Emerging and Pandemic Infections Consortium

Topic

Sunnybrook Health Sciences Centre

Hospital for Sick Children

Unity Health

Health

Subheadline

Renewal of the 20-year-old facility, which allows researchers to study high-risk pathogens, will provide increased capacity to develop new vaccines and therapeutics

Canada’s ability to respond rapidly to emerging infectious diseases is taking a step forward with a $9.9-million investment from the Ontario government to support critical research infrastructure updates to the Toronto High Containment Facility (THCF), which houses the largest containment level 3 lab in the province.

The facility, located at the University of Toronto, is specially equipped to allow researchers to study high-risk pathogens, such as SARS-CoV-2, HIV, tuberculosis and mpox, in a safe and secure way.

Research undertaken at the current facility has advanced our understanding of infectious diseases and strengthened our ability to respond to emerging health threats.

“The THCF strengthens Ontario’s position as a prime location for globally leading companies and top talent to discover and commercialize cutting-edge technologies, while improving our preparedness for future health challenges,” says Leah Cowen, U of T’s vice-president, research and innovation, and strategic initiatives. “The updated facility will enhance Canada’s health infrastructure and health security, and ensure that Canadian researchers are trained and ready to respond to emerging infectious diseases.”

The provincial funding builds on a previous $35-million investment from the Canada Foundation for Innovation to support efforts to revitalize and expand the THCF and to transform it into the largest academic high-containment research centre in Canada.

The renewal of the 20-year-old facility will provide increased capacity to use state-of-the-art approaches supporting academic research projects as well as collaborative industry-led efforts to develop new vaccines and therapeutics for Canadians. The new provincial investment will also allow the facility to meet the growing demand from industry and public sector partners while maintaining ongoing research projects and an agile responsiveness to future outbreaks.

“The new THCF will allow our researchers to work on the most urgent infectious disease threats, provide greater opportunities to engage with government agencies and industry partners, and allow us to provide unique training opportunities for the next generation of infectious disease leaders, building a strong foundation for Canada’s response to future outbreaks,” says Scott Gray-Owen, academic director of the THCF and a professor of molecular genetics in U of T’s Temerty Faculty of Medicine.

The provincial support is part of a suite of investments through the Ontario Research Fund and the Early Researcher Awards that also include support for quantum and artificial intelligence projects at U of T. Support has also been extended to advance an infrastructure renewal of the province’s Advanced Research Computing (ARC) systems, including U of T’s Niagara ARC supercomputer, used by researchers across the country.

As the only high containment facility of its kind in the Greater Toronto Area, the THCF is a unique asset to the life sciences ecosystem in the region, which is home to 55 per cent of Canada’s pharmaceutical companies. The modernized facility will be able to support greater engagement with industry partners to advance made-in-Ontario therapeutics such as the experimental drug paridiprubart from Markham-based Edesa Biotech, which is currently being tested in a Phase 3 clinical trial to treat acute respiratory distress syndrome, a common complication from COVID-19 or influenza infections.

In addition to industry partners, the THCF has been used by federal and provincial agencies including the Public Health Agency of Canada, Bank of Canada, Rogers Hixon Ontario Human Milk Bank and Ontario Ministry of Natural Resources and Forestry.

The THCF renewal will also be undertaken in collaboration with U of T’s hospital partners: The Hospital for Sick Children, Sinai Health, Sunnybrook Health Sciences Centre, Unity Health Toronto and University Health Network. Construction of the facility has begun but the university is seeking additional funding to complete the project.

Based at the Temerty Faculty of Medicine, the THCF is the cornerstone of the Emerging and Pandemic Infections Consortium, a U of T institutional strategic initiative that brings together the university and Toronto Academic Health Science Network (TAHSN) hospital partners to drive innovative approaches to infectious diseases and prepare for future pandemics. It is also a key infrastructure resource for the Canadian Hub for Health Intelligence and Innovation in Infectious Diseases (HI3) which was established through the Canada Biomedical Research Fund. The hub brings together over 90 partners across several sectors to bolster Canada’s biomanufacturing capacity to ensure a fast and co-ordinated response to future pandemics and infectious threats.

The revitalized THCF will also have the capacity to train more than 100 new highly qualified professionals over a five-year period with industry-relevant skills, including manufacturing practices and vaccine and therapeutics development.

At the beginning of the COVID-19 pandemic, the THCF was the first lab in Canada – and one of the first in the world – to isolate the new coronavirus in March 2020. The facility and its highly trained staff played a key role in accelerating research breakthroughs that guided the pandemic response including, for example, methods to allow safe reuse of personal protective equipment in health-care settings and to ensure safe human milk banking for premature infants.

The THCF was also a core element of EPIC’s mpox rapid research response, housing a biobank of samples from patients with mpox which are being used by researchers to better understand the dynamics of viral shedding and other important questions about the disease.

