McMaster University’s inhaled COVID-19 vaccine begins phase-2 human trials

Researchers at McMaster University in Hamilton, Ontario, have developed a home-grown COVID-19 vaccine with no need for needles.

The mucosal vaccine is administered directly to the lungs by inhaling it, rather than injecting. It has been in the works since the global pandemic was declared in 2020, using the learnings from decades of research on mucosal immunity and vaccine work on tuberculosis.

“We are really looking at a paradigm shift. How can we think about giving vaccines differently? And a lot of the work we’ve done here at McMaster has demonstrated how, if you immunize through the mucosal route, that is into the lungs, you can generate an immune response in the lungs, which is really where you need it for these respiratory infections,” explains lead researcher Dr. Fiona Smaill.

Clinical studies on the vaccine, called ChAd-triCoV/Mac, are currently underway. Phase one of human trails have been completed.

“Most people now will have had COVID or had a vaccine or both. The work we did in our phase-one study showed that even if you had been vaccinated or had a COVID infection, we couldn’t find immune cells in the lung that were going to be likely associated with protection. But when we gave the vaccine to our phase one participants and then studied the immune cells in the lung, we could show that we had generated some of these cells. And that’s why we’re excited about this as a different approach to managing this type of respiratory infection,” says Dr. Smaill.

Phase two of the trials, called the AeroVax study, is now recruiting participants.

“[Phase one] showed that we could give [the vaccine] safely to healthy volunteers. And we were able to measure in the lung immune responses that were likely to be effective and protect against a COVID infection. So now we are embarking on the phase-two study to really evaluate the vaccine in a larger number of people and again, demonstrate that the vaccine is safe and get a better sense of what the immune responses are going to be like,” says Dr. Smaill.

Researchers are hoping to recruit 350 participants across Hamilton, Ottawa and Halifax for the AeroVax study.

What does the inhaled vaccine contain and how does it work?

ChAd-triCoV/Mac is viral vector-based, and uses the adenovirus as a delivery vehicle. Genes from the COVID virus are spliced into the adenovirus, which then carries the COVID material into the body.

“When the body’s immune cells see that adenovirus, it doesn’t know that it’s a vector as compared to ordinary adenovirus and it generates an immune response to it,” says Dr. Smaill.

“The vaccine that we’ve manufactured has got three antigens, three parts of the COVID virus, and by having a broader range of antigens, we anticipate that that’s going to give a more robust and broader immune response.”

The immune response to the vaccine involves T-cells that destroy harmful pathogens, B-cells that generate antibodies and what’s known as an innate immune response.

“What happens with the innate immune system is it’s not specifically focused on just one virus or just one bacteria. And in our phase-one study, we’ve been able to see that we can generate this so-called innate immune response and that has a number of advantages. It may mean that you’re protected against another virus that happens to come along, it also makes it probably better at managing some of the variants. So if a strain changes enough, then you may end up relying on the innate immune response as well. The mRNA vaccines given intramuscularly don’t generate this [innate response].”

It’s important to note that there is no live COVID virus in the vaccine.

“And in fact, the adenovirus that we are using has been further manipulated in the lab so that it won’t continue to grow. It does one cycle and then it stops. We call it ‘non-replicative,’ so it’s not going to continue to grow in the body. We just want it to do it one time so that you can generate that immune response, and it’s those immune cells which are the ones that we need for protection,” explains Dr. Smaill.

How is the inhaled vaccine administered?

The new vaccine is administered using a specialized inhaler which is different from puffers used for other inhaled medications.

“It’s important when we give the vaccine that we make the particles that we inhale tiny enough that they go down deep into the lung. And so to do that, we need a special nebulizer … to generate this fine mist of the vaccine,” says Dr. Smaill.

The apparatus is called an “aerojet” and consists of a small chamber into which the liquid vaccine is deposited and a mouthpiece for inhalation inhaled.

When the device is turned on, a membrane between the chamber and mouthpiece begins to vibrate at a high velocity, which converts the liquid vaccine into a fine mist to be inhaled. Inhaling one full dose takes about two minutes.

Dr. Smaill says the amount of vaccine used when given through this nebulizer is 100 times less than the amount used in an injection, which is relevant when it comes to manufacturing and cost per dose.

In addition, she says it works better directly administered to the lungs and is helpful for those who are needle-phobic.

“If there’s options that are actually better, then that really broadens the opportunity to provide effective vaccines to the population,” she says.

Dr. Smaill says if subsequent trials and further development continue as expected, they hope to bring the vaccine to market in the next five years.