A phase 2 trial to evaluate safety and immunogenicity of a next-generation COVID-19 vaccine delivered by inhaled aerosol to humans

Despite the benefit of current COVID vaccines in preventing severe disease and death, these vaccines are relatively poor at preventing infection with new variants like Omicron and work less well in the elderly and people with weak immune systems. There is an urgent need to develop new, next generation vaccines. As leaders in respiratory mucosal immunity, we have shown how delivering a vaccine directly to the lung by inhalation leads to better protection from infection than an IM injection. Before COVID, we were studying a new viral-vectored vaccine for TB inhaled into the lungs in healthy volunteers. We showed that this vaccine was safe and that good immune responses to TB were made in the lungs. With the arrival of COVID, we developed next generation multivalent COVID-19 vaccines active against not only the spike protein but also internal viral proteins that do not mutate, even in variants. After showing that these vaccines were safe and protected against COVID infection in animals, we began a human trial with 30 healthy persons who had at least 2 doses of a mRNA vaccine and are studying in detail the immune responses in the lung and blood. In our planned placebo-controlled Phase 2 study, we will enroll 500 participants from at least 3 clinical trial sites across Canada, to get more confidence in the safety of the inhaled route of administration and make the results more generalizable by enrolling older persons and those with underlying health conditions. We will gather safety and measures of immune responses to support a phase 3 clinical trial, with the goal of licensing and marketing our made-in-Canada vaccine and the aerosol method of administration. We expect this vaccine approach to be effective in breaking the cycle of new variant, poor vaccine performance, transmission and infection. The research team is led by Dr Fiona Smaill and includes members with a rich experience in vaccine clinical trials, vaccine manufacturing, aerosol delivery, and immunology.