In addition to a larger physical space, the updated facility will include a state-of-the-art high containment insectary to enable research on mosquito-borne viruses like Chikungunya, dengue, Zika and yellow fever. With its modular design and enhanced safety features, the new facility will also be better positioned to respond to emerging pathogens like highly pathogenic avian influenza.

Breast milk may have protective effects against COVID-19: Researchers

Christopher.Sorensen — Mon, 29 Jan 2024 18:38:03 +0000

Breast milk may have protective effects against COVID-19: Researchers

Christopher.Sorensen Mon, 01/29/2024 - 13:38

Cutline

Samantha Ismail led a study by researchers at U of T and its partner hospitals that looked for SARS-CoV-2 antibodies in human breast milk (supplied image)

Topic

COVID-19

Sunnybrook Health Sciences

Laboratory Medicine and Pathobiology

Vaccines

Subheadline

“COVID-19 vaccination and infection result in antibodies in human milk that have neutralizing capacity"

The COVID-19 pandemic was an especially harrowing time for pregnant people and new parents.

The uncertainties about how the new coronavirus could affect a pregnant person and their developing fetus – not to mention being cut off from support networks – left many expecting parents feeling isolated and anxious.

“It was a very surreal time,” says Jenny Doyle, a Toronto mom who gave birth to her first child, Elliott, in 2020 and spent hours researching how the first vaccines made available the following year might affect her and her child. “At the time, vaccines for infants were still so far away. I remember hoping that some of the protection I’d received from my vaccine would pass through to Elliott.”

Now, new findings from a study led by researchers at the University of Toronto and its partner hospitals suggest that is the case.

Published in the American Journal of Clinical Nutrition, the study looked for antibodies against SARS-CoV-2 in breast milk from three different cohorts: individuals who contracted COVID-19 while pregnant or nursing, routine milk bank donors and individuals who received two doses of the COVID-19 vaccine while pregnant or nursing.

The researchers detected antibodies in breast milk from roughly half of the people in the COVID-19 positive cohort. That’s compared to less than 5 per cent of routine milk bank donors, who did not have any known exposures to COVID-19. In the vaccinated cohort, they found that antibodies levels were higher in people who had received the Moderna vaccine compared to those who had received the Pfizer-BioNTech vaccine. Unexpectedly, people who had shorter intervals between their first and second doses had higher antibody levels than those who waited longer between their immunizations.

“That finding definitely surprised me,” says Samantha Ismail, the study’s first author who completed her master’s degree in the lab of Deborah O’Connor, the Earle W. McHenry Professor and chair of Temerty Medicine’s department of nutritional sciences. “In [blood] serum, it’s the other way around where longer intervals between doses typically result in higher antibody levels, suggesting that something different is happening in this lactating population.”

In addition to Ismail and O’Connor, the study was led by Sharon Unger, medical director of the Roger Hixon Ontario Human Milk Bank at Sinai Health and a U of T professor of medicine and nutritional sciences, and Susan Poutanen, microbiologist and infectious disease consultant and Sinai Health and U of T associate professor of laboratory medicine and pathobiology.

The team took the study one step further by showing that some breast milk samples could prevent SARS-CoV-2 from infecting cells in a lab setting. Within the COVID-19 positive cohort, milk that contained antibodies against the virus were more likely to be neutralizing and immunization with the Moderna vaccine was associated with a stronger neutralizing capacity than the Pfizer-BioNTech vaccine.

The researchers also found a small but significant number of breast milk samples that prevented SARS-CoV-2 infection despite having undetectable levels of antibodies, suggesting that there could be other components in human milk that are active against SARS-CoV-2.

While these findings provide strong evidence to support the potential protective effects of human milk, Ismail cautions that the study alone is not enough to prove that breast milk provides tangible protection against COVID-19.

“COVID-19 vaccination and infection result in antibodies in human milk that have neutralizing capacity, but we don’t know for sure how the neutralizing capacity seen in the lab translates to protection in infants,” says Ismail, who is now a second-year medical student at U of T.

She points out that previous studies have shown a clear protective effect of antibodies in human milk against other viruses like enterovirus and rotavirus. To date, such studies have not been done with COVID-19.

Even so, the findings provide reassuring news to parents like Doyle, who breastfed her son longer than she had intended to ensure that he was still getting breast milk when she received her second COVID-19 vaccine.

“Trying to figure out how to protect this tiny being in that scary and bleak time, I was grasping at every little piece of information and whatever little piece of hope we had.”

The study was supported by the Canadian Institutes for Health Research and was a collaboration between the department of microbiology at Sinai Health System/University Health Network, the Roger Hixon Ontario Human Milk Bank at Sinai Health System and the Toronto High Containment Facility, where the live SARS-CoV-2 neutralization studies were completed.

