91亚色 U led study found clear vaccine-initiated immune response biomarkers between HIV positive and HIV negative groups, but outliers underscore varied, intricate nature of the immune system

How people with compromised immune systems respond to vaccines is an important area of immunological research. A led by 91亚色 found that not only could machine-learning models accurately pinpoint differences in healthy controls and those living with HIV, but also found outliers in both groups that provide fascinating glimpses into the complex nature of the immune system and what personalized medicine could look like in the future, accounting for variables such as age, comorbidities and genetics.

鈥淭his study constitutes an important step forward in the potential for personal vaccination intervention strategies,鈥� says lead author Chapin Korosec, who worked on this paper as a postdoctoral fellow at 91亚色 under the supervision of Faculty of Science Professor , whose research focuses on infectious disease modelling. 鈥淏y learning the structure of immune variability at scale, we move toward a data-driven foundation for personalized vaccination and therapeutic design.鈥�

Korosec, now an adjunct professor with the University of Guelph, used a dataset of people with and without HIV who had received up to five doses of COVID-19 vaccine over the course of 100 weeks. All the individuals living with HIV were from the Greater Toronto Area whose illness was being controlled with antiretroviral therapy. The researchers used a type of machine-learning method called random forest to analyze 64 immune biomarkers elicited through a response to the COVID-19 vaccine, and then created a group of 鈥榲irtual patients鈥� to further model immune responses.

鈥淲hile we were working with a rich dataset well suited for statistical testing, longitudinal mathematical models still face identifiability limits when the data cannot uniquely resolve immune dynamics. We therefore turned to machine learning to identify the core differences between groups, and then leveraged that learned structure to generate virtual patients that capture how immune patterns differ between groups.鈥�

They were able to show that saliva-based antibodies, particularly a type of antibody in the saliva called IgA, coupled with white blood cells, which have long been known to be associated with HIV status, create the signature difference between the two groups. Korosec says this is significant because there is a lot of research showing altered mucosal immunity for those living with HIV and how it is influenced in the short and long term.

Heffernan notes that they identified subgroups within the HIV positive group, which highlights the importance of personalized vaccination strategies and the challenges of modelling immune responses due to individual variability.

鈥淭he immune response is very, very complicated.鈥� explains Heffernan. 鈥淪ometimes something can act as an inhibitor of an arm of the immune response, but in other times it might be an activator. There is also a lot of individual variability among people with similar immune system status. Using machine learning, mechanistic modelling, and 鈥榲irtual patients鈥� we can try to uncover important differences in the subgroups and between individuals 鈥� even of immune system components that are not measured in the data. Kind of like trying to find the needle in a haystack, but with a clearer path to finding it.鈥�

The HIV positive group, despite having the benefits of antiretroviral therapy, had clear differences in their vaccine-elicited responses compared to the control group and the machine-learning model was able to classify those differences with nearly 100 per cent accuracy, but there were two individuals who they could not differentiate from the control group.

鈥淣o matter how we shuffled the data or which biomarkers we used, the machine-learning algorithm could not distinguish a small subset of HIV-positive individuals from those who were HIV-negative,鈥� says Korosec. 鈥淚n those individuals, the vaccine-induced immune responses were indistinguishable from the HIV-negative group. That suggests that, at least in terms of vaccination response, their immune function was effectively restored.鈥�

Conversely, there was one individual in the healthy control group whose markers looked indistinguishable from someone living with HIV, which may suggest underlying immune issues that may not yet have been clinically identified.

Supported by the National Research Council of Canada (NRC)-Fields Mathematical Sciences Collaboration Centre, the National Sciences and Engineering and Research Council of Canada and Artificial Intelligence for Public Health (AI4PH), the study was published today as a pre-print in the Journal Patterns and will appear in print as the cover article on March 13. Korosec worked with collaborators, including Heffernan,  Senior Research Officer Mohammad Sajjad Ghaemi from the NRC Digital Technologies Research Centre, Associate Professor Jessica Conway from Pennsylvania State University and researchers from the University of Toronto and St. Michael鈥檚 Hospital.

