Vaccines

Institute of Biomedical Engineering

Connaught Fund

Faculty of Applied Science & Engineering

Centre for Vaccine Preventable Diseases

Subheadline

"This work could lay the foundation for more effective vaccines that curb the spread of STIs, particularly in marginalized communities disproportionately affected by these diseases”

A research team from the University of Toronto is creating a new generation of vaccines that aims to overcome key hurdles faced by some existing formulations.

For example, a common shortcoming of many traditional vaccines is that they can’t produce antibodies in tissues where sexually transmitted infections (STIs) often enter the body.

“Most current vaccines fail to produce sufficient antibodies within mucosal tissues, leaving a significant gap in our defense against sexually transmitted infections,” says Aereas Aung, an assistant professor at the Institute of Biomedical Engineering in the Faculty of Applied Science & Engineering who is leading the research effort.

“Our goal is to develop a novel strategy that leverages the strengths of parenteral vaccination while also targeting the mucosal immune system.”

Normally vaccines are injected parenterally, meaning it is injected into or under the skin, into the muscle or directly into the bloodstream. The vaccine then travels to lymph nodes, which are small glands that help produce antibodies. Mucosal tissues in the cervix and rectum present a unique challenge since the mucus in these areas can break down the vaccine quickly and wash it away, making it difficult to reach the lymph nodes and be effective.

Aung’s research proposes fusing a protein carrier to the disease antigens, allowing it to reach distant mucosal lymph nodes after injection.

“We aim to incorporate potent immunostimulatory components into our antigen construct, optimizing its distribution and enhancing mucosal antibody responses,” says Aung.

“If successful, this work could lay the foundation for more effective vaccines that curb the spread of STIs, particularly in marginalized communities disproportionately affected by these diseases.”

Aung’s project is one of 51 U of T faculty members whose work is being supported by the Connaught New Researcher Awards in the most recent round – and one of eight at U of T Engineering. The award helps early-career faculty members establish their research programs.

The other U of T Engineering researchers whose projects are supported by the award are: 

Mohammed Basheer, department of civil and mineral engineering – Integrated hydrological-statistical method and tool for landslide susceptibility mapping in a changing climate
Daniel Franklin, Institute of Biomedical Engineering – Development of equitable pulse oximeters
Sarah Haines, department of civil and mineral engineering – Open Plenums & Indoor Environments (OPEN): Evaluating the impact of return air systems on indoor environmental quality
Mark Jeffrey, Edward S. Rogers Sr. department of electrical and computer engineering – Productively surmounting the memory wall with task parallelism
Caitlin Maikawa, Institute of Biomedical Engineering – Affinity-directed dynamic polymer materials for biomarker sensing
Mohamad Moosavi, department of chemical engineering and applied chemistry – Learning the Language of Metal-Organic Frameworks Topology
Cindy Rottmann, Institute for Studies in Transdisciplinary Engineering Education and Practice (ISTEP) – But I could be fired! How early career engineers hold the public paramount from organizationally subordinate locations

Do you have questions about children's vaccines? A new phone line has the answers

Christopher.Sorensen — Mon, 05 Feb 2024 14:18:11 +0000

Do you have questions about children's vaccines? A new phone line has the answers

Christopher.Sorensen Mon, 02/05/2024 - 09:18

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(photo by SDI Productions/Getty Images)

Ishani Nath

Topic

Our Community

Pediatrics

Hospital for Sick Children

Subheadline

The SickKids Vaccine Consult Service (VCS) aims to answer caregivers’ questions about all pediatric vaccinations

Canada is in the midst of respiratory illness season, yet the number of individuals getting the updated COVID-19 and flu vaccines remains low. The number of children receiving routine vaccinations has also dropped since the pandemic.

For the past few years, questions about vaccines dominated headlines and internet searches. Is this vaccine safe? Will it work? Who needs to get vaccinated?