It involved contributions from several members of the Emerging and Pandemic Infections Consortium, a U of T institutional strategic initiative. In addition to O’Connor, Poutanen and Unger, they include Scott Gray-Owen, of Temerty Medicine’s department of molecular genetics, Samira Mubareka, of Sunnybrook Health Sciences Centre and Temerty Medicine’s department of laboratory medicine and pathobiology, and Jennie Johnstone and Allison McGeer – both of Sinai Health and Temerty Medicine’s department of laboratory medicine and pathobiology.

U of T PhD student uses synthetic biology to create low-cost diagnostic tools

Christopher.Sorensen — Wed, 25 Oct 2023 14:55:23 +0000

U of T PhD student uses synthetic biology to create low-cost diagnostic tools

Christopher.Sorensen Wed, 10/25/2023 - 10:55

Cutline

Justin Vigar, pictured here in a lab in South America, is developing paper-based diagnostics like the paper chip shown on the right, where each dot represents a different test (supplied image)

Topic

Leslie Dan Faculty of Pharmacy

Graduate Students

Subheadline

Justin Vigar and his colleagues are creating a customizable, paper-based platform to rapidly screen for COVID-19 and other infectious diseases

“Synthetic biology” might sound like a contradiction in terms, but University of Toronto graduate student Justin Vigar believes it can improve the health and lives of people around the world.

A relatively new field of research, synthetic biology applies engineering principles to recreate fully functional biological systems. In Vigar’s case, he’s using the approach to develop rapid, low-cost diagnostic tools to combat infectious diseases as the recipient of a doctoral award from the Emerging and Pandemic Infections Consortium (EPIC) – one of several U of T institutional strategic initiatives.

Today, the gold standard for diagnosing many infectious diseases is a technique called real-time reverse transcription-quantitative PCR (RT-qPCR), which is both sensitive and specific enough to detect small amounts of a particular microbe in a patient sample. However, the process is complex, requires expensive equipment and materials, and must be carried out by highly trained personnel.

“We talk a lot about South America and other countries in the Global South but in most areas in Canada, including rural Alberta where I grew up, there’s no access to RT-qPCR,” says Vigar, a fourth-year PhD student who is working with Keith Pardee, an associate professor in the Leslie Dan Faculty of Pharmacy.

The lack of access to RT-qPCR testing was especially apparent during the COVID-19 pandemic when many low- and middle-income countries struggled to track the spread of SARS-CoV-2 within their borders because they did not have the infrastructure, expertise and resources to conduct timely RT-qPCR tests for their citizens. Rapid antigen tests helped fill the void, but they aren’t as sensitive and cannot be scaled up easily to process hundreds of samples at once.

“We wanted to fill that gap by building really accessible tools that could do rapid screening for COVID-19 and other infections – something that would be a midway between a rapid antigen test and RT-qPCR,” says Vigar.

To that end, he and his lab colleagues are creating a customizable, paper-based platform that uses pocket-sized slips of paper with embedded genetic circuits. The circuitry is built by freeze-drying proteins and other molecular components, which function as amplifiers and sensors, directly onto the paper. Patient samples are minimally processed to extract the genetic material and applied directly to the paper. If the patient sample contains genetic materials from the pathogen of interest, it will trigger the circuitry to switch on and produce a colour change on the paper, which can be spotted by the naked eye.

Pardee’s team has already proven the effectiveness of their paper-based diagnostic tool in enhancing disease surveillance during Brazil’s 2015-2016 Zika virus outbreak and, more recently, during the COVID-19 pandemic. Now Vigar is working with collaborators in other Latin American countries and India to expand use of the diagnostic tool to monitor other infectious diseases such as dengue fever and leishmaniasis, which is caused by the Leishmania parasite.

“We have the system working very well in Toronto and a couple of our collaborating countries but the challenge now is sourcing the materials to embed onto the paper and scaling up in other countries,” Vigar says.

While it’s easy for Vigar to get the components and build the paper devices in Toronto and ship them to collaborators around the world, his ultimate goal is to empower them to manufacture and distribute the tools locally.

“We need to work with researchers in other countries to build a network that will give them access to these reagents and materials so they aren’t relying on us to ship it to them. Then they’ll be able to build their own pipelines to detect the pathogens and diseases that they’re interested in.”

Vigar was in Chile for two weeks this past summer to help local researchers to test the reproducibility of their own paper tests. Pardee’s lab also recently hosted two visiting students from Universidad de Los Andes in Columbia to learn the process for building the low-cost devices.

Beyond monitoring infectious diseases in humans, Vigar says the paper-based platforms are being used to answer other important questions – for example, tracking the spread of an agricultural pest or the movements of an endangered species.

Vigar’s passion for synthetic biology and ensuring equitable access to new biotechnologies extends beyond the lab.

He is an active delegate to the United Nations Convention on Biodiversity (UNCBD), which includes two international agreements on biosafety and profit sharing related to synthetic biology and biotechnology. As an attendee at the UNCBD Conference of the Parties (COP) in Sharm El-Sheikh, Egypt in 2018 and in Montreal in 2022, he educated attendees about synthetic biology and shared his perspective on how low-cost diagnostics can improve the lives of people around the world.

