Here's what needs to happen before we can all get vaccinated for COVID-19
Potential vaccine must pass animal tests, 3 levels of clinical trials
COVID-19 has upended our lives, and we've all heard that there will be no return to "full normal" until there is a vaccine for SARS-CoV-2, the coronavirus that has caused the pandemic. But how long will that take? What steps need to happen along the way? And where are we now? Here's a closer look.
How long will it take to develop a vaccine against the coronavirus?
When the World Health Organization first named the disease in February, it said the first vaccine wouldn't be available for 18 months. Since then, U.S. experts have said it would likely take 12 to 18 months while the European Medicines Agency has said a vaccine could be approved in about a year in an "optimistic" scenario.
That's much faster than the five to 10 years it normally takes to develop a vaccine.
WATCH | The race to develop a COVID-19 vaccine:
How is vaccine development going for COVID-19?
The good news: it's going much faster than normal.
The first human vaccine trials began in March, just two months after the virus and COVID-19, the disease caused by the virus, were identified. With the SARS epidemic in 2003, it took 20 months for a vaccine to get to the stage where it was ready for human testing —although the vaccine was never developed, as the epidemic was over by then.
As of May 15, the World Health Organization reported that there were 110 candidate vaccines in preclinical evaluation around the world, and eight in human Phase 1 and Phase 2 trials. A Phase 1 trial has been approved by Health Canada to take place in Halifax.
How do scientists come up with vaccine candidates?
Vaccines work by introducing your immune system to a germ or a piece of a germ so it will recognize it and learn to fight it off. Strategies for targeting the new coronavirus include using:
- A weakened but "live" virus.
- A dead or inactivated virus.
- A recognizable component or piece of the virus such as a protein or sugar.
- Genetically engineered RNA or DNA — this is a new approach being tried for this coronavirus. In most cases, it targets genetic material with instructions for making the S-protein, which forms the crown-like spikes on the surface that gives coronavirus its name and bind to human cells to infect them.
Initial lab tests in petri dishes and test tubes show whether a particular approach has the potential to be effective as a vaccine.
What is preclinical evaluation?
Tests that don't involve humans are called "preclinical."
Once a vaccine candidate shows promise in the lab, tests are run in animals to show it is safe and effective.
The World Health Organization says those tests are used to help:
- Ensure none of the ingredients are toxic or react with trace impurities to produce toxic effects, and they don't interact negatively with other vaccines given at the same time.
- Determine the dose needed to induce an immune response.
Animal testing usually takes three to six months, according to the U.S.-based Mayo Clinic.
However, animals don't necessarily react the same way as humans to either an infectious agent such as a virus or to a vaccine. That's why vaccines that make it through preclinical evaluation don't necessarily go on to become vaccines.
What is a Phase 1 clinical trial?
Once a vaccine has been shown to be safe and effective in animals, the first tests on human volunteers — Phase 1 clinical trials — are run primarily to test for safety.
They typically involve 10 to 100 healthy adults, even if they aren't the target age group. According to the U.S. Centers for Disease Control, they're intended to find out:
- Is the vaccine safe?
- Does it work?
- Are there any serious side effects?
- How is the size of the dose related to the side effects?
The Phase 1 coronavirus vaccine trial being run in Halifax began with "very healthy volunteers" between the ages of 18 and 55. Volunteers older than 65 will be added if early trials show the vaccine is safe.
Volunteers are typically monitored for six to 12 months, but Phase 2 trials can begin before Phase 1 is complete if the vaccine seems safe. That's what is happening with some coronavirus vaccine trials, which are starting Phase 2 after only a few weeks of successful Phase 1 trials.
What is a Phase 2 clinical trial?
The larger Phase 2 trial involves several hundred healthy volunteers, this time from the group targeted for the vaccine. The key questions at this stage are:
- What are the most common short-term side effects?
- How are the volunteers' immune systems responding?
- What is the optimal dose for the vaccine and when should it be administered?
Phase 2 trials for the vaccine being tested in Canada will take six months, said Scott Halperin, director of the Canadian Centre for Vaccinology at Dalhousie University in Halifax, which is running the first clinical trials in Canada.
What is a Phase 3 clinical trial?
This phase usually involves even more volunteers — up to 30,000 people — from the population susceptible to the disease, which includes all ages in the case of COVID-19. Key questions at this point are:
- Is the vaccine effective in protecting against the disease in the type of patient likely to use it?
- Is the dose correct?
- Is the vaccine safe?
- What are the most common side effects?
- Are there any side effects or reasons why certain people should not be given the vaccine?
Phase 3 can last years.
After that, how does a vaccine get approval?
In Canada, manufacturers apply for approval by filing a New Drug Submission with Health Canada's Biologic and Radiopharmaceutical Drugs Directorate. It needs to include:
- Scientific and clinical evidence that the vaccine is safe, effective and of high quality.
- Information about the manufacturing facility, method of production and quality controls for making the vaccine.
Health Canada evaluates the data to verify that:
- The vaccine is safe.
- It is effective.
- The benefits outweigh the risks.
It also reviews procedures for safety monitoring once the vaccine is in use.
If the vaccine meets requirements, it is issued a Drug Identification Number (DIN) and a Notice of Compliance (NOC) and authorized for sale in Canada.
However, even then experts warn there can be challenges with manufacturing and distributing enough for the entire population in the case of a global pandemic like COVID-19.
Can a vaccine that isn't approved be distributed in Canada in emergencies?
Yes, during public health emergencies such as pandemics, Health Canada can issue special authorizations for vaccines that aren't approved in Canada. For example, in 2009, Health Canada used an interim order to approve an H1N1 vaccine based on clinical trial data in Europe, even though clinical trials had only just started that same week in Canada.
Once a vaccine is approved, is the research over?
No. Vaccines need to be monitored after use, partly because some side effects happen so rarely that they're only detectable in a very large population, bigger than any clinical trial.
Health-care providers are asked to report adverse reactions to their local health units, and manufacturers must report all serious adverse reactions both in Canada, and internationally, to Health Canada within 15 days. The public can also voluntarily report adverse reactions to Health Canada.
Many vaccines also have formal ongoing "Phase 4" studies that continue after the vaccine is approved and in use.
In response to safety reports or other new information, Health Canada can also order manufacturers to assess their product's risks and benefits or perform further tests and studies on its safety and effectiveness at any time.
Corrections
- A previous version of this story incorrectly said the SARS epidemic took place in 2009. In fact, it took place in 2003.May 25, 2020 6:51 AM ET
