protein by putting the genetic sequence for the protein into a virus that infects insect cells, causing them to make large quantities of protein. The protein has some small genetic modifications compared with the one found on the real virus to help it maintain a rigid shape and make it easier for the body to bind to and recognize.
Protein subunit vaccines don’t elicit as strong an immune response as whole virus vaccines, so they often include an adjuvant. Novavax uses a proprietary adjuvant called Matrix-M, which is based on a type of compound found in many plants called a saponin. The company says it boosts the body’s immune response and generates a bigger immune response with a lower dose.
Where it’s at: Novavax reports in a study preprint (not yet peer-reviewed) that in Phase 1 clinical trials, its protein and adjuvant stimulate high levels of neutralizing antibodies — higher than those in people who have had a natural infection — with few side effects. It’s currently running a combined Phase 1 and 2 trial.
Headquarters: New York, N.Y., U.S./Mainz, Germany
Doses reserved: At least 20 million
Phase of development: Phase 2/3 clinical trial started in July
How it works: Pfizer and BioNTech’s mRNA vaccine is quite similar to Moderna’s. It’s an mRNA sequence for a stabilized spike protein. Like Moderna’s vaccine, it’s delivered in a liquid nanoparticle container.
Where it’s at: Pfizer and BioNTech tested two different mRNA sequences for Phase 1. It reported in a study posted online that has not yet been peer-reviewed that both vaccines generated higher levels of neutralizing antibodies than found in the blood of someone who had had a natural COVID-19 infection. However, the spike protein sequence generated fewer side effects, especially in older adults, so that’s the focus of a combined Phase 2 and 3 trial.