Shaun Morris, a clinician scientist at The Hospital for Sick Children (SickKids) and an associate professor of pediatrics in the University of Toronto’s Temerty Faculty of Medicine, and Pierre-Philippe Piché-Renaud, who is pursuing a clinical and research fellowship at SickKids and graduate studies at U of T’s Dalla Lana School of Public Health, routinely field these types of questions from parents and caregivers.

Both are members of the Centre for Vaccine Preventable Diseases (CVPD) at the Dalla Lana School of Public Health.

Shaun Morris and Pierre-Philippe Piché-Renaud (supplied images)

To help boost confidence in vaccination through easy access to reliable, evidence-based information, Morris and Piché-Renaud have launched a new pilot project running until the end of March.

The SickKids Vaccine Consult Service (VCS), part of a larger project funded by the Public Health Agency of Canada (PHAC), is offering a phone service staffed by nurses to answer caregivers’ questions about all pediatric vaccinations. The intent is to make vaccine information more accessible and, ultimately, help parents make the best, most informed decision for their child, Piché-Renaud says.

Building on previous success

The pilot project builds off the success of a COVID-19-specific VCS phone line that ran from October 2021 to March 2023. The COVID-19 VCS received more than 2,700 calls from caregivers asking about COVID-19 vaccines for children. The phone line was staffed by health-care professionals who provided information tailored to each individual circumstance, including living situation or medical history – answers that could not typically be found on the internet.

The nurses fielding calls were trained to create an open and safe environment, explains Julia Orkin, the SickKids COVID-19 VCS medical lead and an associate professor in U of T’s department of paediatrics in the Temerty Faculty of Medicine.

“It wasn’t, you know, ‘you must do this,’ it was really a shared supportive conversation,” she says. After calling in, 83 per cent of caregivers surveyed said their questions and concerns were addressed, and more than 60 per cent said they would proceed with vaccination.

The new phone service expands beyond the COVID-19 VCS by fielding questions not only about COVID-19 vaccines but all childhood immunizations. The service is open to anyone in Ontario, with a specific focus on patients with existing medical concerns and equity-deserving populations throughout the Greater Toronto Area.

Insurance coverage and internet access aren’t required to book a VCS consultation and translation services are available.

Piché-Renaud says that the conversations are about “taking it one step at a time, meeting parents where they are, and addressing their concerns.”

Research has shown that COVID-19 vaccine uptake was lower among certain groups – for instance, certain racialized and lower income populations. To reach these communities, Morris and Piché-Renaud are working with organizations like Black Creek Community Health Centre, Taibu Community Health Centre and the Paediatric Alliance of Ontario.

“The messaging is going to come through the people that [caregivers in these communities] already know and work with,” says Piché-Renaud.

Meeting an urgent need

Providing information on the importance of childhood vaccinations is particularly urgent.

“Immunization coverage for a variety of diseases is lagging behind, leaving kids susceptible to infections and outbreaks that are completely preventable. It’s essential to provide parents with clear, individually tailored messaging from a trusted source to enable them to make informed decisions for their children,” says Shelly Bolotin, director of the Centre for Vaccine Preventable Diseases and an associate professor at the Dalla Lana School of Public Health.

During the pandemic, routine childhood immunizations for preventable diseases like meningitis, measles and polio were set back to levels not seen since 2008. The proportion of Canadians who view vaccines as important for children also dropped from 91 to 82 per cent, according to UNICEF’s 2023 State of the World’s Children report. Canada has since seen cases of pertussis (whooping cough) and other vaccine preventable diseases.

“We’re still seeing kids who show up at SickKids and other paediatric hospitals with vaccine preventable illnesses, like certain types of meningitis,” says Piché-Renaud.

The physicians hope that through the VCS phone line and a related project working with SickKids pediatricians and patients, they will be able to better understand why some children are not getting vaccinated. With this information, they can then develop resources such as educational websites, or improve access to vaccination sites.

Making trusted vaccine information more accessible

Morris and Piché-Renaud encourage Ontario parents wondering about childhood vaccines to book a consultation appointment at SickKids VCS.

