Coronaviruses and Vaccine Design – A Conversation With Jason Kindrachuk
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Jason Kindrachuk is an assistant professor in the Department of Medical Microbiology & Infectious Diseases, University of Manitoba, Canada. He holds a Tier 2 Canada Research Chair in the molecular pathogenesis of emerging and re-emerging viruses.
Kindrachuk’s scientific expertise is focused on emerging virus pathogenesis and outbreak preparedness, particularly within vulnerable communities. Much of his research is directed towards the circulation, transmission and pathogenesis of emerging viruses that pose significant threats to human and animal health.
Technology Networks recently had the pleasure of interviewing Kindrachuk to learn more about his work with coronaviruses and the development of a vaccine candidate against the novel coronavirus, SARS-CoV-2.
Laura Lansdowne (LL): When did you begin working with coronaviruses and how did this work impact your approach to investigating the novel coronavirus SARS-CoV-2?
Jason Kindrachuk (JK): My first work with coronaviruses began in late 2013 following the emergence of Middle East respiratory syndrome coronavirus (MERS-CoV). I was working at the National Institutes of Health at the time, on emerging viruses and our facility quickly focused our efforts on trying to characterize the virus and identify possible candidates for drug repurposing – the use of licensed drugs for alternative approaches – as repurposing has been seen as a mechanism to circumvent the time to move a brand new drug from bench to bedside (typically a decade or more). My work really focused on trying to identify how this virus interacts with our cells during the course of infection by trying to determine how cells are “rewired” when the virus enters.
If we think about our cells from the standpoint of a building, we know that we need complex wiring and on/off switches to help make things work – lighting, security, emergency alarms, etc. Cells rely on this wiring and these switches to help make things work – to elicit responses and signals specifically when they’re needed. My work focuses on identifying which switches are turned on or off during infection and when exactly those events occur. Many of these events are regulated by enzymes called kinases, which turn the switches on or off. Kinase inhibitors are a specific drug class that has been a focus of drug development for cancer. However, we think that we might be able to find candidate drugs that could be repurposed for infectious diseases, like MERS or COVID-19. We were able to publish a few papers on this approach for MERS-CoV and have since used this type of research to investigate numerous viruses including Ebola virus, influenza viruses and orthopoxviruses, including monkeypox and variola virus.
When SARS-CoV-2, the virus that causes COVID-19, emerged at the end of 2019, there was little question that I would refocus my research program on this virus. By the time I returned from leading an emerging virus training program in Nairobi, Kenya, at the end of January, my work began on COVID-19. First as a co-applicant on an animal model development grant led by Dr Darryl Falzarano here at VIDO-InterVac, and since as a project leader here through a university partnership with my home institution, the University of Manitoba, along with my spouse Dr Kristen Kindrachuk, who is here as a project manager for COVID-19 work through a 1-year research leave from the University of Manitoba.
LL: The University of Saskatchewan (USask) and Infectious Disease Organization-International Vaccine Centre (VIDO-InterVac) have been involved in the development of a COVID-19 vaccine candidate, could you tell us more about the design of this vaccine?
JK: The vaccine being developed here at VIDO-InterVac is a protein subunit vaccine that is in the preclinical stages of development and has been their research focus since the earliest days of the pandemic, with Dr Falzarano leading this work internally. The protein subunit being used for the vaccine is comprised of a region of the spike protein, the viral protein that is responsible for initial interactions with our cells during infection. VIDO-InterVac is also testing the use of adjuvants for this vaccine. Protein subunit vaccines tend to not generate the same immune response activation as the complete virus so adjuvants can be added to these formulations to help initiate a more robust immune response to the vaccine – and hopefully the generation of a better protective response.
LL: Could you tell us more about the studies that have been conducted so far to determine the safety and efficacy of the vaccine candidate, at what stage of the development pipeline is the vaccine currently?
JK: Thus far, the vaccine was highly effective in generating protection in a ferret model of SARS-CoV-2 infection and testing of toxicology and safety are underway. While production delays on material for the vaccine slowed down some of the movement into human trials, VIDO-InterVac is hopeful that clinical trials in humans will start late this year.
LL: How has the COVID-19 pandemic impacted drug development efforts more generally – have you seen a significant difference in the way researchers are approaching drug discovery projects?
JK: COVID-19 has in many ways changed the calculus for drug discovery/development and testing. The emergence of a new virus for which we have no underlying immunity, no vaccines and no therapeutics has challenged us to our core. How quickly can we identify vaccines and therapeutics in the midst of a global public health crisis caused by a virus we’ve only just relatively met. Our collective response to this has been a testament to the versatility and tenacity of the entire research community – researchers, clinicians, technicians, healthcare and infrastructure support staff. Everyone has stepped up their efforts to help identify mechanisms that could help us streamline the process for identifying new drug and vaccine candidates. And the cornerstone of all of this has been that this has been a truly international response to an international crisis. Researchers have been collaborating across international and political boundaries on this from day one and continue to share data in real time with one another utilizing social media as well as traditional platforms for this. This has been one of the biggest differences from past health crises as we now have the technology to communicate across the globe instantaneously which has fostered countless new collaborations and potential solutions to this pandemic.
Jason Kindrachuk was speaking to Laura Elizabeth Lansdowne, Senior Science Writer for Technology Networks.
