The race for a COVID-19 vaccine

A lthough Canada has done relatively well in comparison to numerous other countries throughout the world in controlling the number of cases and deaths from SARS-CoV-2, the bad news is that, sadly, the virus is still with us and the pandemic is not over. We are very fortunate in Canada to have not only excellent government leadership and support in managing this pandemic, but also the most well-developed public health care system in the world! Yes! In a January 2020 survey conducted by the US News and World Report , Canada was ranked first in having the best public health care system in the world, followed by Denmark, Sweden, Norway, and Germany. ¹ We should definitely be very proud of our health care system and the work of Health Canada and the Public Health Agency of Canada (PHAC), both of which are part of Canada’s Health Portfolio headed by the federal minister of health.

Over the past several months we have seen a flattening of the epidemic curve across Canada, which has permitted most provinces to enter “Phase 3” of reopening and enabled dental offices to offer non-essential oral care services again, of course with very strict guidelines from both Health Canada as well as our professional and regulatory organizations. This re-entry has been challenging for many and very disheartening as we have begun to see our infection numbers climb once again in recent weeks, reminding us we are not yet “back to normal,” nor will we be until there is a vaccine. The race now seems to be on throughout the world to develop a vaccine and, in most cases, at “warp speed.” The first human vaccine trial began in March 2020. Normally, it takes between 5 and 10 years to develop a vaccine, yet there are already predictions by many researchers and scientists that there may be one available by the end of this year or certainly early next year! The speed at which these vaccines are being developed is unprecedented and, in some cases, has led to uncertainty and concern over the rigour with which the safety and efficacy of these vaccines will be established.

Salme E Lavigne

As health care professionals, we may be asked questions by our clients about how these vaccines are made, what the testing process involves, if they will be safe, and why it’s taking so long. Just a quick recall of microbiology 101: a vaccine is made from either a dead (inactivated) organism or a component of that organism, or from a live but attenuated (weakened) microbe. In both cases, your immune system will recognize it as something foreign and begin to prime memory T-cells, which activate B-cells to produce antibodies against it. Once developed, those antibodies are stored as immunoglobulins within the immune system and, if the individual is exposed to that particular microbe, the antibodies will be activated and will fight off the particular microbe, preventing the disease from occurring.

There are currently several strategies being used to develop a vaccine for the novel coronavirus in addition to the ones already mentioned. For example, some companies are genetically engineering either the DNA or the RNA of the coronavirus to stimulate the creation of antibodies. In May 2020, the World Health Organization reported that there were 110 potential vaccines being clinically evaluated throughout the world. One of those under evaluation was approved by Health Canada for a Phase 1 trial in Halifax. ² Currently there are 3 vaccine trials approved in Canada, with the Halifax trial now in Phase 3.

You may ask what does that mean? The process for getting approval to commence the development of a vaccine begins first with research; then with a preclinical evaluation not involving humans; then 3 separate phases of human clinical trials, which are all randomized controlled trials (RCTs) that have both a test group and a control group.

Research

In this initial phase, the manufacturer must first map the genome of the virus and then test different approaches for vaccine development. In the case of COVID-19, researchers had a head start as the genome had already been sequenced and they were able to follow similar approaches to previous research on other vaccines.

Preclinical phase

This phase is conducted in the lab and involves testing for safety and efficacy on animals. Typically, this preclinical phase can take up to 6 months. If results show promise and pass the safety and efficacy tests, the research then moves into human clinical trials to see if the vaccine is safe and effective to use on humans.

Phase 1 clinical trials

Phase 1 involves testing the vaccine on 1 to 100 human volunteers for both safety and effectiveness for 6 to 12 months. Side effects and their seriousness are assessed. The trials usually recruit healthy volunteers rather than people who may be health compromised just in case there are serious side effects. This phase is very important as animals do not necessarily respond in the same way that humans do. Often there may be no efficacy found in this first phase of human trials, in which case the vaccine study is ended. However, if the drug shows some efficacy and most importantly seems safe, Phase 2 trials can begin earlier.

Phase 2 clinical trials

In this phase, 50 to 500 healthy volunteers are recruited. This phase checks for safety and measures the immune response. At this stage, there is also the determination of what the best dosage would be and whether more than 1 dose is required to achieve the desired level of immunity. Typically, these trials in Canada take 6 months.

Phase 3 clinical trials

Phase 3 is the final “real world” check across a much broader population to measure both safety and efficacy. Between 300 and 30,000 volunteers are recruited and, in the case of COVID-19, volunteers from more susceptible high-risk population groups are included to see if the vaccine can prevent infection and even severe infection within the community as a whole. This phase is lengthy, potentially lasting years. However, if both safety and efficacy are found to be high, then an early release of the vaccine could occur in cases such as pandemics. It is well known that efficacy of any vaccine is never 100%. In fact, the annual flu vaccine efficacy ranges between 40% and 60%. Both the US Food and Drug Administration and Health Canada typically require at least 50% efficacy before approving a vaccine. Final vaccine approval is granted by Health Canada after rigorous scrutiny, and the vaccine continues to be monitored by Health Canada for side effects and safety even after initial approval and distribution.

The biggest challenge yet to come in the current pandemic will be the management of the supply and distribution of the vaccine to the population at large. Questions may arise such as when will the vaccine be available and who will get the vaccine first? Dr. Theresa Tam, chief public health officer of Canada, recently indicated that PHAC is working on a priority list, which will soon be released to the public. She also indicated that “widespread vaccine uptake is Canada’s best shot at regaining any semblance of pre-pandemic normalcy.” ³ The good news is that living in the country with the best public health care system in the world offers advantages! A plan is already in place for procuring the necessary supplies, such as alcohol swabs, bandages, gauze, manufacturing and packaging materials, as well as enough vaccines for the entire population of Canada at no cost to individuals. The federal government has already signed contracts with 4 of the leading vaccine pharmaceutical companies to secure a minimum of 88 million doses of COVID-19 vaccines—enough to provide 2 doses for every Canadian. They are currently working on securing contracts from 2 more companies to ensure that, regardless of who releases the vaccine first, Canada will be among the first in line.

To address public concerns about the safety and efficacy of these vaccines given the speed at which they are being developed, the chief executive officers of 9 vaccine manufacturing companies have signed a pledge to “uphold the integrity of the scientific process.” ⁴ These companies include all of those with which Health Canada has contracts. We will be well protected! In the meantime, have patience, stay safe, wash your hands, wear a mask, keep physically distant, and continue to avoid large crowds.

The Chinese use two brush strokes to write the word “crisis.” One brush stroke stands for danger; the other for opportunity. In a crisis, beware of the danger but recognize the opportunity!

—John F Kennedy