For Morris, empowering patients and families to make the best health decisions for themselves is one of the most important aspects of his job. Services like the VCS phone line help achieve that goal by “enabling people to connect to trusted sources of information and navigate through the quagmire of not good information, which is probably more common in the realm of immunization than in most areas.”

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

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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)

Betty Zou

Topic

Emerging and Pandemic Infections Consortium

COVID-19

Institutional Strategic Initiatives

Sinai Health

Sunnybrook Health Sciences

Laboratory Medicine and Pathobiology

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.

Researchers discover lipid nanoparticle that delivers mRNA to muscles, avoids other tissues

Christopher.Sorensen — Fri, 15 Dec 2023 20:01:28 +0000

Researchers discover lipid nanoparticle that delivers mRNA to muscles, avoids other tissues

Christopher.Sorensen Fri, 12/15/2023 - 15:01

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“The substantial anti-tumor effects observed with iso-A11B5C1 underscore its promise as a viable candidate for cancer vaccine development,” says Jingan Chen, a PhD trainee from the Institute of Biomedical Engineering (photo by Steve Southon)

Kate Richards

Topic

Institute of Biomedical Engineering

Institutional Strategic Initiatives

PRiME

Cancer

Graduate Students

Leslie Dan Faculty of Pharmacy

Subheadline

Study also showed the mRNA triggered potent cellular-level immune responses, suggesting it could be used to develop a melanoma cancer vaccine

A team of researchers based at the University of Toronto’s Leslie Dan Faculty of Pharmacy have discovered an ionizable lipid nanoparticle that delivers mRNA to muscles while avoiding other tissues.

The study, led by Assistant Professor Bowen Li and published in Proceedings of the National Academy of Sciences, also showed that mRNA delivered using the lipid nanoparticles triggered potent cellular-level immune responses – a proof-of-concept that could lead to a potential melanoma cancer vaccine.

Called iso-A11B5C1, the new lipid nanoparticle demonstrates exceptional mRNA delivery efficiency in muscle tissues while also minimizing unintended mRNA translation in organs such as the liver and spleen. Additionally, study results show that intramuscular administration of mRNA formulated with this nanoparticle caused potent cellular immune responses, even with limited expression observed in lymph nodes.

“Our study showcases for the first time that mRNA lipid nanoparticles can still effectively stimulate a cellular immune response and produce robust anti-tumor effects, even without direct targeting or transfecting lymph nodes,” said Li.

“This finding challenges conventional understandings and suggests that high transfection efficiency in immune cells may not be the only path to developing effective mRNA vaccines for cancer.”

Lipid nanoparticles, also called LNPs, are crucial for delivering mRNA-based therapies including COVID-19 mRNA vaccines that were used worldwide during the recent pandemic. However, many LNP designs can inadvertently result in substantial mRNA expression in off-target tissues and organs like the liver or heart, resulting in often treatable but unwanted side effects. The drive to improve the safety of mRNA therapies that have the potential to treat a broad range of diseases means there is an urgent need for LNPs designed to minimize these off-target effects, explains Li, a recent recipient of the Gairdner Early Career Investigator Award.

From left to right: researchers Jingan Chen, Bowen Li and Yue Xu (photo by Steve Southon)

The new research shows that, compared to the current benchmark LNP developed by the Massachusetts-based biotechnology company Moderna, iso-A11B5C1 demonstrated a high level of muscle-specific mRNA delivery efficiency. It also triggered a different kind of immune response than what is seen in vaccines used to treat infectious diseases.

“Interestingly, iso-A11B5C1 triggered a lower humoral immune response, typically central to current antibody-focused vaccines, but still elicited a comparable cellular immune response. This finding led our team to further explore this as a potential cancer vaccine candidate in a melanoma model, where cellular immunity plays a pivotal role,” Li said.

The interdisciplinary research team that conducted the study includes Jingan Chen, a PhD trainee from the Institute of Biomedical Engineering, and Yue Xu, a postdoctoral researcher in the Li lab and a research fellow associated with PRiME, a U of T institutional strategic initiative.

