Health

A closer look at the vaccines Canada is betting on to stem the spread of COVID-19

The federal government has announced that it has signed deals with several groups of vaccine developers to reserve millions of doses of COVID-19 vaccines under development. The candidate vaccines represent a variety of different technologies with different pros and cons. Here’s a closer look.

Ottawa has signed deals for millions of doses of vaccines from several groups of developers

The first patient enrolled in Pfizer's COVID-19 coronavirus vaccine clinical trial at the University of Maryland School of Medicine in Baltimore receives an injection in May. Pfizer's vaccine candidate is one of five that Canada has announced deals to reserve. (University of Maryland School of Medicine/The Associated Press)

Canada has announced that it has signed deals with several teams of vaccine developers 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.

The federal government announced agreements with Moderna and Pfizer/BioNTech on Aug. 5; with Novavax and Janssen, a subsidiary of Johnson & Johnson, on Aug. 31; with Sanofi/GSK on Sept. 22; with AstraZeneca, which is manufacturing a vaccine developed at the University of Oxford, on Sept. 25; and with Medicago on Oct. 23.

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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The seven vaccines are among more than 150 candidates under development around the world.

So far, only AstraZeneca's and Pfizer's have completed their Phase 3 clinical trials, a key step to determine a vaccine's effectiveness in preventing COVID-19. And the full data has not yet been released or peer reviewed. Another, Moderna's, has shown promising preliminary results in Phase 3 clinical trials. None have yet received government approval, although Canada is reviewing the preliminary data from some of the trials.

In total, the federal government has committed $1 billion and most of that money will not be refunded even if the vaccines never get approved.

"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 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 seven candidates.

AstraZeneca/Oxford University

Headquarters: London, U.K.

Type: Non-replicating viral vector

Doses reserved: 20 million (enough to vaccinate at least 10 million people)

Phase of development: Phase 3 trial started in August, overlapping with Phase 2/3 trials that started earlier

How it works: This vaccine 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 the chimpanzee version of 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.

Viral vector vaccines mimic viral infection more closely than some other kinds of vaccines. One disadvantage of viral vectors is that if a person has immunity toward a particular vector, the vaccine is not as effective. In this case, people are unlikely to have been exposed to a chimpanzee adenovirus.

Where it's at: On Nov. 23, AstraZeneca and the University of Oxford announced promising preliminary results of their Phase 3 clinical trials. Results showed the vaccine was up to 90 per cent effective at preventing COVID-19. It was more effective when the first dose was a half dose and a full dose was given a month later. Phase 3 trials of the vaccine started in August in the United States, following the start of Phase 2/3 trials in the United Kingdom, Brazil and South Africa. While the trials were paused twice due to illnesses among volunteers, the company says no serious safety events related to the vaccine have been confirmed

Janssen Pharmaceutical Companies (Johnson & Johnson)

Headquarters: Raritan, N.J., U.S.

Type: Non-replicating viral vector

Doses reserved: Up to 38 million (enough to vaccinate 19 million or 38 million people)

Phase of development: Phase 3 trial started in September

How it works: This vaccine, made by a Johnson & Johnson subsidiary, is similar to the one from AstraZeneca and the University of Oxford except that it uses a slightly different adenovirus.

Its advantages are similar, but 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.

While this is a relatively new technology, a replicating viral vector vaccine, which is similar, has been approved for protection against Ebola, and there are at least a dozen viral vector vaccines in use for diseases in livestock.

Where it's at: The company announced on Sept. 23 it had launched a Phase 3 clinical trial that will include 60,000 people in Argentina, Brazil, Chile, Colombia, Mexico, Peru, South Africa and the U.S. The company is running single-shot and two-shot clinical trials simultaneously. It had reported in July that its vaccine protected monkeys against the coronavirus after a single shot. 

WATCH | Fast-tracking a COVID-19 vaccine is not without controversy:

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Medicago

Headquarters: Quebec City, Que.

Type: Virus-like particle (VLP)

Doses reserved: 76 million (enough to vaccinate 38 million people)

Phase of development: Phase 1 trial started in June

How it works: Medicago's vaccine is more traditional than the non-replicating viral vector vaccines. Like many vaccines already on the market, it's made up of a protein from a virus, the spike-protein from SARS-CoV-2.

