Rapid research response against highly pathogenic avian influenza launches to strengthen pandemic preparedness

The University of Toronto’s Emerging & Pandemic Infections Consortium (EPIC) has launched a rapid research response to address the public health risk posed by highly pathogenic avian influenza (HPAI).

The response provides $250,000 in funding to support five projects that aim to understand the fundamental biology of bird flu viruses, including their potential for human transmission, and to develop new methods for detection and outbreak management.

“EPIC’s unique ecosystem, comprising members with diverse expertise and perspectives, means that we are able to leverage talent quickly and prioritize work that will address the most complex and urgent infectious disease-related challenges,” says Scott Gray-Owen, EPIC’s academic director and professor of molecular genetics at U of T’s Temerty Faculty of Medicine.

HPAI viruses typically infect birds, but since 2022, there have been increasing reports of virus spillover to mammals, including widespread detection of HPAI in commercial dairy cows in the U.S. Recently, the U.S. reported its first deathof an infected person and a teen in British Columbia became critically ill with HPAI — the first human case in Canada.

The ability of HPAI viruses to jump between species greatly increases the risk of their transmission to and within human populations, raising concerns for a potential human outbreak.

One of the funded projects is led by Michael Norris, an assistant professor of biochemistry at Temerty Medicine, and will explore how the bird flu virus can infect different animals.

“We want to understand what is fundamentally different about HPAI that allows it to infect such a broad range of host species and why it’s so severe in some hosts but not others,” he says. “Once we understand the mechanisms of viral entry, we can develop methods to block it.”

His group will study naturally occurring mutations in a viral surface protein to narrow down which ones allow the virus to infect diverse hosts. Because this protein is essential for entering host cells, it is a major target for vaccine development. Norris’ work will also determine what parts of this protein elicit the best antibody responses, which will help inform better vaccine design.

Another project led by Samira Mubareka, a clinician scientist at Sunnybrook Research Institute, aims to better understand how HPAI virus subtypes differ in their ability to transmit in humans.

“One of the advantages of the EPIC HPAI program is access to the high containment facility needed to work with these viruses, which require a highly specialized and secure work environment,” says Mubareka, who is also an associate professor of laboratory medicine and pathobiology at U of T.

With over 50 subtypes of the H5N1 bird flu strain currently circulating, her group’s work in the Toronto High Containment Facility will be crucial to pinpointing which ones pose the greatest risk for a widespread human outbreak.

Two other projects are providing the critical information needed to mount an effect public health response against HPAI.

The first is led by Sharon Walmsley, a clinician scientist at University Health Network (UHN) and professor of medicine at U of T, and will screen high-risk individuals for evidence of HPAI infection to determine what proportion of infections are symptomatic versus asymptomatic.

The second project focuses on developing a serological assay, or blood test, that can detect antibodies against the bird flu virus and measure their effectiveness against viral infections.

“Serological assays help us figure out how many people in a population are exposed to the virus and existing levels of population immunity,” says Vanessa Allen, project lead and a medical microbiologist and infectious diseases physician at Sinai Health and UHN.

“Developing a serological test for a new pathogen requires coordinated efforts, bringing together people with different expertise and providing them access to the high containment facility.”

Allen, who is also an associate professor of laboratory medicine and pathobiology, notes that validation of the tests now will strengthen pandemic readiness by allowing labs to immediately start tracking infections and immunity during an outbreak.

To further bolster health system preparedness, UHN senior scientist Beate Sander is leading a project to develop computer models to predict how an HPAI outbreak might affect health care systems and resources. The project builds on her team’s previous work developing similar models during the H1N1 swine flu and COVID-19 pandemics.

“We will look at surveillance data, health administrative records of patients admitted to hospitals, pandemic literature on disease history from all over the world and come up with different scenarios of how an influenza pandemic could play out,” says Sander, who is also a professor at the Institute of Health Policy, Management and Evaluation at the Dalla Lana School of Public Health.

The models will be used to predict demand for resources — including medications, vaccines, hospital beds and ventilators — needed to cope with an HPAI outbreak. These forecasts can then be implemented into public health approaches, creating more resilient hospital- and community-based health systems.

“Our rapid research response program provides the capacity for investigators to establish critical capacities and provide key data that can be used to prepare for emerging threats, rather than scrambling to catch up once they arrive,” says Gray-Owen.

“This will position our experts to lead a response that will protect Canadians and the global community.”