COVID-19 Vaccines: Part II – Canada

What about Canada? There will be a third blog dealing with the world as a whole.

249,000 doses. They are promised to arrive next week. Final approval from health Canada of that Pfizer vaccine is expected at the end of this week. One source of delay is a step I had not known about or anticipated. Pfizer has to approve the 14 nodes set up for initial distribution to ensure that their vaccine can be stored, prepared and offered without risk to either the vaccine or patients. Evidently that will only take a day or two.

However, the information changes not only daily but hourly – until yesterday morning’s announcement by Prime Minister Trudeau, I had been led to believe that the vaccine would not arrive until January, already a revision to my previous information of arrival in March. I have proven not to be a reliable source on timing. Thus, some of the content may be outdated by the time you read this blog. Nevertheless, it is helpful to periodically collect what one has learned.

Canada has passed the 400,000 COVID-19 case mark and almost half those cases have been reported within the last three weeks. Over the last two days, Ontario reported 1925 and 1924 cases in that order and 26 deaths as the latest count per day. The federal government has signed contracts with five Vaccine Logistics Service Providers to deliver 358 million doses over the next two years. By January, Canada is expected to receive three million doses.

With one Canadian addition, the vaccines will be obtained from the same developers and manufacturers used in the U.S. But why 358 million doses when we need only 70 million at most for every man, woman and child to receive a COVID-19 vaccine? And why two years? Why not six months as in the U.S.? Well, it may be not much more than six months. The government does not want to raise expectations and then disappoint if things go awry in any way.

Agreements have been signed with Moderna and Pfizer/BioNTech (5 August), Johnson and Johnson via their subsidiaries, Novavax and Janssen (31 August), Sanofi/GSK (22 September), AstraZeneka (25 September) and Medicago (23 October). In light of the recent rapid increase in occurrences of the disease, federal officials scrambled to double Canada’s vaccine order with Moderna to 40 million doses. But there are serious challenges in distribution given that the initial vaccines available have to be kept at -80 degrees. That means that distributing this vaccine creates costly and complex logistical challenges and make it almost impossible to distribute the vaccine to northern indigenous communities that are in such great need.

The two vaccines first off the starting line are based on priming the immune system’s defences against the viral “spike protein” rather than a weakened version of the disease itself, the traditional method for producing vaccines. Though advances in the use of this method largely came from years of research led by Barney Graham, Deputy Director at the U.S. National Institutes of Health facilities in Maryland, the original idea and initial research for the development of the use of the spike protein on the mRNA, that is, the messenger RNA, came from two other American researchers at the University of Pennsylvania who will undoubtedly win a joint Nobel Prize in Medicine, Katalin Kariko and Drew Weissman.

The transient genetic material takes the instructions inscribed in DNA and delivers a genetic code rather than the vaccine itself to the protein-making parts of the cell so that the cells themselves become protein immune factories for preventing the spike protein from adhering to the cell. In effect, humans are turned into immune protein production factories. Thus, we can encode fragments of a virus to teach the immune system to defend against pathogens. Even more significantly, this methodology could also create whole proteins that are missing or damaged in people with devastating genetic diseases, such as cystic fibrosis.

One of the major challenges of the Health Institutes research was the instability of the mRNA as well as figuring how the spike protein adhered to the cell. Research revealed that the spike protein folded like origami, from a thumbtack-like shape before fusing with cells, to a rodlike shape afterward. One needed only to disrupt this transformation by enabling the immune system to recognize and then attack the thumbtack spike, a breakthrough accomplished by the painstaking work of Nianshuang Wang in the McLellan Lab at the University of Texas at Austin. He and the others mentioned are part of the immense army of scientists at diverse research centres who facilitated the development of the vaccines. It is noteworthy that a high proportion of the scientists were immigrants o children of immigrants.

In summary, the Pfizer and Moderna vaccines work as follows:

  1. RNA vaccines contain a strip of genetic material within a lipid bubble.
  2. Inside the cell, ribosomes read the mRNA instructions for the spike protein.
  3. The cell then begins to generate copies of the spike protein.
  4. Antigen-presenting cells (APCs) consume the viral proteins and pass viral peptides to T-helper cells.
  5. The immune system, presented with the peptide, learns to recognize the virus and releases cytotoxic T cells and B cells.
  6. Cytotoxic T-helper cells detect and eliminate virus-infected cells.
  7. Antibodies from B-cells block the virus from infecting healthy cells.

In contrast to Pfizer and Moderna, AstraZeneca stands out, not only for producing the least expensive vaccine at 20% of the cost of the others, as well as much cheaper storage and shipping costs, it has pledged to provide the vaccine on a not-for-profit basis for the “duration of the pandemic”, and in perpetuity to low- and middle-income countries.

The large number of doses ordered by Canada was intended as a risk-averse strategy to ensure that Canada had sufficient vaccine that worked, that is 8 doses per person with a contingency of an additional dose as an example of very deliberate insurance in case of missteps and unsuccessful vaccines. Canada has arranged for the highest number of doses in the world per Canadian citizen.

