Positive results in animal models have green lit a Phase 1 clinical trial for two inhaled aerosol COVID-19 vaccines developed by scientists at McMaster University in Canada.
As the pandemic (somewhat) transitions to an endemic phase, there is a need for the next generation of SARS-CoV-2 vaccines that can address cases in the short-term beyond the emergency versions created to handle the initial onslaught. In the long run, an effective next-gen vaccine could provide pre-emptive protection against a future pandemic—something not many people were considering before December 2019, but a fact that is now weighing on minds as the world continues to struggle in year two of the COVID-19 pandemic.
Drawing on two decades of research and development on an inhaled tuberculosis vaccine by McMaster’s Zhou Xing, a team of researchers has created a unique solution—an inhaled SARS-CoV-2 vaccine that can resist variants. Two versions of the vaccine are currently in Phase 1 clinical trials after a successful preclinical study on mice showed broad, long-lasting protection against both the original strain of SARS-CoV-2 and variants of concern.
“Our vaccine strategy differs from all of the current first-generation COVID-19 vaccines in the route of delivery,” said Xing. “Besides neutralizing antibodies and T cell immunity, the vaccine delivered into the lungs stimulates a unique form of immunity known as trained innate immunity, which is able to provide very broad protection against many lung pathogens besides SARS-CoV-2.”
In the clinical trial, 30 volunteers who already received two doses of a COVID-19 mRNA vaccine will receive one of two inhaled vaccines. The researchers are comparing two strains of weakened adenovirus as platforms for the vaccines. In their natural form, adenoviruses cause respiratory infections like the common cold, and in rare cases can cause a lung infection, such as pneumonia. But in their weakened form, rather than spread disease, they can be customized to serve as vehicles to trigger targeted immune responses.
Both vaccines express three different SARS-CoV-2 proteins—the well-known spike protein in addition to two others that are highly conserved among coronaviruses and do not mutate as quickly as spike.
“By targeting a breadth of immune responses to different parts of the COVID virus, we expect to see broader protection,” said Fiona Smaill, professor of pathology and molecular medicine at McMaster, and leader of the clinical trial.
During the clinical trials, researchers will examine how the immune response develops in the lungs and blood after vaccination and monitor for possible side effects.
In addition to being needle and pain-free, an inhaled vaccine is so efficient at targeting the lungs and upper airways that it can achieve maximum protection with a small fraction of the dose of current vaccines—possibly as little as 1 percent. In practice, this would mean a single batch of vaccine could go 100 times further.
“This pandemic has shown us that vaccine supply can be a huge challenge,” said Brian Lichty, who co-led the preclinical study. “Demonstrating that this alternative delivery method can significantly extend vaccine supply could be a game changer, particularly in a pandemic setting.”
If the Phase 1 clinical trial is successful, the researchers say they have already manufactured sufficient doses to move forward with a much larger clinical trial.
Photo: Researcher Michael D’Agostino demonstrates use of the nebulizer. Credit: Georgia Kirkos