“These technologies are so powerful but they’re limited in where and how they’re used. We want to make it more accessible – and if we work collaboratively toward that goal, it’s going to benefit so many more people.”

Study uncovers how the gut's microbiome boosts immune system development

Christopher.Sorensen — Wed, 11 Oct 2023 17:02:48 +0000

Study uncovers how the gut's microbiome boosts immune system development

Christopher.Sorensen Wed, 10/11/2023 - 13:02

Cutline

Arthur Mortha, left, and Pailin Chiaranunt led research that revealed new insights about how gut microbes influence immune system development (photo by Mark Bennett)

Topic

Subheadline

“The gut is probably one of the most dynamic ecosystems in the body because you essentially have the outside environment inside of you”

A study is shedding new light on how the gut’s microbial communities contribute to a well-functioning immune system and defend against harmful pathogens.

The findings, published in the journal Science Immunology, include important insights on how monocytes, a type of white blood cell, transform into macrophages, which play a key role in eliminating foreign microbes and initiating an immune response.

Lead author Pailin Chiaranunt, a PhD student in the department of immunology at University of Toronto’s Temerty Faculty of Medicine, says she first learned about the microbiome as an undergraduate student and then fell in love with immunology as a research technician.

“The fact that there are these vast ecosystems of bacteria, fungi, viruses and other microbes living inside us really reshaped the way I see the human body,” Chiaranunt says.

In the study, the researchers turned their attention to macrophages, key immune cells whose job is to gobble up cellular debris and foreign microbes and kick start the immune response.

They found that the transformation of monocytes, a type of white blood cell, into macrophages in the gut requires both a diverse microbiome and a host factor called CSF2. Then, in a series of experiments, Chiaranunt and her colleagues identified the microbial factor driving macrophage development as ATP, a molecule that is used as energy currency across all forms of life.

Their work also uncovered how microbial and host factors work together to support a robust immune environment in the gut: ATP produced by resident bacteria in the gut activates immune cells within a network of small, lymph node-like structures across the intestinal tract. These cells then produce the host factor CSF2 which spurs monocytes in the structures to become response-ready macrophages.

The researchers further showed that the macrophages born from this pathway have high metabolisms and as a result, produce a lot of antimicrobial chemicals called reactive oxygen species. The abundance of these chemicals, in turn, contribute to the immune system’s ability to ward off microbial intruders in the gut.

“That was a really cool finding because it suggests a new way in which microbial metabolism can directly impact immune cell metabolism,” says Chiaranunt, who recently defended her PhD thesis and is preparing to start a postdoctoral fellowship at the University of California, San Francisco.

The collection of microorganisms that live in and on our bodies plays a critical role in health and disease. Certain microbiome features – for example, whether there is more of one species or less of another – have been linked to a variety of health outcomes, from autoimmune and mood disorders to cancer risk and treatment response.

Chiaranunt says her interest in how the microbiome and immune system interact with each other, particularly in the gut, led her to U of T to pursue a PhD with Arthur Mortha, an associate professor of immunology in the Temerty Faculty of Medicine who studies the crosstalk between the immune system and gut microbiome.

“The gut is probably one of the most dynamic ecosystems in the body because you essentially have the outside environment inside of you,” Chiaranunt says. “There’s a lot of work the immune system must do to maintain a balance between tolerating helpful microbes, food and other outside factors, and being able to mount an effective defence against pathogens like salmonella that might show up.”

In addition to other members of Mortha’s lab, the study also included collaborators Slava Epelman, a scientist at the Toronto General Research Institute, University Health Network and clinician scientist in U of T’s department of medicine in the Temerty Faculty of Medicine, and Thierry Mallevaey, an associate professor of immunology in the Temerty Faculty of Medicine. Mortha, Epelman and Mallevaey are all members of the Emerging and Pandemic Infections Consortium, a U of T Institutional Strategic Initiative focused on developing innovative responses to infectious threats.

While other studies have also found a link between the microbiome and macrophage development, the researchers’ recent paper is one of the first to uncover how gut bacteria trigger white blood cells to become macrophages. The identification of CSF2 as a key contributor to that process also highlights the potential of CSF2-targeting treatments to modulate the immune response in people with autoimmune disorders and inflammatory bowel disease.

“Our results bring us a big step closer to understanding the biochemical language spoken by the microbiota,” says Mortha. “Assembling a comprehensive dictionary for this language will help us to interpret when and why friendly and offensive messages are used by gut microbes to communicate with our immune system.”