“Although iso-A11B5C1 showed limited capacity to trigger humoral immunity, it effectively initiated cellular immune responses through intramuscular injection,” said Chen. “The substantial anti-tumor effects observed with iso-A11B5C1 underscore its promise as a viable candidate for cancer vaccine development.”

New platform allows for faster, more precise lipid design

The research team identified iso-A11B5C1 by using an advanced platform developed to quickly create a range of chemically diverse lipids for further testing. This platform, newly introduced as part of the study, overcomes several challenges by streamlining the process of creating ionizable lipids that have a high potential to be translated into therapies.

By rapidly combining three different functional groups, hundreds to thousands of chemically diverse ionizable lipids can be synthesized within 12 hours.

“Here we report a powerful strategy to synthesize ionizable liquids in a one-step chemical reaction,” said Xu. “This new platform provides new insights that could help guide lipid design and evaluation processes going forward and allows the field to tackle challenges in RNA delivery with a new level of speed, precision and insight.”

Researchers partner with Moderna to develop new mRNA-based therapies for HIV and other diseases

siddiq22 — Wed, 26 Jul 2023 19:19:09 +0000

Researchers partner with Moderna to develop new mRNA-based therapies for HIV and other diseases

siddiq22 Wed, 07/26/2023 - 15:19

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(Photo by Amornrat Phuchom/iStock/Getty Images Plus)

Topic

EPIC

Betty Zou & Mayuri Punithan

Subheadline

Projects will develop mRNA vaccines to treat HIV infection and technologies to modulate the body's immune response

Two teams of researchers at the University of Toronto have partnered with Moderna Canada to advance new mRNA-based therapies for HIV and other diseases.

The projects – one led by Mario Ostrowski, an infectious disease physician at Unity Health Toronto and a professor of medicine, immunology and pathobiology and lab medicine at the Temerty Faculty of Medicine; and the other by Haissi Cui, assistant professor in the department of chemistry in the Faculty of Arts & Science, and Landon Edgar, assistant professor in the department of pharmacology and toxicology in the Temerty Faculty of Medicine and an investigator in the PRiME research group – are supported through the partnership framework agreement between U of T and Moderna.

Launched in April 2022, this partnership was the first between Moderna and a Canadian university and provides opportunities for U of T researchers to collaborate with a leading biotechnology firm to create new tools to prevent and treat diseases.

“The partnership between the University of Toronto and Moderna Canada is a testament to the power of industry and academic collaborations, and one that will advance the frontier of mRNA-based vaccines and therapies,” said Derek Newton, assistant vice-president, innovation, partnerships and entrepreneurship at U of T.

“Researchers from both organizations have a shared vision to create new health-care innovations to prevent and treat infectious diseases that will impact patients across Canada and globally.”

From left: Researchers Mario Ostrowski, Haissi Cui and Landon Edgar will be working on projects supported through the partnership framework agreement between U of T and Moderna (supplied photos)

Ostrowski’s project brings together his decades of research on the immune response to HIV with Moderna’s expertise in mRNA vaccines to develop personalized mRNA vaccines to treat HIV infection.

This strategy could address one of the biggest challenges in HIV management: the long-term persistence of viral reservoirs within immune cells in the body, which necessitates life-long antiretroviral therapy treatments for people with HIV. While these therapies help people with HIV live longer, they can also lead to side effects that negatively impact a person’s overall physical and mental health.

To tackle this challenge, the researchers will design mRNA vaccines that are tailored to the unique strain of HIV found in each person. Ostrowski believes that these highly targeted vaccines can activate powerful immune cells to seek out and eliminate hidden viral reservoirs. Similar approaches have been used successfully to create personalized therapeutic vaccines for people with cancer.

This work will also leverage the capabilities of the Toronto High Containment Facility (THCF), which is equipped to allow researchers to study high-risk pathogens, such as HIV and SARS-CoV-2, in a safe and secure way. The facility is a cornerstone of the Emerging and Pandemic Infections Consortium (EPIC) institutional strategic initiative, a partnership between U of T and five major Toronto hospitals to advance innovative infectious disease research and strengthen preparedness for future pandemics.

