COVID-19 response: Vaccines and therapeutics

 

Canada is home to some of the most skilled and recognized researchers in the world, who are working hard to support Canada's efforts to fight the COVID-19 pandemic. In an effort to slow and eventually stop the spread of the virus, the NRC is working with partners to advance research and technology development for therapies and vaccines to treat and prevent COVID-19.

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

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.

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Dr. Lakshmi Krishnan, Acting Vice President of the NRC's Life Sciences division.

"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

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 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.

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 by the end of 2020.

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.

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.

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.

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."

 

Nanotechnology Research Centre joins COVID-19 Consortium

The NRC has joined a consortium of institutions that are merging supercomputing resources to use high-end computing power to study COVID-19.

A research team comprised of Dr. Sergey Gusarov from the NRC's Nanotechnology Research Centre and Dr. Stanislav Stoyanov of Natural Resources Canada have been awarded the use of top-level computing systems to accelerate the fight against COVID-19.

Dr. Gusarov's and Dr. Stoyanov's project titled "The Competition of Antiviral Drugs with ATP to Inhibit the SARS-CoV-2 RNA-dependent RNA Polymerase: A Key to Enhanced Drug Screening" aims to demonstrate a new computer calculation for the enhanced screening of drugs. Their competitive screening approach would allow a direct comparison of a drug's behaviour to better understand the reactions that will take place in the body.

The Haswell and KNL Compute Nodes that will be used for the project come courtesy of the Natural Sciences and Engineering Research Council of Canada and the Edinburgh Parallel Computing Centre at UK Research and Innovation. To achieve their research goals, Dr. Gusarov and Dr. Stoyanov will use the open-source software tool called "Reference Interaction Site Model (RISM) for High Performance Computing (HPC)," which was developed at the NRC in collaboration with the University of Alberta.

This collaboration has been made possible through the COVID-19 High Performance Computing (HPC) Consortium, which encompasses computing capabilities from some of the most powerful and advanced computers in the world. The Consortium aims to bring together the federal government, industry, and academia to empower researchers to accelerate understanding of the COVID-19 virus and the development of treatments and vaccines to help address infections. The supercomputers used will allow the researchers to process large amounts of data and zero in on the coronavirus at the atomic level.

Since the consortium has been formed, the researchers have succeeded in extending the study by establishing a connection with existing NRC programs such as AI4Design and the Clean Energy Materials Program. Now the study is focussed on two directions:

  • applying the NRC's open-source "RISM for HPC" tool to study COVID-19; and
  • advancing new quantum chemistry-based descriptors for machine learning drug development.

These extensions will allow the use of the synergy of multiscale modeling approach, and the first results will be published soon.

 

NRC's publication on COVID-19 garners worldwide attention

Experts at the Nanotechnology and Human Health Therapeutics research centres recently published a highly consulted article on the impact that the SARS-CoV-2 infection has on the central nervous system (CNS).

The article, "Severe acute respiratory syndrome coronavirus 2 may be an underappreciated pathogen of the central nervous system" is featured in Neurology, the official journal of the European Academy of Neurology, and is among the first COVID-19-related publications produced from the NRC. This article is also one of the first by an all-Canadian group to be accessed at such a high rate after publishing. The following experts from the NRC collaborated on the project: Alam Syed Benazir, Steven Willows, and Marianna Kulka from Biomedical Nanotechnologies; and Jagdeep Sandhu from Preclinical Imaging and Microscopy.

The paper has already been accessed more than 1,400 times worldwide and has received considerable attention from COVID-19 researchers.

In the publication, the researchers outline that although COVID-19 was first described as a respiratory disease, new data shows that SARS‐CoV‐2 can infect almost every organ, resulting in an ever‐increasing list of symptoms. In particular, neurological symptoms and disturbances in the CNS are common in many COVID-19 patients and may be a predictor of disease severity. This review summarizes some of the most recent data on COVID-19-associated neurological disease. It is now clear that SARS‐CoV‐2 has the potential to infect the central nervous system and cause long‐term neurological damage in COVID-19 patients.

This deeper understanding of the virus, described by NRC researchers, is helping pave the way for future research in this area and enabling the development of better therapeutic strategies.