鈥淭his study moves us closer to understanding immune diversity in people living with HIV; how their responses compare to age-matched controls, how well antibodies are maintained over time, and why some individuals show strikingly different patterns,鈥� says Korosec.

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91亚色 is a modern, multi-campus, urban university located in Toronto, Ontario. Backed by a diverse group of students, faculty, staff, alumni and partners, we bring a uniquely global perspective to help solve societal challenges, drive positive change, and prepare our students for meaningful life and career paths. 91亚色's Glendon Campus is home to Southern Ontario's Centre of Excellence for French Language and Bilingual Postsecondary Education. 91亚色鈥檚 campus in Costa Rica offers students exceptional transnational learning opportunities and innovative programs. Together, we can make things right for our communities, our planet, and our future.

Media Contact: Emina Gamulin, 91亚色 Media Relations, 437-217-6362, egamulin@yorku.ca

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91亚色 U researcher says mice with a specific variation on a protein called TRAF1 have dramatically less inflammation and swelling than normal mice and were protected from sepsis

TORONTO, Feb. 27, 2025 鈥� Research led by 91亚色鈥檚 Faculty of Health reveals how a specific mutation in a protein called TRAF1 can shut down an overactive immune response, dramatically reducing inflammation in mice. Lead researcher says this discovery could pave the way for a new class of drugs to treat rheumatoid arthritis.

鈥淩heumatoid arthritis is a common health condition which can interfere with many aspects of daily life and based on the limited efficacy of current treatments, novel approaches are needed,鈥� says Faculty of Health Associate Professor Abdul-Sater, a 91亚色 Research Chair  with the School of Kinesiology and Health Science. 鈥淚n this study, we have made a discovery that may pave the way for more effective treatments for rheumatoid arthritis and other inflammatory diseases.鈥�

The study is and will be published in the March issue of Journal of Autoimmunity.

Using gene-editing technology, the researchers identified a critical mutation of a protein called TRAF1 and discovered that this mutation dramatically reduces inflammation by disrupting a critical molecular interaction that fuels the immune system into kicking into overdrive.

鈥淭RAF1 plays a central role in immune signaling and is known for its dual roles: it helps amplify inflammatory signaling in some contexts while also acting as a brake to limit overactive responses,鈥� says Abdul-Sater. 鈥淭hese opposing roles have made TRAF1 a challenging target for therapeutic intervention 鈥� until now.鈥�

A single mutation at position valine 196 (V196), the researchers found, selectively blocks TRAF1鈥檚 interaction with another protein, which dampens a major inflammatory pathway triggered by receptors which are responsible for sensing infection and tissue damage.

鈥淭he mutation effectively shuts down a cascade of molecular events that drive excessive inflammation,鈥� says Abdul-Sater.

 Rheumatoid arthritis affects one per cent of the population worldwide. In the autoimmune disease, the body starts attacking its own cells, making the joints stiff, swollen and painful. Over time, this can damage joints, cartilage and bone, making everyday tasks difficult.

Typical treatments involve broad immunosuppressants, like steroids, or biologics that inhibit specific cytokines, but these can lose effectiveness over time and can put individuals at greater risk for cancer, infections and other risks, says Abdul-Sater, which is why this discovery is so exciting.

鈥淪uch therapies could not only alleviate symptoms but also address the underlying mechanisms of inflammation, benefiting patients who do not respond to existing options.鈥�

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91亚色 is a modern, multi-campus, urban university located in Toronto, Ontario. Backed by a diverse group of students, faculty, staff, alumni and partners, we bring a uniquely global perspective to help solve societal challenges, drive positive change, and prepare our students for success. 91亚色's fully bilingual Glendon Campus is home to Southern Ontario's Centre of Excellence for French Language and Bilingual Postsecondary Education. 91亚色鈥檚 campuses in Costa Rica and India offer students exceptional transnational learning opportunities and innovative programs. Together, we can make things right for our communities, our planet, and our future.