Containing the only containment level 3 (CL3) research lab in the Greater Toronto Area and the largest in the province, the THCF plays a critical role in supporting Ontario’s life sciences research ecosystem. Its unique infrastructure and capabilities enable cutting-edge research on vaccines and therapeutics and provide training opportunities needed to drive innovation and biomanufacturing in Ontario.

Modulating the body’s immune response is also at the core of the project led by Cui and Edgar.

Their work focuses on the sugars that coat the outside of all immune cells. These sugars, called glycans, have recently been shown to play an important role in fine-tuning the function of some immune system components. However, designing targeted and effective therapies to modulate the glycans themselves has remained elusive.

In collaboration with Moderna, Cui and Edgar will develop mRNA technologies that can be used to adjust glycan levels within specific tissues – or even on specific cell types. If successful, this approach could be used to alter how immune cells function in a myriad of diseases.

Through this cross-faculty and cross-sector collaboration, Cui and Edgar’s work would demonstrate the feasibility of using these cutting-edge technologies to manipulate the architecture of a cell’s surface and to improve immune responses through cell-surface engineering.

“At Moderna, we are focused on the creation of transformative mRNA medicines. For the past 13 years, we have been investing in research and innovation into different facets of mRNA science,” says Patricia Gauthier, Moderna Canada president and general manager.

“Our collaboration with the University of Toronto and its exceptional scientists further strengthens our resolve to push the boundaries of what can be achieved in this rapidly evolving field to improve the lives of patients through mRNA science.”

As part of the partnership, each team will be paired with a scientific expert at Moderna who can champion their research and provide support and feedback.

The selection of these two projects follows the announcement in October 2022 of a partnership between Moderna and a team of U of T researchers led by Omar F. Khan, an assistant professor in the Institute of Biomedical Engineering, to develop next-generation RNA platform technologies. The project recently received support from the Natural Sciences and Engineering Research Council of Canada Alliance Grant program, which aims to foster collaborations between university researchers and partner organizations in the private, public and not-for-profit sectors.

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Institute of Biomedical Engineering

Research aims to help parents prepare for RSV immunizations for children

siddiq22 — Wed, 19 Jul 2023 18:50:09 +0000

Research aims to help parents prepare for RSV immunizations for children

siddiq22 Wed, 07/19/2023 - 14:50

Cutline

(photo by FatCamera/Getty Images)

Ishani Nath

Topic

Centre for Vaccine Preventable Diseases

Pediatrics

Immunology

Two new ways to protect children from respiratory syncytial virus, better known as RSV, may soon be available in Canada – and a University of Toronto researcher aims to ensure parents can make an informed decision about vaccination.

Even though the majority of children will get infected by age 2, “most parents do not know about RSV,” says Tiffany Fitzpatrick, an assistant professor at the Dalla Lana School of Public Health and a member of the Centre for Vaccine-Preventable Diseases.

She’s heard from parents who only learned about the virus – which has a similar seasonal pattern to the flu and symptoms such as coughing, wheezing, and fever – after their child caught it. Although most cases are mild, RSV can lead to more severe illness like pneumonia, and is the leading cause of infant hospitalization in Canada and many other countries.

Tiffany Fitzpatrick (supplied image)

Health Canada is in the process of approving more immunization options to protect children against RSV – an antibody-based drug that may eventually be used to protect all newborns from severe RSV illness and a vaccine for pregnant people that would pass protection from parent to newborn. The potential impact of these new options, both for the health of Canadians and an already overburdened health-care system, is massive.

“This could be really revolutionary,” says Fitzpatrick, who is also a scientist at Public Health Ontario.

That is, as long as parents have the information necessary to make an informed decision about vaccination and understand the severity of RSV – a task that Fitzpatrick plans to address with her research, recently funded by the Canadian Immunization Research Network.

New RSV immunization options coming to Canada

The new RSV prevention drug and vaccine have been a long time coming. Despite more than 60 years of research, options for protecting vulnerable populations (such as newborns) against the virus remained limited – until now.