Though Canada is only offering guidelines to the provinces for distribution priorities, and the provinces will have the final say, Canada has a different recommended priority system than the United States which has made front-line health care workers its highest priority. In Canada, based on an independent advisory panel, residents in long-term care facilities (LCFs) and staff will be first in line for COVID-19 vaccines followed by the elderly (those over 80-years of age), especially those with pre-exiting conditions that make them more susceptible to very serious illness as a result of the disease. Neither the United States nor Canada has prioritized super-spreaders, the most effective method of countering the spread of the disease, but also the most difficult to identify and the most controversial group ethically to offer the vaccine. Both countries favoured making risk to the most vulnerable the highest priority.

According to Caroline Quach, an infectious disease specialist at the Sainte-Justine University Hospital Centre in Montreal who chairs the National Advisory Committee on Immunization, “Our aim is to protect the most vulnerable first. We have started with the elderly in long-term care facilities and their staff because that is where the highest burden of illness is.” In contrast, Britain, which has just received its first deliveries of the vaccine, has prioritized health care workers followed by residents and workers in long-term care facilities. “U.K. residents who are over 80, nursing home residents and frontline health care workers are among the first to receive the vaccine.”

In addition, Sanofi/GSK has a contract to provide 200 million doses to WHO on behalf of a consortium of countries (COVAX) that includes Canada, but Sanofi/GSK will not begin Phase III trials until the new year. The ACT Accelerator, a global collaboration parallel to America’s Operation Warp Speed, was created to accelerate the development, production, and equitable access to COVID-19 tests, treatments, and vaccines. COVAX is co-led by Gavi, the Coalition for Epidemic Preparedness Innovations (CEPI) and WHO. WHO plans include providing every country in the consortium with 20% of its needs before any country receives additional doses.  At the same time, WHO has supported building manufacturing capabilities and buying supply ahead of time so that 2 billion doses can be fairly distributed by the end of 2021. In the meantime, it has secured an estimated 700 million vaccine doses so far. More than 189 countries have signed up to COVAX, including wealthy economies that have joined to subsidize vaccine access. If Canada ends up with excess doses, as expected, the plan is to contribute this excess to COVAX.

Medicago, a Quebec-based pharmaceutical, is the only Canadian-based vaccine manufacturer, but it lags significantly behind its global rivals in the development of its vaccine. It has promising but preliminary results from its Phase I trials on 180 volunteers, including both those who received a placebo and those that received the vaccine. The federal government has contracted to buy 76 million doses of its vaccine and will also invest $173 million in Medicago for its vaccine research and development and for the construction of its Quebec City manufacturing facility.

Trial runs in Canada are underway this week. Approval is expected by the end of the week for the Pfizer vaccine, the same time as the U.S. Originally, it was believed that Canada was probably three months behind America in its ability to get the vaccines. That time delay was shortened to two weeks for delivery to the distribution nodes in each province and now the gap has been reduced to no gap at all. Moderna has assured Canada that it is not only not at the end of the line, but that it will receive vaccines quickly. Canada is set to receive six million doses of these two vaccines by the end of March, four million Pfizer doses and two million Moderna doses. (It is noteworthy that in 2016, Moderna researchers developed a nanoparticle to deliver messenger RNA to a special cell type that could take the code and turn it into a protein on its surface to provoke the immune system.) That means that three million Canadians will be vaccinated by the end of March. The production of vaccines will snowball from month to month as more producers come on line.

While the Canadian federal government is responsible for the procurement and approval of vaccines for use in Canada, the provinces are responsible for the overall immunization strategy. Politics has entered the picture in a significant way as provincial premiers lobby Ottawa for additional health funding, even though Ottawa has paid 80% of the costs for battling the pandemic thus far. There are also politics at the provincial level. The Province of Ontario has been accused of giving in to business pressures (particularly around public gathering spaces like restaurants, bars, gyms and places of worship) compared to the advice received from medical experts and its own public health agency. Further, the province has offloaded the responsibility for restrictions onto municipalities. All of this adds to the concerns re delays in getting the vaccine. There are also rumors that the province is planning to grant long-term care facility owners and operators immunity from liability for the more than 1,800 resident deaths during the first phase of the pandemic.

Municipalities, responsible for immunization at the local level are also making plans, including allocating and distributing allotted vaccine doses, working with medical practitioners, administering vaccines through clinics and other methods, and providing data to the Province to evaluate the success of the campaign. For example, the City of Toronto initiated a COVID-19 Immunization Task Force under Chief Matthew Pegg of the Toronto Fire Services to plan storage, distribution and organizing prioritization for the vaccines as they become available using the COVID-19 incident management system that the City has developed. This includes prioritizing targeted neighbourhoods experiencing higher numbers of COVID-19 cases, expanding testing sites, using buses for mobile testing units, extending testing hours and even providing transportation, intensifying community outreach and engagement and dealing with threats of unemployment or eviction for persons infected and the need for emergency assistance. 

One comment on “COVID-19 Vaccines: Part II – Canada

  1. Yoel Abells says:

    I am particularly disturbed that primary care has not been invited to the table to discuss the strategy for wide dissemination of the vaccine. The truth is that every year, and in particular this year, both the government and public health were way behind the eight ball in terms of flu vaccine distribution to our communities (truthfully, this is a recurring theme). Although we are the group that are best suited to provide the vaccines and certainly the group that patients feel they can trust most (as evidenced by many surveys) we are seldom considered in the planning discussions until the “boat has left the dock”. This year, many primary care providers thought outside the box and developed strategies to maximize flu vaccine distribution and uptake.

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