Inhalable COVID-19 vaccine could expand the reach of COVID-19 vaccines around the world

What if you could get vaccinated against the virus that causes COVID-19 with an inhaler instead of a needle? That’s the premise behind new research by Northeastern’s Paul Whitford. Photo Illustration by Alyssa Stone/Northeastern University

Scientists have come up with a new way to get vaccinated against the coronavirus that causes COVID-19, and it comes with a twist: No needles needed.

This vaccine would instead be aerosolized so it could be inhaled by a patient.

Paul Whitford, associate professor of physics in the College of Science and the Center for Theoretical Biological Physics at Northeastern. Courtesy Photo

Researchers have tested this vaccination strategy in mice, and it elicited a strong immune response. A team led by researchers from Northeastern University, Rice University, and Rutgers University published a proof-of-concept study in the journal Proceedings of the National Academy of Sciences this week. The project is still in early stages, but the team sees the vaccine they’re developing as a way to expand the reach of COVID-19 vaccines around the world.

“If we can have this new tool, that would be great. It’s easy to produce, easy to ship, easy to administer,” says Paul Whitford, associate professor of physics at Northeastern and an author on the new paper. Such an inhalable COVID-19 vaccine wouldn’t require the precise refrigeration of existing inoculations, and could be dispersed more easily to rural and remote communities. “You just need basic instructions on how to use an inhaler.”

The team’s vaccine strategy uses modified bacteriophage particles to deliver instructions to the immune system—via the lungs—to develop a protective response to SARS-CoV-2, the coronavirus that causes COVID-19.

Bacteriophage particles (or phage particles for short) are viruses that infect bacteria but are safe for humans, and have been used to treat bacterial infections in humans for a century.

In this new vaccine strategy, a phage particle in the immunizing mist is kind of like a visitor knocking on the door of the lung tissue. It has an arm reaching out to greet the lung tissue and a backpack filled with immune instructions on its back, Whitford explains.

The phage particles have been modified to contain a protein (the metaphorical arm) that the lung cells will recognize and pull into the recipient’s bloodstream. “You need to put a hand out there and be like, ‘Let me in!’” he says. “And then, ‘Okay, I’ve got something for you.’”

That “something” is precious cargo: tiny pieces of the spike protein from SARS-CoV-2. But it’s not just any piece. This is what’s called an “epitope.” It’s the part of the invasive protein where an antibody can attach itself to the offending viral cell to keep it from infecting one of our cells.

The idea is to deliver these parts of the virus to the body’s immune system to give it a sort of practice run in fending off SARS-CoV-2. That way, Whitford says, if you’re exposed to the real virus, your immune system will know what to do immediately.

But there’s a wrinkle. The spike protein contains many different epitopes. And some of them lose their shape (and thus their properties) when you remove them from the rest of the virus.

So Whitford and his colleagues at the Center for Theoretical Biological Physics, housed at both Northeastern and Rice, turned to supercomputers. The team ran simulations of what would happen when some selected epitopes were transferred to a phage. Their analysis identified which epitope would retain its structure and best train the immune system to attack the real SARS-CoV-2. Then, the experimental team at Rutgers developed the vaccine and tested it on mice.

“Practically, experimentally, you can’t build a thousand vaccine candidates and test all of them just to see which one works,” Whitford says. “You can’t use that many mice just to see if it will work.”

The newly published study is largely preliminary, as there are many more epitope candidates that the team has yet to examine. Sorting through all of the possible configurations using the supercomputers is the next step, Whitford says. “This study provides a sort of proof-of-principle that this is a decent strategy,” he says. “That was our first pass.”

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