With the arrival of the highly contagious XBB.1.5 Omicron subvariant in Canada, some scientists say governments must invest more in developing mucosal vaccines — a tool that could be a game-changer in the fight against COVID-19.

Mucosal vaccines, which are inhaled in the nose or mouth, are widely considered by doctors and scientists to be the next generation in protecting against COVID-19 because they offer the greatest potential to prevent transmission of the virus — a feature that injected mRNA and adenovirus vaccines do not offer.

But while some countries, including China and India, have moved forward and authorized new inhaled vaccines, Canada is among the many nations that still do not yet have a mucosal vaccine against COVID-19 approved.

That’s something that needs to change soon if the country truly wants to return to some semblance of pre-pandemic ‘normal,’ says Dawn Bowdish, an immunology professor at McMaster University.

“Many of our policymakers and politicians have really thought that as soon as we get everyone vaccinated, we can just go back to normal,” she said.

“But until we get vaccines that actually stop transmission, we actually need to have a compromise between non-pharmaceutical interventions like masking and vaccination.… If we truly want to go back to a pre-COVID life, we are going to need to invest in mucosal vaccines.”

What’s the difference between injected and mucosal vaccines?

COVID-19 vaccines currently in use in Canada, such as those produced by Pfizer and Moderna, are injected into the arm’s muscle tissue and work by stimulating an immune response mainly in an individual’s blood.

This has proven to provide protection against severe infection that could cause hospitalization or death, but it does not always prevent transmission of the virus, Bowdish said.

Mucosal vaccines, on the other hand, can boost antibodies that line the respiratory tract, known as IgA antibodies, which then build an immune response in areas where the virus first enters and attaches to the body, says Marc-Andre Langlois, professor in the faculty of medicine at the University of Ottawa and executive director of the Coronavirus Variants Rapid Response Network.

That means mucosal vaccines target the virus at its first point of entry — the mouth and nose — and can stop it in its tracks before it has a chance to cause infection and transmission, Langlois said.

Langlois is leading a group of nine labs at the University of Ottawa to develop a mucosal vaccine that he says would act as a booster to those who have already received an existing mRNA COVID-19 vaccine.

“What we’re focusing on is really the point of entry, and we really want to attempt to complement the mRNA vaccines with a vaccine technology that is almost entirely dedicated to preventing the initial binding of the virus — that initial infection — and thereby reducing the transmission of the virus.”

Langlois and his team are producing vaccine ingredients from plants and are currently doing clinical testing of their prototype mucosal vaccine in mice.

So far, the results have shown success in boosting the IgA antibodies in mice that have been pre-administered mRNA COVID-19 vaccines, Langlois said. This means his prototype vaccine is “looking very promising as a booster to the current technologies.”

This project is among a small number of other studies being conducted in Canada on mucosal vaccines, including an inhaled vaccine trial under development at McMaster University.

But world health officials say more research and innovation in the area of mucosal vaccines is needed to make better headway in the fight against COVID-19.

“That really is the innovation that’s needed, so that we have products that are more effective than the current products are on the more mild end of the disease spectrum — the infection end of the disease spectrum, the transmission end of the disease spectrum,” Dr. Kate O’Brien, director of immunization, vaccines and biologicals for the World Health Organization, said during a WHO briefing Dec. 21, 2022.

“That’s something that we need to look forward to in 2023: greater investment, certainly, and a greater set of results coming out of those investments that have already been made.”

Why doesn’t Canada yet have a mucosal COVID-19 vaccine?

Langlois says one key reason why more progress hasn’t been made yet in developing a larger-scale mucosal vaccine is that the science in this area is still relatively new and has not yet been fully developed.

“In the field of immunology, still very little is understood about mucosal immunity,” he said.

“So it is a field that is understudied and therefore the vaccine candidates or prototypes that are being developed for stimulating mucosal immunity are still trying to bridge gaps in knowledge in how that works.”

That means the work he and others are doing to develop a newer, better vaccine that could prevent COVID-19 transmission is still “experimental,” as scientists do not yet know the best way to stimulate a mucosal immune response or what kind of antigens should be used, he explained.

“Therefore we are trying to do two things at the same time: develop the vaccines and fill in the gaps in our knowledge of mucosal immunity.”

Another uphill battle when trying to develop these kinds of new innovations is getting past existing technologies and practices, Bowdish said.

New inhaled vaccines would require a whole new infrastructure to deliver them, as they are not administered in the same way as current COVID-19 vaccines.

“The one that we’re working on at McMaster is inhaled, and so it’s not something you’ll be able to go and get a needle for. You’ll have to have the special inhaler that helps put the vaccine in there,” Bowdish said.

“But we need this kind of innovation. It’s clear that we’re winning a losing battle without this kind of innovation.”

Why more government funding is needed

Obtaining the necessary funding to make significant advances in these frontier scientific endeavours can be challenging, even as the global health emergency continues, Langlois said.

But the timing has never been more important, given freshly sparked concerns over new, deadlier variants of concern, he said.

Dr. Donald Vinh, a medical microbiologist at the McGill University Health Centre in Montreal, said it’s important to remember that scientific advances require the need to pursue multiple avenues of inquiry at the same time to “see which one sticks.”

This takes time and money.

“At the end of the day, when we need to develop vaccines, we need all hands on deck,” Vinh said.

“Whether that comes from philanthropy and foundations or government agencies or industry partners, I think we have to realize that it’s going to require that partnership.”

Dwindling uptake in current injected vaccines over the last two years in the West has led to diminished market demand for COVID-19 vaccines, which may have caused drug companies to put less priority on developing additional options, said Dr. Raywat Deonandan, epidemiologist and associate professor at the University of Ottawa.

But longer-term effects of COVID-19, including long COVID, mean that more investment in developing mucosal vaccines to prevent infection will be needed well into the future, he said.

“I think this has to be a priority for our biotech sector as it will be for our insurance sector and for other sectors.”

That’s why many doctors and experts say governments must do more to show leadership and fund more research and development of mucosal vaccines.

Currently, funding is available for this work through a variety of streams, including through the Canadian Institutes for Health Research, targeted provincial programs and grants, philanthropic entities and smaller, institutional grants.

But these are patchwork, short-term funding programs that do not provide the millions needed to allow research and clinical trials for mucosal vaccines like the ones at uOttawa or McMaster to scale up to their full potential, Bowdish said.

“What we really do need are direct investments, probably at the federal level, if not to the provincial level, to invest in new technologies, new innovation,” she said.

These kinds of investments would not only help advance the science to fight COVID-19, but the discoveries and technologies developed by these projects would also be useful to protect against other pathogens with pandemic potential, Bowdish said.

“This sort of investment is a future-proofing event.”

Langlois agreed, adding that without investment in better tools to better stop the transmission of COVID-19, the virus will continue to mutate and cause infection, illness and death across the country and the world.

Without a vaccine to effectively prevent infection, it also means the potential exists for more people to contract long COVID and other side effects of the virus, which are still not greatly understood, he said.

“There needs to be awareness at the government level and at the population levels that we haven’t reached a steady state yet. The virus is not what everyone seems to call endemic…. It’s not over yet,” he said.

“The virus still has an opportunity to evolve and therefore we have to continue developing technologies that will blunt its transmission and prevent it from causing chronic disease…. Investing in research is a benefit to us all.”