Research may explain why men are more likely to experience severe cases of COVID-19

Christopher.Sorensen — Tue, 03 Oct 2023 15:11:29 +0000

Research may explain why men are more likely to experience severe cases of COVID-19

Christopher.Sorensen Tue, 10/03/2023 - 11:11

Cutline

Haibo Zhang, a researcher at Unity Health Toronto and U of T, led pre-clinical research that suggests why males are more likely to experience worse outcomes from COVID-19, opening the door to potential new treatments (photo by Julia Soudat)

Topic

Sunnybrook Health Sciences

Hospital for Sick Children

Unity Health

Graduate Students

St. Michael's Hospital

Subheadline

Pre-clinical study points to ACE2 protein as a key contributor to the differences in COVID-19 outcomes between males and females

A new study by a team of researchers at the University of Toronto’s Emerging and Pandemic Infections Consortium (EPIC) has uncovered biological reasons underlying sex differences in COVID-19 outcomes, offering a promising new strategy to prevent illness.

The pre-clinical research, published in the journal iScience, has yet to be replicated in humans, but points to the ACE2 protein as a key contributor to differences in COVID-19 outcomes between males and females.

During the early days of the pandemic, clinicians noticed that males were more likely than females to be hospitalized or admitted to the ICU or to die from COVID-19 despite having similar infection rates.

This pattern held true across all age groups and in countries around the world.

“COVID-19 severity and mortality are much higher in males than in females, but the reasons for this remain poorly understood,” says study senior author Haibo Zhang, a staff scientist in the Keenan Research Centre for Biomedical Science at St. Michael’s Hospital, Unity Health Toronto, and a professor of anesthesiology and pain medicine, and physiology in U of T’s Temerty Faculty of Medicine.

“That was the driving force for our work.”

The study was a collaborative effort through EPIC, a U of T institutional strategic initiative that involves five hospital research partners – the Hospital for Sick Children (SickKids) Research Institute, Lunenfeld-Tanenbaum Research Institute at Sinai Health, Sunnybrook Research Institute, Unity Health Toronto and the University Health Network (UHN) – to facilitate an integrated and innovative response to high-risk, high-burden infectious diseases.

From left: PhD student Jady Liang, co-lead author of the study and Professor Haibo Zhang (photos supplied)

Located on the cell’s outer surface, ACE2 plays an important role in controlling blood pressure and inflammation and protecting organs from damage caused by excess inflammation. During a SARS-CoV-2 infection, the coronavirus spike protein locks on to ACE2 to enter the cell.

The gene encoding the ACE2 protein is located on the X chromosome, which means that females have two copies of the gene and males only have one.

In times of health, the extra copy of the gene for ACE2 doesn’t appear to make a difference – Zhang and his team found similar levels of ACE2 protein in healthy males and females.

Following a SARS-CoV-2 infection, however, they observed a dramatic decrease in ACE2 in males while levels remained consistent in females, suggesting that the additional copy of the ACE2 gene on the X chromosome is helping to compensate and maintain high protein levels in females.

The changes in ACE2 levels were also correlated with a drop in estrogen hormone signalling in males, which could also contribute to the sex-specific differences in COVID-19 outcomes.

To test whether low levels of ACE2 were responsible for the more severe outcomes seen in males with COVID-19, the researchers devised a therapeutic approach using an inhaler to deliver lab-made ACE2 proteins directly into the lungs. Males who received a daily puff of ACE2 after SARS-CoV-2 infection had less virus in their lungs, less lung injury and higher levels of estrogen signalling.

Together, these results paint a clearer picture of how the extra copy of the ACE2 gene and higher estrogen levels in females work together to protect them from experiencing more severe COVID-19.

“A common misconception is that an increased presence of ACE2 receptors would result in a higher infection rate,” says Zhang.

“However, the enhanced activation of ACE2 in females actually serves as a compensatory mechanism during infection that’s aimed at safeguarding the lungs and other vital organs from potential damage.”

In males who lack the second copy of the gene, much of the existing ACE2 gets co-opted by SARS-CoV-2 during an infection. As a result, there is not enough of the protein to fulfil its usual functions of tamping down inflammation and preventing organ damage.

The extra dose of ACE2 delivered by inhaler serves as a decoy to glom onto the coronavirus, thereby preventing it from entering cells while also keeping the native ACE2 proteins free to exert protective effects.

Beyond the thrill of discovery, Zhang says he is excited by the potential implications of these findings, which are the first to demonstrate the effectiveness of inhaling ACE2, on preventing and treating COVID-19 in humans.

He imagines a scenario where people who are entering high-risk situations – boarding an airplane or attending a large in-person conference, for example – might take a puff of ACE2 to protect their lungs from the virus. Similarly, the treatment could also be given to people after infection to reduce the risk of hospitalization and death.

“By using the inhaler, ACE2 remains in the lungs at a sustained, low concentration over an extended period, where it can neutralize the virus even before it enters into our cells. We anticipate that our research will motivate individuals to contemplate this faster and more efficacious strategy for both prevention and treatment of COVID-19 in humans,” says Zhang.