Currently, the only option for protecting newborns at the highest risk of hospitalization (those born very prematurely, born with heart or lung conditions, or those born in remote communities without quick access to medical care) is a monoclonal antibody therapy called palivizumab. The drug cannot treat RSV, but if injected every month during RSV season, it can help prevent severe illness.

However, palivizumab comes with a high price tag and needs to be administered every month – sometimes for up to six months – so it is typically reserved for high-risk infants. Health Canada recently approved a longer-acting antibody-based drug, nirsevimab, which would only require one injection per RSV season. Nirsevimab is expected to cost much less than palivizumab, and it may eventually be an option for all parents.

A vaccine for pregnant people to help protect newborns from infection is also in the pipeline and may be approved as soon as later this year. The vaccine, recently approved in the U.S. for older adults, offers the prospect of protection against RSV infection – not just disease – to all newborns for the first time.

This RSV vaccine, made by Pfizer and known as RSVpreF, would be given to individuals in their late second or third trimester of pregnancy. The vaccine prompts the pregnant person to makes antibodies that are transferred to their fetus, so their child is born with some protection against RSV. In a worldwide, double-blind clinical trial with pregnant women published in The New England Journal of Medicine, the RSVpreF vaccine was more than 81 per cent effective at protecting infants against serious health issues caused by RSV, like lower respiratory tract illness.

Health Canada is on the verge of approving a new drug and a vaccine to protect children from respiratory syncytial virus (RSV), shown here in an electron micrograph image (image by NIAID)

Speaking with parents about RSV and vaccination

In advance of the rollout of nirsevimab and Health Canada’s consideration of RSVpreF data, Fitzpatrick is listening to parents and learning about their understanding of RSV and potential concerns. Her research will involve conducting interviews with parents across Canada and using the information to create tailored educational materials that address questions and provide the information parents may need as they consider their future RSV immunization options.

“We need to start planning now to make sure that parents are anticipating this, and they have the information they need to be able to make that decision,” she says.

In addition to surveys and interviews, Fitzpatrick and her collaborators will be engaging with populations more vulnerable to RSV. For instance, research indicates that certain living conditions can play a role in a child’s risk for RSV.

“We know if a child is exposed to mould, or if they live in a crowded house, they’re much more likely to catch any respiratory virus and for it to become a much more severe disease,” Fitzpatrick says.

Specific regions and demographics are also disproportionately impacted by RSV. Collaborators on Fitzpatrick’s study will focus on parents in Nunavut – an area that has the highest rates of RSV hospitalization in the world.

“They’re going to be working with community partners there to understand the unique barriers and motivators for RSV immunization in Inuit communities,” she says.

Fitzpatrick is aiming to have the educational materials from her study available in time for next year’s RSV season, when nirsevimab and vaccines for pregnant people will hopefully both be available.

“I hope this research provides parents with the information that they need to make the decision that’s right for them,” she says, noting that as a public-health practitioner, she ultimately hopes people decide to get immunized “so we can prevent as much RSV disease as possible.”

Derrick Rossi, the stem cell scientist who co-founded Moderna, receives honorary degree

Christopher.Sorensen — Fri, 09 Jun 2023 20:04:37 +0000

Derrick Rossi, the stem cell scientist who co-founded Moderna, receives honorary degree Christopher.Sorensen Fri, 06/09/2023 - 16:04

Topic

Factor-Inwentash Faculty of Social Work

Honorary Degree

A stem cell scientist and successful biotechnology entrepreneur, Derrick Rossi knew he was onto something big in 2009, when his Harvard University lab was able to successfully modify messenger RNA – molecules that relay genetic information in the body.

He immediately recognized the potential to develop new treatments for disease and co-founded the biotechnology firm Moderna – the name a play on “modified mRNA.”

What the University of Toronto alumnus couldn’t anticipate at the time was the arrival, a decade later, of COVID-19 – and the role Moderna would ultimately play in developing a vaccine that would save countless millions of lives.

“That was not foreseen,” he told U of T News in 2021.