It's slightly more sophisticated than traditional protein-based vaccines, as multiple spike proteins are assembled into a virus-like particle, or VLP. The company says that makes it look more like a virus to the immune system than disorganized protein molecules would.

The particles are made by inserting the spike protein gene into plants — tobacco relatives called Nicotiana. They're extracted by crushing the leaves.

Where it's at: The company started Phase 1 clinical trials in July. As of Oct. 23, the federal government had committed $428 million to complete clinical trials and establish a large-scale vaccine and antibody production facility in Canada. Currently, its main vaccine production facility is in the U.S. 

Moderna

Headquarters: Cambridge, Mass., U.S.

Type: mRNA

Doses reserved: Up to 56 million (firm commitment on 20 million, enough to vaccinate 10 million people; with an option for 36 million more, enough to vaccinate another 18 million more)

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 lipid 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 announced on Nov. 16 that preliminary results of its Phase 3 clinical trial show the vaccine is 94.5 per cent effective so far. However, the trial is ongoing and Moderna acknowledged the protection rate might change as more COVID-19 infections are detected and added to the calculations. The trial, which began in the U.S. in July, has enrolled 30,000 adult volunteers, including "many" that are elderly or high-risk. 

WATCH | A look at Moderna's promising results:

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Novavax

Headquarters: Gaithersburg, Md., U.S.

Vaccine type: Protein subunit

Doses reserved: 76 million (enough to vaccinate 38 million people)

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, and announced on Aug. 24 that it had begun the Phase 2 portion of the trial.

Vials used by pharmacists to prepare syringes used in a first-stage safety study clinical trial of a potential COVID-19 vaccine are seen on March 16, 2020. The world's biggest COVID-19 vaccine test got underway Monday, July 27 with the first of 30,000 planned volunteers. (Ted S. Warren/The Associated Press)

Pfizer/BioNTech

Headquarters: New York, N.Y., U.S./Mainz, Germany

Type: mRNA

Doses reserved: At least 20 million (enough to vaccinate 10 million people), with the government negotiating for options to reserve more

Phase of development: Phase 3 clinical trial started July 27

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 lipid nanoparticle container.

Where it's at: Pfizer announced on Nov. 18 that it had completed its Phase 3 clinical trial, and the updated preliminary results show the vaccine is 95 per cent effective. That's based on 170 infections in a trial of more than 43,000 participants in six countries. Just eight infections were among volunteers who received the vaccine. The full data has not yet been publicly released, peer reviewed or published. Pfizer says it will seek emergency use authorization in the U.S.

WATCH | An expert looks at Pfizer's clinical trial results:

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Sanofi/GSK

Headquarters: Paris, France/London, UK

Type: Protein subunit

Doses reserved: Up to 72 million (enough to vaccinate up to 36 million people)

Phase of development: Phase 1/2 trial started on Sept. 3

How it works: This is very similar to Novavax's vaccine — it's made up of the SARS-Cov-2 spike protein with a proprietary adjuvant to boost the body's immune response. In this case, the adjuvant is made by GSK and is also being tested with a number of other vaccines, including the one being developed by Quebec City-based Medicago. Like Novavax, Sanofi is making the protein by putting the gene for it into a virus that infects insect cells. It's the same system used by Sanofi to make a flu vaccine that has government approval for widespread use. This is one of two COVID-19 vaccines Sanofi is working on. The other is an mRNA vaccine in collaboration with Translate Bio.

Where it's at: Sanofi and GSK announced the start of a Phase 1/2 clinical trial on Sept. 3 involving 440 healthy adults at 11 sites across the U.S. They expect to get results in early December 2020. Sanofi says some research, development and clinical manufacturing of the vaccine will take place in Toronto.

About the Author

Emily Chung

Science and Technology Writer

Emily Chung covers science and technology for CBC News. She has previously worked as a digital journalist for CBC Ottawa and as an occasional producer at CBC's Quirks & Quarks. She has a PhD in chemistry.

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