Zhang worked with fellow researchers Samira Mubareka (Sunnybrook, Temerty Faculty of Medicine), Theo Moraes (SickKids, Temerty Faculty of Medicine) and Mingyao Liu (UHN, Temerty Faculty of Medicine). Much of their work took place in the Toronto High Containment Facility (THCF), which is the only containment level 3 research lab in the Greater Toronto Area and the largest in the province.

Having access to the THCF allowed Zhang and his team to pivot quickly during the early months of the pandemic and apply their expertise in lung physiology and disease to answering rapidly emerging questions about COVID-19.

Jady Liang, the co-lead author of the new study, had just started her PhD with Zhang when the pandemic started. She recalls the stress and intensity of training and working in the THCF during that time but credits EPIC staff and other THCF users with helping her become comfortable with the processes and protocols.

“It was a lot of hard work from everyone on the team during the pandemic, especially during the first wave,” says Liang, who is now a fourth-year PhD student in the department of physiology.

“We need a lot of people with expertise in different fields to work together so that we can advance and be prepared for the next pandemic.”

The study received support from the Canadian Institutes of Health Research, among others.

Research shows how boosting immune memory could help develop improved flu vaccine

siddiq22 — Thu, 11 May 2023 20:33:55 +0000

Research shows how boosting immune memory could help develop improved flu vaccine

siddiq22 Thu, 05/11/2023 - 16:33

Cutline

PhD student Karen Yeung is one of the recipients of the inaugural EPIC Doctoral Awards for her work on boosting immune memory to enhance protection against influenza (supplied photo)

Topic

EPIC

Karen Yeung is no stranger to outbreaks of respiratory infections. As a child growing up in Hong Kong, she lived through the first SARS outbreak in 2003 and witnessed the city dealing with repeated threats of bird flu in the years that followed.

Twenty years later, in the midst of a global pandemic caused by SARS-CoV-2, the fourth-year PhD student in the department of immunology at the University of Toronto's Temerty Faculty of Medicine is leading critical research to understand how our immune systems respond to influenza infection – and how we might be able to leverage that knowledge to create a long-lasting, universal flu vaccine.

Yeung is one of 31 recipients of the inaugural Emerging and Pandemic Infections Consortium (EPIC) Doctoral Awards, which supports outstanding students pursuing infectious disease research.

“Current flu vaccines work by inducing an antibody response against a specific component of the influenza virus, but this viral component mutates very quickly every year. This means that the antibodies that you make against this year’s flu vaccine likely won’t match the strain of flu that we’ll see next season,” says Yeung, who is supervised by Tania Watts, a professor of immunology at U of T who holds the Canada Research Chair in anti-viral immunity.

Immune cells called memory CD8+ T cells might hold the key to unlocking broad protection against multiple flu strains. These immune cells retain a memory of a pathogen long after the initial infection, which allows the body to quickly mount a powerful immune response the next time it encounters that pathogen. And unlike the antibodies generated from a flu vaccine, memory T cells recognize parts of the influenza virus that are more likely to remain unchanged between strains and from one year to another.

Previous work from Watts’ lab was the first to show that a protein receptor on CD8+ T cells called 4-1BB is an important player in the formation of memory T cells after a flu infection. 4-1BB is part of a communications cascade that relays cues to regulate the immune system. Yeung’s doctoral research aims to uncover how this pathway is turned on to produce memory CD8+ T cells.

“We’re really interested in how cells can communicate to each other through the language of receptors like 4-1BB and signaling,” Yeung says.

“When you have a lung infection due to flu, what kinds of signals are the CD8+ T cells receiving in the lungs that are helping them transition to memory T cells? How can we manipulate these mechanisms to form more of these memory cells?”

So far Yeung’s work points to monocytes – a type of immune cell that is recruited to the lungs early on during an infection – as providing the activating signal to allow more CD8+ T cells to become memory cells. Next, she’ll be looking at what happens during a secondary flu infection if 4-1BB signaling is disrupted and there are fewer protective memory T cells.

By deepening the understanding of how immune memory develops, Yeung’s research – which is funded by the Canadian Institutes for Health Research – is laying the groundwork for new approaches that could complement existing flu vaccine strategies to elicit a broader and longer-lasting immune response.

“It takes us closer towards a universal flu vaccine strategy, where one shot will be enough to protect against seasonal influenza and future influenza pandemics as well.”

U of T researcher examines how COVID-19 progressed differently in different parts of Toronto

Christopher.Sorensen — Tue, 18 Apr 2023 13:22:45 +0000

U of T researcher examines how COVID-19 progressed differently in different parts of Toronto

Christopher.Sorensen Tue, 04/18/2023 - 09:22

Cutline

(Photo by Zou Zheng/Xinhua via Getty Images)

Topic

COVID-19

Dalla Lana School of Public Health

Graduate Students

Afia Amoako, a third-year PhD student in the division of epidemiology at the University of Toronto’s Dalla Lana School of Public Health, wants to provide a deeper, more nuanced understanding of how people living in the city experienced COVID-19.

