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

Canada has signed deals with severalteamsof vaccine developersto reserve millions of doses of COVID-19 vaccines, including ones from Pfizer-BioNTech,Moderna,AstraZenecaand Janssen (Johnson & Johnson) thathavenow been approved in Canada under interim orders.

Government officials say it's part ofan effort to make sure Canadiansare at the front of the line when it comes to vaccine distribution.

Ottawa announced agreementswith ModernaandPfizer-BioNTechon Aug. 5, 2020;with NovavaxandJanssen, a subsidiary of Johnson & Johnson, on Aug. 31; with Sanofi/GSKon 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 receive20 million to 76 million doses of each vaccine that successfully makes it through clinical trials and be approved by Health Canada.

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

On Dec. 9, 2020,Pfizer-BioNTech's vaccine was approved in Canada under an interim order, a week after it wasapproved for emergency use in the U.K. Health Canada approved Moderna's vaccine under an interim order on Dec. 23, 2020,and approved AstraZeneca's vaccine under an interim order on Feb. 26, 2021, nearly two months after approval in the U.K. and a month after approval inthe European Union. Janssen'svaccine was approved in Canada under an interim order on March 5, 2021.

Novavaxhasreleasedpromisingresults from Phase 3 clinical trials,a key step to determine a vaccine'seffectiveness in preventing COVID-19 andsubmitted applications to Health Canada for approval.

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

Here's a closer look at the sevencandidates.

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: Approved for use in Canada under an interim order on Feb. 26, 2021

How it works:This vaccineis 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 coronavirus gene. The genecontains instructions for making a coronavirus proteinso 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, 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 thanDNA alone and helps get the coronavirus geneinto 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:The vaccine was approved in Canada under an interim order on Feb. 26, 2021. It had beenapproved for emergency use in the U.K.on Dec. 30, 2020 and in the EU on Jan. 29, 2021.However, Canada hadsaidit neededmore data. AstraZeneca and the University of Oxfordhad announced promising preliminary results of their Phase 3 clinical trialson Nov. 23.Results showedthe 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. That was due to a dosing error, leading to questions about the results and prompting the company to say it would run an additional global trial. Phase 3 trials of the vaccine started in August in the United States, following the start ofPhase 2/3 trials in the United Kingdom,Brazil and South Africa. While the trials were paused twicedue to illnesses among volunteers, the company says noserious 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 vaccinate38million)

Phase of development: Approved for use in Canada under an interim order on March 5, 2021

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. Another difference is it's beentested as a single-shot. Most other vaccines require two shots to be effective.

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

Where it's at: Health Canada approved the vaccine under an interim order on March 5, 2021.On Jan. 29, the company had announcedPhase 3 clinical trials showing the single-shotwas 66 per cent effective on average and 85 per cent effective against serious symptoms 28 days after vaccination. The overall effectiveness was as high as 72 per cent in the U.S., but only 57 per cent in South Africa, suggesting it is less effective against a new variant spreading there.The company ransingle-shot and two-shot clinical trials simultaneously. It had reported in July that its vaccine protected monkeys against the coronavirus after a single shot.

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Medicago

Headquarters:Quebec City, Que.

Type:Virus-like particle (VLP)

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

Phase of development: Phase 2/3 trial started in November

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.

The vaccine is being tested with an adjuvant made by GSK to boost the immune response.

Where it's at:The company startedPhase 2/3 clinical trials in Novemberafter announcing promising results from Phase 1 clinical trials that started in July. As of Oct. 23, the federal government had committed$428 million to complete clinical trials andestablish 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:40million (enough to vaccinate 20 million people)

Phase of development:In use in Canada after approval underan interim order on Dec. 23

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 lipidnanoparticle(LNP) 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 haveever been approved for widespread human use.

Where it's at:Canada approved Moderna's vaccine under an interim order on Dec. 23, 2020, and began vaccinations in January.In total, it has purchased40 million doses, but did notexercise the option to buy 16 million more. The company had announced on Nov. 16 that preliminary results of its Phase 3 clinical trial showthe vaccine is 94.5 per cent effective. After logging enough additional infections to end the trial, it announced on Nov. 30that it had confirmed an effectiveness of 94 per cent. The trial, which began inthe U.S. in July, enrolled30,000 adult volunteers, including "many" that are elderly or high-risk. Moderna said on Jan. 25 thatits vaccine appears effective against new coronavirus variants that first appeared in the U.K. and South Africa, but is less effective against the South African variant.

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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 3 clinical trials started in December in the U.K. and U.S.

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 withthe 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:Novavaxbegan Phase 3 clinical trials in December. On Jan. 29, it said preliminary results from the U.K. on a small number of people suggested that the vaccine was 96 per cent effective against earlier strains of coronavirus and 86 per cent effective against a new variantcirculating in the U.K. It is less effective against a new variantcirculating in South Africa. On Jan. 31, the company submitted an application for Health Canada approval, and on Feb. 2, Prime Minister Justin Trudeau also announced that Canada had signed a deal to produce the vaccine in Canada starting later in the year.

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), withthe governmentnegotiating for optionstoreservemore

Phase of development:In use in Canada after approval under an interim order on Dec. 9

How it works: Pfizer-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:Vaccinations are underway after the Pfizer-BioNTech vaccine wasapproved in Canada under an interim order on Dec. 9. 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. There were just eight infectionsamong volunteers who received the vaccine. The results were published in a peer-reviewed journal on Dec. 10. Studies so far suggest the vaccine is effective against some mutations found in new coronavirus variants in the U.K. and South Africa, but more research is needed on other mutations.

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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, 2020, but is restarting in February 2021

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 GSKand 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 thestart of a Phase 1/2 clinical trial on Sept. 3 involving 440 healthy adults at 11 sites across the U.S. However, on Dec. 11, the company said the vaccine would be delayed until late 2021 due to "insufficient" immune response in people over 60. That was partly due to them receiving a lower dose than intended. The company is planning to start a new early-stage trial in February. Sanofi says some research, development and clinical manufacturing of the vaccine will take place in Toronto.