Ruminations: Inhailng a COVID-19 Vaccine

"[The original idea early in the vaccine race, was to offer it as a standalone], but as time has gone on, virtually everybody has now had the opportunity to get an mRNA vaccine."
"[The McMaster formula is administered through a jet nebulizer that generates a fine misty solution] with particles that are so tiny they're breathed right down deep into the lung."
"If you can generate that local immune response in the lung [it may prove better to boost with an inhaled vaccine]. For a number of reasons this has the promise of being a more effective way to boost [the immune system against COVID-19]."
"We seem to be doing better this time around, than we were a year ago. We've got vaccines. We've got an understanding of what the major risks are in terms of transmission. So we've made progress. How do we keep on without ever going back?"
"I think that's really what I'm looking for."
Fiona Smaill, professor of pathology and molecular medicine, McMaster University, Hamilton

Fiona Smaill and research coordinator Emilio Aguirre demonstrate the use of the nebulizer with a volunteer. Photo by Georgia Kirkos

An inhaled COVID-19 vaccine in humans is to begin the testing process by Canadian scientists, with the goal of targeting both the mutating spike protein that the SARS-CoV-2 virus uses to sneak into human cells, but as well two other targets not as susceptible to mutating. This will not be a vaccine to be injected into the deltoid muscle in the upper arm, but one delivered through tiny aerosol particles to be inhaled deep into the lungs.

Part of a second generation of COVID-19 vaccines, this will be one of two Canadian-made formulae hoping to offer a more robust and more stable immune response. Results from Medicago Inc.'s Phase 3 trial of its plant-based vaccine that had involved about 24,000 people are due out shortly, as the final step of testing prior to potential approval. Trialled as a booster for people who have had two doses of an mRNA vaccine, the original focus was not as an adjunct to other vaccines.

In view of the SARS-CoV-2 virus being anticipated as a long-term threat, more booster doses are likely to result as a protection against its ongoing infectiousness and the possibility of additional mutated versions. Science recognizes the importance of testing new vaccines functioning in various ways, explained Dr.Smaill. For one thing, she points out, this mode of vaccine delivery will be welcomed by the needle-phobic, vaccine-hesitant public.

The delivery mechanism is built upon a previous twenty years of research on a tuberculosis vaccine that has been led by McMaster Professor Zhou Xing. The vaccine is designed to deliver a local "mucosal" response once inside the lungs, at the very site where the virus enters the body, with the aim of achieving a broader kind of immune response than can be seen by just injecting into the muscle of the upper arm. A more robust T cell response would be engendered; important since T cells find and destroy infected cells.

Strains of a weakened adenovirus, a family of viruses that cause the common cold, are contained in the vaccine. There are two currently being tested on 30 health volunteers; one a vaccine using a human adenovirus, the second a chimpanzee adenovirus. The vaccine targets two cellular proteins within the virus operationally required to have it grow and spread. "Mutations would be rarely seen in those proteins", explained Dr. Smaill.

Human trials are in the initial stages; however in the meanwhile, Medicago submits data to Health Canada as part of a rolling submission to be examined piecemeal. If early anecdotal reports suggesting Omicron causes milder infections are correct "I think we're going to be OK. We're all guessing what's actually going to happen", added Dr.Smaill, and hoping for the best possible outcome.