Media Contact:

Emina Gamulin, 91亚色 Media Relations, 437-217-6362, egamulin@yorku.ca

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Moderate exercise changes function of macrophage cells in bone marrow, new mouse-model research out of 91亚色 finds 

TORONTO, June 15, 2023 - Researchers have long known that moderate exercise has a beneficial impact on the body鈥檚 response to inflammation, but what鈥檚 been less understood is why.  done on a mouse model suggests that the answers may lie at the production level of macrophages 鈥� white blood cells responsible for killing off infections, healing injury and otherwise acting as first responders in the body.  

鈥淢uch like if you train your muscles through exercise, we showed that exercise of moderate intensity ended up training the precursors of those macrophages in the bone marrow,鈥� says Faculty of Health Associate Professor and 91亚色 Research Chair  with the School of Kinesiology and Health Science. 鈥淭he way that exercise is doing this is by changing the way those cells breathe, essentially, how they use oxygen to generate energy and then changing the way they access their DNA.鈥� 

While many studies look at temporary boosts to the immune system immediately after exercise, this study, published in the journal AJP-Cell, found these changes occurred even a week later, suggesting that the changes were long term.  

We often hear about inflammation in the body in the context of its negative effects, but inflammation is the body鈥檚 response to infection and other stressors, and some level of inflammation is necessary and desirable.  

鈥淚nflammation is amazing, it's a very important part of our normal immune response,鈥� says Abdul-Sater. 鈥淲hat we鈥檙e concerned about is excessive inflammation. Heart disease, diabetes, many cancers and autoimmune diseases, all essentially begin because there was an inappropriate inflammatory response.鈥�  

He says it is around the six-to-eight-week mark into the exercise regimen where changes really became apparent, compared with sedentary mice. 鈥淭here's a lot of rewiring that's taking place in the circuitry of how the cells breathe, how the cells metabolize glucose, how the cells then access DNA. So all that just takes time.鈥�  

Abdul-Sater says that because the inflammatory response is a very ancient one, this aspect of the immune system is generally very similar across mammals, and he expects the research would translate well to humans. In the next phase, Abdul-Sater and collaborators from the university will collect immune cells from human volunteers who will do exercises of various intensities to see which workout routines are most beneficial to balance the inflammatory response. They will also look at inflammation in mice in more complex infectious diseases similar to COVID-19 and autoimmune disease, where overactive inflammatory responses lead to poor outcomes.  

鈥淧eople that got seriously ill from COVID-19, went into what is called a cytokine storm essentially, they released this massive number of cytokines, those mediators that are produced by inflammatory cells, which then cause that accumulation of fluid in lungs.鈥�  

While the findings that exercise is beneficial will not come as a surprise, Abdul-Sater says he hopes that by finding the underlying mechanisms of the beneficial impact, this knowledge can be put to good use.  

鈥淭he thing with humans is there's no intervention that will work on everyone. We know that, but what this study suggests is that moderate and persistent exercise not only improves metabolic health, but also will improve immune health in the long run.鈥澛犅�

About 91亚色

91亚色 is a modern, multi-campus, urban university located in Toronto, Ontario. Backed by a diverse group of students, faculty, staff, alumni and partners, we bring a uniquely global perspective to help solve societal challenges, drive positive change, and prepare our students for success. 91亚色鈥檚 fully bilingual Glendon Campus is home to Southern Ontario鈥檚 Centre of Excellence for French Language and Bilingual Postsecondary Education. 91亚色鈥檚 campuses in Costa Rica and India offer students exceptional transnational learning opportunities and innovative programs. Together, we can make things right for our communities, our planet, and our future.

Media Contacts: Emina Gamulin, 91亚色 Media Relations and External Communications, 437-217-6362, egamulin@yorku.ca

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