A tiny molecule could unlock the potential of inhalable vaccines

Harissios Vliagoftis

In the future, a simple sniff could provide pain-free protection from the viruses that cause respiratory infections like influenza or COVID-19.

An inhalable vaccine is the goal of University of Alberta researcher and professor Harissios Vliagoftis. But he wants to go beyond current versions with a safer-for-all vaccine that doesn’t use a live virus.

The idea grew out of decades of asthma research Vliagoftis was conducting with a synthetic peptide molecule—“a very small protein”—that produced a surprisingly vigorous immune system response using animal models.

And that gave him an idea.

“The question was, ‘Can we use it for something else?’” Vliagoftis says. “And right away we came to the vaccination issue.”

"The most obvious advantage of an inhalable vaccine is the absence of a needle, removing the pain, fear and accompanying stresses."

After talking with Kevin Kane, an influenza infection and vaccine expert with the Department of Medical Microbiology & Immunology, they were able to develop a plan to test this synthetic peptide for nasal vaccines.

Specifically, Vliagoftis’ work targets a key imperfection with current inhalable influenza vaccines that requires them to be made with a live virus, which limits both their usefulness and their incredible potential.

The most obvious advantage of an inhalable vaccine is the absence of a needle, removing the pain, fear and accompanying stresses for children, parents and health-care providers alike," he says.

Less apparent is the reduced cost of a needle-free system, which could allow for mass vaccination programs in developing countries or among vulnerable populations.

The biggest advantage is the sheer effectiveness of delivering a vaccine directly to the part of the body that needs its protection. Inhaling an influenza vaccine, for example, brings it directly to the respiratory tract and lungs where viruses attach and cause infection.

“Usually we inject people through the skin and then the systemic effect of the vaccine comes back to the lungs,” he says.

“Very few vaccines go directly to the area where the protection will be important.”

But the Achilles’ heel of the inhalable delivery systems available in clinical practice today is that it only works with vaccines made from a weakened, live virus. For immune-compromised people, the live organism can be problematic—even if the vaccine is given to another household member, he says. “Although they’re not a full-strength live organism, they still have the ability to cause disease.”

That’s where Vliagoftis’ tiny peptide comes in.

All vaccines require a little extra material, called an adjuvant, to help boost immune response. The injectable influenza vaccine is made with inactivated, or killed, virus—it works well when injected into the skin but doesn't when it is inhaled through the nose. Vliagoftis' idea is to replace the adjuvant in the injectable vaccine with his tiny peptide. That, he hopes, would allow the preparation to be used as an inhalable vaccine.

“That’s what’s new in our case,” he says. “It is this alternate way to activate the immune system and instruct it to respond to the vaccine.”

Vliagoftis says the peptide agonist he is studying—a peptide that can activate a receptor called protease-activated receptor 2—has never been used in humans to trigger this specific immune response. Early data suggests it is safe and effective but clinical trials are still years away, he says.

But Vliagoftis says creating a new adjuvant to activate the immune system would be a significant milestone, with potential impact for other vaccines delivered to the body’s mucosal surfaces—or for other viruses altogether.

“We’re talking with some people even to try for COVID because that’s the big thing today,” he says. “Because maybe it will be effective for that—or for the next virus that will come down the line at some point.”

Harissios Vliagoftis is supported by the Stollery Children’s Hospital Foundation through WCHRI.