Quest for a vaccine: NRC researchers mobilize to advance technologies against COVID-19


- Montreal, Quebec

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 National Research Council of Canada (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.


Dr. Lakshmi Krishnan, Director General of the NRC's Human Health Therapeutics Research Centre.

"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, Director General of the NRC's Human Health Therapeutics Research Centre. "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

As of this writing, there are hundreds of potential treatments for COVID-19 being studied, and in some cases evaluated in human clinical trials, to treat those who have already been infected. But although there are over 100 vaccine candidates being evaluated in laboratories around the world to prevent the disease, so far fewer than 10 have been approved for testing in humans.

Quick fact – 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'.

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


CanSino Biologics is headquartered in Tianjin, but has strong ties to Canada, including a Canadian subsidiary based in Toronto.

The NRC is working with a number of trusted partners both in Canada and internationally, as part of a collective effort to help find solutions to the COVID-19 outbreak.

For example, a collaborative project to develop a pan-coronavirus vaccine candidate targeting COVID-19, SARS and MERS was recently announced with VBI Vaccines, which is headquartered in Massachusetts, with research operations in Ottawa. It is currently at the preclinical stage, with the aim of hopefully moving into human clinical trials sometime next year.

In addition, building on a technology platform that was previously developed in collaboration with the NRC, CanSino Biologics co-developed a vaccine candidate in partnership with the Beijing Institute of Biotechnology, which delivers a version of the spike protein associated with COVID-19 to the body in a safe form, thereby stimulating the immune system to create antibodies against it.

In March, the candidate vaccine was approved for Phase I human clinical trials in China, and in April received Chinese regulatory approval for Phase II trials. It was the first candidate vaccine in the world against COVID-19 to begin conducting Phase II clinical testing. The NRC is now working with CanSino to begin the process of evaluating the possibility of bringing this candidate vaccine to Canadian patients.

Quick fact – 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 HEK293 cell line that can be used to develop biologic medicines such as vaccines.

Building on a successful partnership

Although CanSino Biologics is headquartered in Tianjin, the company has strong ties to Canada, including a Canadian subsidiary based in Toronto. The relationship between the NRC and CanSino was first established in 2013. Most recently, the NRC's HEK293 cell line was licensed to CanSino and used in the development of a vaccine against the Ebola virus.

"Our collaboration brought together 2 technologies – CanSino developed an effective antigen for the virus, and the NRC's HEK293 cell line technology was used to produce the cells that contain the antigen," says Lakshmi Krishnan.

This time around, the same basic technology platform is being brought to bear on a different antigen – one that's aimed specifically at COVID-19 (namely, the "spike protein" that gives the coronavirus its name). Contingent on approval by Health Canada, the NRC will work with the Canadian Center for Vaccinology to enable Canadian clinical trials of CanSino's vaccine candidate, which is referred to as Ad5-nCoV. By starting the process of scaling up GMP biomanufacturing capacity in Canada, the NRC and its partners are ensuring Canadian production capacity will be available so the candidate vaccine can be brought to Canada in short order.


Dr. Xuefeng Yu, Chairman and CEO of CanSino Biologics Inc.

"We've been in a committed partnership with the NRC for almost a decade. It is perfect timing to leverage cutting-edge technology and resources from both sides that are critical to the development of Ad5-nCoV," says Xuefeng Yu, Chairman and CEO of CanSino Biologics Inc. "We are in this global public health emergency together, and a collaborative engagement could be the shortcut to help win this race against novel coronavirus disease."

Currently, the aim is for the various phases of Canadian clinical trials of Ad5-nCoV to be conducted in Canada over the course of the next year, under the authority of Health Canada. If trials are approved and demonstrate it is safe and effective, then a vaccine against COVID-19 may be available for Canadians sometime in 2021.

Leveraging key Canadian expertise


VIDO-InterVac researchers at the University of Saskatchewan

The NRC has also initiated a new collaboration with the University of Saskatchewan's Vaccine and Infectious Disease Organization-International Vaccine Centre (VIDO-InterVac). This research collaboration will leverage key Canadian research expertise and technology to advance development and production of a candidate COVID-19 antigen. The antigen in question has already been produced at laboratory scale, and animal studies at VIDO-InterVac are ongoing to determine the effectiveness of the laboratory-scale antigen.

The NRC will now explore the use of its proprietary HEK293 mammalian cells to develop a robust and efficient process to scale up production of the vaccine antigen for future pre-clinical and clinical studies.

Says Roman Szumski, Vice-President of Life Sciences at the NRC: "This is a time of increasing global uncertainty. At the NRC, we're working hard to be part of the solution by providing key Canadian expertise and facilities to address the real and potential impacts of COVID-19."

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