How does the body fight COVID-19? U of T researcher's work could aid vaccine development

Jen Gommerman, an immunologist at the University of Toronto, wants everyone to know one important point about the COVID-19 pandemic:  The human immune system is working to fight off this novel coronavirus.  

Many thousands of people have died from the virus. But many more thousands have contracted it and survived. That is because when the virus first enters your body, usually through your nose or mouth, it triggers the immune system to send antibodies in response. Antibodies are proteins in your blood that your body uses to fight infection. In diseases such as chicken pox, the antibodies usually prevent you from getting the illness again. The formal term for the generation of antibodies is a “humoral immune response.” 

But COVID-19 – the illness caused by the SARS-CoV-2 virus – is puzzling scientists with some challenging questions: If a person recovers from COVID-19, will the antibodies keep that person from being infected again? Why don’t some people show symptoms? What happens as soon as the virus enters the body? 

Gommerman, a professor in the department of immunology in the Faculty of Medicine, has received support from the Ontario COVID-19 Rapid Research Fund to conduct research in collaboration with an interdisciplinary team of scientists to answer these and other questions.  

She emphasizes that the greatest challenge in understanding anything to do with COVID-19 is the fact that it is new.  

“Understanding how SARS –CoV-2 induces a humoral immune response is vital to scientists eventually developing a vaccine,” she says. “But the world has only known about this virus since December or January. It is brand new. The science community doesn’t fully understand yet how the immune system responds to the virus. 

“So my team’s work will shed some light on that, which, in turn, could help with the development of a vaccine.” 

The province’s rapid research fund is also supporting the work of Jean-Philippe Julien, senior scientist in molecular medicine at the Hospital for Sick Children and an assistant professor in biochemistry and immunology at U of T.  His project will use molecular technology to develop a “potent and broad” antiviral treatment. 

As for Gommerman, she will be developing an assay (the scientific term for a test or experiment) to identify antibodies in saliva in the hopes of better understanding the early immune response when the virus enters the oropharyngeal tract (a part of the throat behind the mouth and nasal cavity).  

Like so much of the COVID-19 research being conducted now, the work being spearheaded by Gommerman is a collaboration with a number of other scientists at U of T and the university’s partner hospitals.  

Gommerman’s research into saliva, for example, will be compared with assays being done by Anne-Claude Gingras, a senior investigator at Sinai Health’s Tanenbaum Lunenfeld Research Institute and a professor of molecular genetics at U of T.  

Gingras has led the development of a blood test that can detect antibodies in the immune system of infected patients. The test has the potential to enable hospitals and other institutions to screen up to 10,000 samples at once.  This type of analysis is called “serosurveillance” – the study of blood serum, especially as it relates to the work of the immune system response to pathogens entering the body.  

“Serosurveillance is an important weapon in our fight against COVID-19,” Gommerman says. “It has the power to tell us what is the true scope of the pandemic.  This is what the blood experiments at Mount Sinai get us. 

“For the saliva experiments, we will learn more about what is happening early in the immune response in asymptomatic patients in the oropharyngeal tract where the virus is first introduced. This has the potential to reveal what aspects of the immune response might confer protection to those people who never show symptoms or only show mild symptoms.” 

Key to understanding the early immune response is a collaboration with Darrell Tan, an infectious diseases physician and clinician-scientist at St. Michael’s Hospital. Tan, who is also an assistant professor in U of T’s Faculty of Medicine and at the Institute of Health Policy, Management and Evaluation at the Dalla Lana School of Public Health, is enrolling 1,000 subjects, via contact tracing, who have been linked to patients infected with COVID-19. Tan and his team will test the saliva of these people regularly over a number of weeks.  

The contacts are called a “ring of associates.”  

“Because the people in that ring have a higher chance of contracting COVID-19 than the general public, we will presumably have people who are just getting infected,” says Gommerman. “This will allow us to learn why some people don’t show symptoms but still have the illness and how the early immune response actually works.” 

Both Gommerman and Gingras are using proteins produced by U of T’s James Rini, professor in the departments of molecular genetics and biochemistry.  The proteins are highly purified pieces of the SARS-CoV-2 virus that are used as bait to catch antibodies in the saliva or in the blood so that the researchers can measure them.  

“Without Jim’s work on these proteins, we wouldn’t be able to go further in our research,” says Gommerman. “He’s been studying coronavirus proteins since SARS first hit North America in 2003. The science community doesn’t know nearly as much about coronaviruses as we do, for example, influenza.  

“We owe a lot to researchers like Jim who have been building up a knowledge base about coronaviruses.  We’re relying on them now.” 

Further to the collaborative nature of the research, Gommerman’s team is using saliva samples from patients who have had the virus, and who have recovered. The samples were collected by: Mario Ostrowski, a professor in the departments of medicine, immunology and laboratory medicine and pathobiology at U of T; Allison McGeer, director of the Infectious Diseases Research Unit at Mount Sinai Hospital and a U of T professor in the departments of medicine and laboratory medicine and pathobiology (LMP), as well as at the Dalla Lana School of Public Health; and Samira Mubareka an assistant professor in the department of laboratory medicine and pathobiology who is at Sunnybrook Health Sciences Centre. 

The multidisciplinary nature of the research is what enabled Gommerman to pivot from her usual work on autoimmune diseases, especially multiple sclerosis, and gut immunology. The ability to draw on the skills and experiences of members of her team was also key. 

“Our research associate, Dr. Olga Rojas, had worked on saliva antibodies to a disease called rotavirus when she was studying in Colombia, South America.” 

Also key to the pivot were three first-year doctoral students – Baweleta Isho, Annie Pu and Michelle Zuo.  

“I didn’t want to pull more senior students from their doctoral work, so I asked these first-year students to help with the work,” Gommerman says. “They’ve been amazing, as well as our project manager, Dr.Gary Chao, who organized all the samples and made sure we were compliant from a biosafety and ethics perspective. This was urgent work and they all rose to the occasion under a lot of pressure.”  

with files from Amanda Ferguson