McMaster University researchers have achieved a significant milestone in COVID-19 vaccine development with their inhaled vaccine demonstrating safety and immunogenicity in Phase 1 human trials. The study, which enrolled 36 healthy adults and ran from 2022 to 2024, showed that the vaccine safely generates immune responses associated with protection in the lungs, according to results published in Nature Communications.
Novel Delivery Method Addresses Current Vaccine Limitations
The inhaled vaccine represents a departure from traditional intramuscular injection, delivering the vaccine directly to the lungs as an inhaled mist. This approach provided study participants with three layers of mucosal defense in the respiratory tract, an area where current vaccines offer limited protection.
"Even though they have significantly reduced incidence of death and hospitalization, the current COVID-19 vaccines have generally not provided protection against breakthrough infections," said Fiona Smaill, professor emerita in the Department of Pathology & Molecular Medicine and lead investigator. "Our studies suggest that this is in part due to their inability to provide strong mucosal immunity in the lower respiratory tract — something our inhaled vaccine does quite well."
Strong Foundation for Phase 2 Development
The Phase 1 trial was led by scientists from the Michael G. DeGroote Institute for Infectious Disease Research, including Fiona Smaill, Zhou Xing, Brian Lichty, and Matthew Miller. The successful completion of this initial study has already led to approval for Phase 2 trials, which are currently underway.
"The data generated from these clinical trials position us well to proceed with the next stages of clinical development," said Zhou Xing, a professor in McMaster's Department of Medicine and scientist at the McMaster Immunology Research Centre. "Besides its safety, we have also demonstrated inhaled aerosol delivery of our vaccine to be a powerful way to fill the gap in respiratory mucosal immunity in human lungs."
The Phase 1 trial also helped researchers determine optimal vaccine dosage, which will continue to be evaluated alongside safety and effectiveness parameters during the ongoing Phase 2 trials.
Established Platform with Pandemic Preparedness Potential
McMaster's inhaled vaccine platform was originally established decades ago for tuberculosis research and has now become the flagship translational research initiative at the university's Global Nexus health innovation accelerator. The research team believes this approach could play a crucial role in future pandemic preparedness.
"This trial has made a strong case for inhaled vaccines to become a key tool in the prevention of future outbreaks and pandemics," Smaill noted.
Integrated Research Infrastructure Enables Rapid Development
The success of the program demonstrates the value of McMaster's integrated research infrastructure. Matthew Miller, executive director of Global Nexus and scientific director of the Institute for Infectious Disease Research, emphasized that every aspect of the study was conducted on campus.
"From concept and study design to biomanufacturing and clinical trials, every aspect of this study has been conducted on campus," Miller said. "These inhaled aerosol vaccines not only illustrate a longstanding area of strength for McMaster, but also underscore what the university is truly capable of when we have the right infrastructure and expertise in place."
The university's GMP (good manufacturing practices) biomanufacturing capacity was identified as a key factor in accelerating the pathway to human trials. Brian Lichty, director of McMaster's Robert E. Fitzhenry Vector Laboratory, noted that recent funding from federal and Ontario governments will further enhance this capability.
Commercial Development Through University Spinout
McMaster's inhaled vaccine technology has been licensed to AeroImmune Inc., a university spinout company supported by the McMaster Seed Fund. This commercialization pathway represents part of the university's broader strategy to translate research discoveries into clinical applications.
The trials are supported by McMaster's growing life sciences ecosystem, which includes Global Nexus and the Canadian Pandemic Preparedness Hub, positioning the university to advance additional drugs and diagnostics through clinical development.