“I’ve always been interested in public health research that focused on the people, rather than the numbers,” says Amoako, adding that she is keen to examine the unequal landscape of the COVID-19 pandemic in Toronto.

Afia Amoako (supplied image)

A recipient of the inaugural Emerging and Pandemic Infections Consortium (EPIC) Doctoral Awards, Amoako’s doctoral research aims to combine spatial and mathematical modelling methods with contact tracing, laboratory testing and census data to paint a fulsome and dynamic picture of COVID-19 in Canada's largest city.

“In Canada, we have very good administrative data and good contact tracing information, but we don’t really have good race-based data,” Amoako says. “The goal of my thesis is to try and put together as much data as I can from different sources to add the ‘people’ element to how we understand the pandemic.”

Her research – which she is pursuing with Dalla Lana School of Public Health Professor David Fisman – focuses on the first two years of the pandemic when access to PCR testing was more widely available. To capture the missing details about the people affected by COVID-19, Amoako is using data from the 2021 census and the Ontario Marginalization Index (ON-Marg), a tool that combines a wide range of demographic indicators to quantify different dimensions of marginalization, including poverty and housing.

She has already completed the first objective of her thesis: analyzing what COVID-19 looked like over space and time during the first four waves of the pandemic.

“Early on in the pandemic, most of the COVID-19 cases were towards the edges of the city, which tend to be lower-income areas,” says Amoako, who studied immunology as an undergradute student at U of T before heading to McGill University to pursue a master’s in public health. ”Then, as the pandemic progressed, particularly with the Omicron wave, the cases really started to centre downtown. That was very interesting to see.”

Next, she will incorporate the sociodemographic data from the census and ON-Marg into her analyses and develop a mathematical modelling approach to understand how the pandemic progressed differently in different parts of the city.

Amoako hopes her research will lay a foundation for how research on infectious diseases can and should adopt a person-centred approach.

“We cannot do research on infectious diseases without talking about the diversity of people who are being impacted. There has to be a discussion about people’s diverse experiences – that is what I really want to achieve through my work.”

Lessons learned during Ebola crisis can help manage Marburg outbreak: U of T expert

Christopher.Sorensen — Thu, 23 Mar 2023 15:08:31 +0000

Lessons learned during Ebola crisis can help manage Marburg outbreak: U of T expert

Christopher.Sorensen Thu, 03/23/2023 - 11:08

Cutline

A colourized transmission electron micrograph of two Marburg Virus particles (image courtesy of NIAID)

Topic

EPIC

World Health Organization

Public Health

Earlier this year, Equatorial Guinea declared its first outbreak of Marburg virus disease, with 11 confirmed deaths so far.

The Marburg virus – a rare but severe hemorrhagic fever which affects both people and non-human primates – belongs to the same family of viruses as Ebola. The disease presents with similar symptoms, including high fever, diarrhea, abdominal pain and cramping, and occasionally severe bleeding.

Rob Fowler, a critical care physician at Sunnybrook Health Sciences Centre and a professor in the department of medicine at the Temerty Faculty of Medicine at the University of Toronto, volunteered with the World Health Organization (WHO) on the frontlines of the Ebola outbreak in West Africa in 2014 and in Congo in 2018. In 2021, he co-chaired the WHO guideline development group that published the first guidelines for Ebola virus disease therapeutics.

He recently spoke with writer Betty Zou at the U of T-based Emerging and Pandemic Infections Consortium (EPIC) about the recent Marburg outbreak and what lessons health professionals can learn from the prior Ebola crisis to help manage this infectious disease.

What do we know about Marburg virus and how it’s transmitted?

Marburg is typically spread from an animal reservoir to other animals or to humans. When it gets into humans, there can be human-to-human spread through direct contact. The direct contact is often through bodily secretions, such as someone vomiting, having diarrhea or bleeding.

Once the virus gets onto a person’s hands, it can enter the body through mucus membranes like your eyes or the inside of your nose and mouth. In rare instances, we’ve seen health-care workers get infected through a needle-stick or sharps injury in the skin that allows the virus to directly enter the blood. And very, very rarely, people have found residual virus in certain bodily fluids that evade the immune response after the acute infectious phase has passed.

How did you react when you first found out that the cluster of people who died of suspected hemorrhagic fever had tested positive for Marburg virus?

Any time there’s a Marburg outbreak, it’s worrisome. Historically, it’s a virus that spreads efficiently from person to person and the mortality has typically been very high.

Like Ebola, this virus often shows up in areas that have underdeveloped health-care systems and a lot of characteristics within society at large that enable person-to-person spread. Tight living quarters is one example. These areas oftentimes don’t have the ability to limit virus spread because of a lack of access to consistent running water. So Marburg or Ebola outbreaks are, of course, very tough for patients and health-care teams, but also very difficult for the health-care system and the population at large to manage.

