From COVID-19 to the seasonal flu and RSV, vaccinations for respiratory viruses are typically delivered via intramuscular injection, which generates antibodies in the bloodstream.
But the first line of defence against these viruses is actually the upper airway, where mucosal antibodies known as immunoglobin A (IGA) can stop pathogens before they even enter the body.
Harnessing IgA responses to provide this sterilizing immunity remains an unmet goal in vaccine development - one that University of Toronto scientists, with the support of Moderna Canada, are laying the groundwork for through fundamental research.
"We want to look at how an IgA response is generated because we don't know too much about how that works at mucosal surfaces," said Natalie Edner, a postdoctoral researcher in the lab of Jennifer Gommerman, a professor and chair of immunology in U of T's Temerty Faculty of Medicine whose team is carrying out research at the forefront of harnessing mucosal immunity to counter respiratory infectious diseases.
Edner is one of two U of T researchers to receive Moderna Global Fellowships, which support emerging researchers whose work can improve preparedness and treatment against various diseases.
A second fellowship will support Rick Lu, postdoctoral researcher in the lab of Bowen Li, an assistant professor in the Leslie Dan Faculty of Pharmacy whose research group has world-leading expertise in the use of lipid nanoparticles (LNPs) to deliver mRNA medicines.
Lu is developing a way to modify immune cells by delivering precise instructions using LNPs, instead of viral vectors, that could result in safer and more scalable cancer treatments.
In addition to the fellowships, Moderna is also supporting research into the use of AI and quantum computing to accelerate the design of mRNA medicines.
The project - part of a framework agreement between U of T and Moderna that was established in 2022 - is taking place in the Matter Lab led by Alán Aspuru-Guzik, a professor of computer science and chemistry in the Faculty of Arts & Science and a leader in the application of AI and quantum computing in health-care and development of next-generation therapeutics.
"This collaboration exemplifies how universities and industry can work together to accelerate innovation," said Leah Cowen, U of T's vice-president, research and innovation, and strategic initiatives. "By supporting next-generation researchers and leveraging cutting-edge technologies, we're building the foundation for breakthroughs that will benefit Canadians and people around the world - from harnessing AI to accelerate mRNA design to developing vaccines that stop infections at the door."
"Canada is home to some of the most innovative scientific minds in the world, and our partnership with the University of Toronto reflects Moderna's long-term commitment to advancing mRNA science through local research excellence," said Rahbar Rahimpour, director of R&D Strategic Alliances at Moderna Canada. "Together, we're not only supporting the next generation of researchers but also building an mRNA centre of excellence to help fuel scientific breakthroughs that will benefit Canadians and global health alike."
The Matter Lab project is being led by postdoctoral researcher Mohammad Ghazivakili. In addition to improving the efficacy of mRNA vaccines, the research team is exploring the use of quantum-driven algorithms to tackle structural complexities around mRNA to shorten the timeline for the design of new vaccines and therapeutics and make them cheaper to produce.
Yet, while technology can speed up design, understanding immune biology remains equally critical. That's why, for years, the Gommerman lab has studied the role of IgA antibodies in mucosal immunity, with a recent paper published in the journal Cell shedding new light into IgA responses in the gut.
"With the Moderna Global Fellowship, Natalie [Edner] will look to understand whether those same rules apply to the airways - to SARS-CoV-2 infection in the upper respiratory tract, or flu infection in the lungs," said Gommerman, who is co-director of the Hub for Health Intelligence & Innovation in Infectious Disease at Temerty Medicine. "As we learn more about how sterilizing IgA is generated in the first place, we can then potentially engineer vaccines to take advantage of those natural pathways that we learn about."
Edner and collaborators in the Gommerman lab will present their research to Moderna's team as the work progresses, providing them with an opportunity to connect with and learn from industry scientists, Edner said.
"It's really helpful to get an idea of how people who work in industry think about these things," she said. "At the end of the day, we want to get better vaccines on the market, so they can help us to understand what's required to actually make that happen."