Today, for his ground-breaking scientific research that has been translated into effective therapeutics with global impact, and for his extraordinary contributions to global public health and biotechnology innovation, Rossi will receive a Doctor of Laws, honoris causa, from the University of Toronto.

Rossi was born in Toronto, the youngest of five children to Maltese immigrant parents. He attended Dr. Norman Bethune High School in Scarborough, where he says a science class instilled in him a passion for molecular biology. “As soon as I learned about molecular biology that was it, I knew what I wanted to be,” he told the National Post in 2020.

He went on to earn two degrees in molecular genetics at U of T, then a PhD from the University of Helsinki. He did a post-doc at Stanford University, and in 2007 was appointed assistant professor at Harvard University, where he ran his own lab.

From left: Dalla Lana School of Public Health Dean Adalsteinn Brown, Derrick Rossi, Chancellor Rose Patten and President Meric Gertler (photo by Lisa Sakulensky)

Rossi’s research focused on stem cells. In particular, he was interested in determining whether he could modify the messenger RNA molecules to relay genetic code to human cells. “Genes and mutations in genes underlie pretty much all human genetic diseases, which is a large fraction of human diseases,” Rossi said in the interview with U of T News.

He realized that if you could “reprogram” a cell to bypass bad genes and mutations, then you could, in theory, treat a large range of genetic disorders, from Parkinson’s disease to sickle cell anemia and more.

Rossi initially didn’t expect the discovery to serve as a platform for a new kind of vaccine. The reason was financial, not scientific: vaccines are generally not very profitable. “It’s not something that a biotech company would be thinking about because there’s not much money to be made there,” he told U of T News.

The exception, it turns out, is a global pandemic.

Having undergone a career transition in 2010 from scientist to scientist-entrepreneur, Rossi says his research became increasingly focused on real-world applications. “As a biologist in a lab, you can answer a question that’s really interesting but isn’t going to move the needle on patient health at all,” he told U of T News. “Or you can ask a different question that, if you get an answer to it, might solve a [patient’s] problem.

“As soon as I realized that, pretty much all the questions we asked in my lab had that type of focus.”

He notes that co-founding Moderna gave him the entrepreneurial “bug.” Since leaving the company in 2014 (he is still an investor), he has co-founded four other biotech startups: Intellia Therapeutics, which uses the genome editing technology CRISPR/Cas9 to create novel medicines for genetic diseases; Magenta Therapeutics, which is developing ways to use stem cell transplants to reset patients’ immune systems to cure autoimmune and other diseases; Stelexis Therapeutics, which focuses on the discovery of drug targets for cancerous stem cells: and Convalo Therapeutics, which has identified promising drug targets for treating neurological disorders.

Rossi, who retired from Harvard in 2018, is a recipient of the Princess of Asturias Award for scientific research – an honour previously conferred on Stephen Hawking and AI pioneer and U of T University Professor Emeritus Geoffrey Hinton. He serves as a mentor at the Rotman School of Management’s Creative Destruction Lab and conducts many media interviews in an effort to expand public knowledge about vaccine efficacy and safety. In 2011, Time magazine named Rossi one of the world’s 100 most influential people.

In his convocation address today to graduate students in social work and public health, Rossi urges them to choose the road less travelled. “And if there isn’t a road there? That’s even better. Grab a machete and whack your way through the jungle of life, forging your own path. By doing so, you will maximize your life experience by colouring it in hues and pigments that you didn’t even know existed ... this is also a great strategy to prepare oneself for whatever may come your way in the future.”

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

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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)

Betty Zou

Topic

Emerging and Pandemic Infections Consortium

EPIC

Leslie Dan Faculty of Pharmacy

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.”

With $3-million chair, U of T and GSK focus on enhancing pharmacist-led vaccine care

Christopher.Sorensen — Wed, 10 May 2023 16:57:15 +0000

With $3-million chair, U of T and GSK focus on enhancing pharmacist-led vaccine care

Christopher.Sorensen Wed, 05/10/2023 - 12:57

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(photo by Prostock Studio)

Kate Richards

Topic

Our Community

The University of Toronto and biopharma company, GSK are investing a combined $3 million – $2 million from GSK and $1 million from the Leslie Dan Faculty of Pharmacy – to create a new chair that will enhance and develop vaccine education programs and practice tools for pharmacists and other health professionals.