I feel for the folks that are in the thick of it right now because it’s very, very hard.

What lessons can we take away from the Ebola outbreaks over the past decade to respond to the Marburg virus disease outbreak?

When you have a disease that has a high mortality rate – mortality for Marburg virus disease can range from 25 per cent to 90 per cent – and is very transmissible, we really need to focus on prevention and trying to stop the outbreak from getting larger.

If you’re not living in an area where clinicians are able to send samples for rapid testing, then you can get behind very quickly in an outbreak. Having reference testing laboratories that are geographically nearby is critical. It’s also really important to have a culture of infection prevention and control embedded in health-care settings. The same precautions we use to prevent norovirus transmission in Canada would work well to protect people from more serious viruses like Marburg and Ebola.

If we can provide health-care teams with basic precautionary tools – gloves, gowns, eye protection, medical masks, access to running water and soap – combined with well-practiced infection prevention and control hospital processes, then that will help to prevent spread within health-care facilities.

Another key element is clear and effective messaging to the public about how we can prevent spread in the community. In addition to excellent infection prevention and control practices in hospital, you also need equal engagement in the community where the virus can otherwise spread.

Rob Fowler, second from right, with WHO colleagues, clockwise from bottom left: Sharmistha Mishra, Benon Tumwebaze, Senyonga Muzafalu, Adrienne Chan, Peter Kiiza and Mekonnen Tadesse at the Ebola Clinical Training Centre in Freetown, Sierra Leone (photo courtesy of Rob Fowler)

Where are we with vaccines and treatments for Marburg virus disease?

There currently isn’t an approved vaccine for Marburg virus. However, there are a number of promising early-phase evaluations underway. Having an effective and accessible vaccine is key in terms of prevention of infection.

For treatments, there are nonspecific antiviral medications that may be effective – including repurposed medications such as remdesivir, which has been used to treat people with COVID-19 and tested previously in Ebola virus outbreaks.

Important products in development include monoclonal and polyclonal antibodies that are specific to the Marburg virus. In our experience with Ebola, those antibody treatments were incredibly effective in reducing mortality. For Marburg, that probably represents one of the brightest hopes. To develop these antibodies, there has to be a will – not just medical or societal will, but an economic will – to do it. For Ebola, that economic will existed during and after the 2014 outbreak in West Africa. For Marburg, there has been less of an economic imperative for companies to dive into this, but hopefully that changes.

One of the things that the WHO can do is bring people together from academia, industry and other sectors and set priorities that help to send a signal and direct funds. That has happened recently for Marburg and now there are more candidate drugs being tested. I think there’s lots of hope that, as with Ebola, Marburg will have effective therapies.

What’s your outlook on this current outbreak?

It’s hard to share predictions being so far away from what’s happening on the ground, but I think it’s fair to say that we’re never out of a danger zone when an outbreak is ongoing. Sometimes you have an initial surge of cases being diagnosed, followed by concern among the public and people not seeking care or not getting tested out of fear. That can create a lull between the first set cases and the next bump in cases. The incubation period is usually about a week, but can be up to about three weeks.

Theoretically, if you go three weeks without a new case, you might think that the outbreak is clearing. However, that assumes you know about all the new cases – which is almost never true. There’s a relatively large risk that there will be unknown cases. That’s why we generally go through at least two 21-day periods without a new case before we think an outbreak is over.

How can the EPIC community help respond to outbreaks like this one – now and in the future?

There’s so much expertise in the EPIC community – and in the Toronto and Canadian communities more broadly. I think we really have had an outsized influence on vaccine and therapeutic development, diagnostic testing and clinical care.

Canada has been a leader in developing vaccines and monoclonal antibody treatments that were very helpful during the 2014 Ebola outbreak in West Africa. Supporting lab-based diagnostic capacity in Africa was also incredibly helpful. The National Microbiology Lab in Winnipeg has been very good at supporting other countries and helping them build up their diagnostic capacity.

Canadians have helped to build the foundations of excellent acute and critical care for patients with Ebola – this goes such a long way to reduce mortality even when there isn’t a specific therapy available. Yet, all of this requires people to say that it’s not just someone else’s issue – it’s our collective issue that we can bring our expertise and resources to help with. It’s about individual people asking themselves the question, “Do I have something to offer?” The answer is almost always, “Yes.”

U of T home to new hub that will strengthen Canada’s pandemic preparedness and increase biomanufacturing capacity

Christopher.Sorensen — Thu, 02 Mar 2023 15:42:11 +0000

U of T home to new hub that will strengthen Canada’s pandemic preparedness and increase biomanufacturing capacity

Christopher.Sorensen Thu, 03/02/2023 - 10:42

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(photo by Jonathan Nackstrand/AFP/Getty Images)

Topic

Bioinnovation

Leah Cowen

Sunnybrook Health Sciences

Hospital for Sick Children

Unity Health

Health