As the global pandemic continues, scientists around the world are working at breakneck speed in an effort to develop safe and effective vaccine candidates against COVID-19. Given the unprecedented scale of the response, the general timeline researchers across the planet are aiming for is to have a viable vaccine ready and available for distribution within a year to a year and a half. Typically, vaccine development takes anywhere from 5 to 15 years.
Here in Canada, researchers at the NRC are mobilizing efforts by leveraging their considerable expertise and innovative technology platforms to accelerate development as much as possible.
The scope of the challenge
When presented with a virus, the human immune system produces antibodies to fight off the infection. Unfortunately, sometimes the immune system can't react quickly enough. Broadly speaking, a vaccine provides the immune system with an advance warning, so that it can prepare antibodies before possible infection occurs.
"Vaccine development generally involves targeting the surface protein of the virus in question, and finding a way to safely deliver it to the human body in such a way that the immune system will recognize the virus and develop antibodies against it," says Lakshmi Krishnan, Acting Vice President of the NRC's Life Sciences division. "From a general perspective, many different types of approaches need to be tested and validated to ensure the body can produce a safe and effective vaccine-induced immunity against a specific component of the virus, which can then protect against real infection in the future. Once viable candidates are identified, we need to be able to reliably manufacture large quantities of these vaccines, usually using living cells, and test them in a number of different and highly precise ways in a laboratory setting to ensure their safety and efficacy. This is where the Human Health Therapeutics Research Centre excels, in terms of both expertise and facilities, and its ability to accelerate vaccine development."
Once a potential vaccine candidate is proven safe and effective in the laboratory, it would then move to a rigorous process of testing in humans, called clinical trials, which are regulated by Health Canada. The first phase involves testing for safety in a small number of healthy volunteers to ensure there are no unintended side effects, before moving to a second phase focussed on demonstrating vaccine-specific immunity in a larger population. Finally, a third phase would confirm the efficacy of the vaccine and longevity of the response in a larger population of individuals with the infection. All phases of clinical trials are done with rigorous monitoring by doctors, and the protocols and results are carefully reviewed by Health Canada to ensure that, along each step of the way, the health and wellness of participants is ensured. Of course, even after all this is accomplished, before a vaccine can be distributed there needs to be a value chain in place, made up of highly specialized equipment, personnel, and resources in a controlled environment, to allow the vaccine to be reliably manufactured at a high quality on a massive scale. This is referred to as Good Manufacturing Practice (GMP), and is again a regulated process approved by Health Canada for each product. The NRC is upgrading the pilot manufacturing plant at its Royalmount facility in Montreal for GMP compliance, so it will be available to produce candidate vaccines for both clinical trials and future use in humans.
To get a sense of the scope of the challenge, it may be helpful to review a few basics when it comes to what vaccines are, and how they work.
To treat or prevent
If you've ever been to a doctor you may remember that antibiotics can potentially be used against bacterial infections, but are of no help against viral infections. Once a patient has been infected with a virus, it's a race against time – either the patient's immune system develops antibodies quickly enough to fight off the infection, or it doesn't. In order to provide treatment, doctors can attempt a broad array of generalized approaches to tackle the symptoms and buy some more time for the immune system to do its work.
To create a vaccine, on the other hand, scientists can't just target general symptoms of the disease. Instead, they have to go squarely after the specific genetic make-up of the virus that causes the disease in the first place, to try and prevent it from being able to take hold before a person gets sick.
Collaborative innovation and leveraging key Canadian expertise
The NRC is working with trusted partners as part of a collective effort to help find solutions to the COVID-19 outbreak.
On February 2, 2021 the Government of Canada announced it signed a memorandum of understanding with Novavax to pursue options to produce its COVID-19 vaccine at the NRC's Biologics Manufacturing Centre once both the vaccine candidate and the facility receive the required Health Canada approvals. The Novavax vaccine candidate, NVX-CoV2373, is a protein subunit vaccine.
The NRC will now explore the use of its proprietary HEK293SF-3F6 mammalian cells to develop a robust and efficient process to scale up production of the vaccine antigen for future pre-clinical and clinical studies.
Dr. Lakshmi Krishnan says: "Until there is an effective vaccine that is widely available for Canadians, COVID-19 will continue to disrupt all aspects of our society and economy. With Canadian expertise and facilities, the NRC is working hard to collaborate nationally and internationally to innovate, advance science, and support biomanufacturing as we find solutions for protecting and treating Canadians affected by the pandemic."
Virus vs. disease
Among scientists, the current coronavirus is referred to as SARS-CoV-2 – which stands for severe acute respiratory syndrome coronavirus 2 (the "2" distinguishes it from the disease most of us know simply as "SARS").
The disease caused by SARS-CoV-2 is COVID-19 – meaning 'coronavirus disease 2019'.
What are antigens?
An antigen is anything that stimulates a response in the immune system. When a person gets a virus, their immune system tries to produce antibodies to fight off the infection. But sometimes the immune system can't react quickly enough. A vaccine provides the immune system with an advance warning, so that it can prepare antibodies before possible infection occurs.
In general terms, a vaccine needs to reproduce the surface protein or DNA of the virus in an inactivated form – this is the antigen. Antigens are developed in the laboratory and produced in living cells whose properties are known to the researchers. For example, the NRC has developed a proprietary HEK293SF-3F6 cell line that can be used to develop biologic medicines such as vaccines.