Based at the Leslie Dan Faculty of Pharmacy, the GSK Chair in Vaccine Education and Practice-Oriented Tools will build on current knowledge and training to equip pharmacists with the skills and tools to adapt to the rapidly evolving clinical scope of practice and the needs of patients and communities.

The chair will also develop evidence-based models of vaccine care that build trust, expand access and improve health outcomes.

“Community pharmacies are increasingly seen as health hubs for primary-care services and pharmacists are ideally suited to promote the best health outcomes for vaccine-preventable diseases at all stages, from childhood to older adults,” said Lisa Dolovich, professor and dean at U of T’s Leslie Dan Faculty of Pharmacy. “The support from GSK to establish this chair is vital to advancing our education and research in this important area of practice.”

From left to right: Dr. Bryan Tennant, scientific director, vaccines, GSK Canada; Marni Freeman, vice-president and country medical director, GSK Canada; Peter Fonyodi, business unit head, vaccines, GSK Canada; Jamie Kellar, associate dean, academic, Leslie Dan Faculty of Pharmacy; Emanuela De Franco, national director partnerships and governmental affairs, GSK Canada; and Lisa Dolovich, professor and dean, Leslie Dan Faculty of Pharmacy.

As one of the most accessible primary-care providers, pharmacists engage in health promotion, identify indications for vaccines, provide education to patients, administer vaccines and deliver follow-up care.

“At GSK, we believe strong collaborations, such as this one with U of T, are key to driving innovation and excellence in research and education with the goal of improving patient experiences and health outcomes,” said Dr. Bryan Tennant, scientific director, vaccines, at GSK Canada. “We believe that the Leslie Dan Faculty of Pharmacy and the new GSK Chair in Vaccine Education and Practice-Oriented Tools will lead the way in equipping the next generation of pharmacists for an always evolving world and set new standards in education across Canada and around the globe.”

During the mass rollout of COVID-19 vaccines, pharmacy teams across Canada demonstrated the ability to mobilize to meet public health needs in times of crisis. As the impact of the pandemic continues to stretch our health system, pharmacists are taking on an increased role in primary care, filling care gaps with pharmacy clinic services that include vaccinations. “But we need to ensure pharmacists are continually supported with evidenced-based tools to provide the best possible care over time,” Dolovich said.

As a result of limited access and other barriers brought on during the height of the pandemic, many children and adults are behind on routine immunizations.

A 2022 survey led by Campaign Research showed that one in five Ontario adults missed or delayed their routine immunization for preventable illnesses like shingles and pneumonia. Pharmacy teams can help address gaps in care like this and have demonstrated the ability to be nimble enough to implement new, innovative ways of providing critical health services.

“Further supporting and enhancing the role of pharmacists as vaccine-care providers expands access for patients and helps support the health of our families and communities,” said Dolovich. “The creation of this chair provides an exciting opportunity to focus on how pharmacists can continue to play an important role in managing vaccine-preventable diseases.”

The Leslie Dan Faculty of Pharmacy will soon begin recruitment for the chair through an open call for applications and submissions outlining proposed research programs that will drive the vision and impact of this initiative forward.

Flu, COVID-19 and more: Leslie Dan Faculty of Pharmacy expert on the importance of getting vaccinated

Christopher.Sorensen — Mon, 21 Nov 2022 16:12:21 +0000

Flu, COVID-19 and more: Leslie Dan Faculty of Pharmacy expert on the importance of getting vaccinated

Christopher.Sorensen Mon, 11/21/2022 - 11:12

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U of T Vice-President and Provost Cheryl Regehr receives a vaccination at the Discovery Pharmacy on the St. George campus (photo by Johnny Guatto)

Mariam Matti

Topic

Our Community

COVID-19