Here’s a no-jab way to get vaccinated. Just open your mouth and floss. This approach works well in mice, scientists report. They hope a version for people could work, too.

Not all vaccines are delivered with a needle. Some target the moist tissues in our bodies. Known as mucus membranes, we have them in our mouth and nose. Germs often invade the body through these mucus membranes. Building immune defenses in these parts helps disarm viruses upon entry. The flu virus, for example, usually enters our body through the nose. Then it heads toward the lungs.

Protecting mucus membranes can be challenging. These moist tissues come into direct contact with the air and germs around us. Their cells are tightly packed to help keep pathogens out. But that can make it tricky to get a vaccine in and prompt an immune response. 

Researchers have designed vaccines before that target places in the mouth, where cells aren’t quite as close together. To do this, they used cheek patches or liquid drops under the tongue.

Harvinder Gill, a bioengineer at North Carolina State University in Raleigh, came up with another idea. While reading a paper on dental structure, he learned about a leaky collection of cells at the base of a small pocket, where gums attach to teeth. Maybe here, he thought, is where his team should try to introduce a vaccine.

There’s just one problem. This pocket — the junctional epithelium — sits below the gumline. That makes it hard to reach.

“We needed something more precise [than a drop of liquid],” Gill says. “And then we thought ‘Oh, hey, we already have floss. … Why don’t we just use [floss] to also deposit the vaccines into this location?”

He proposed testing this in mice. But that immediately raised the issue: How do you floss a mouse? No one had ever done that. Rohan Ingrole, a bioengineer at Texas Tech University in Lubbock, accepted the challenge.

That led to even more questions. What’s the best way to open a mouse’s mouth? How does one get the floss in the right spot? And is there a way to protect the mouse’s gums from damage?

Initial tests flopped. While gently moving the floss back and forth over the bottom front teeth (incisors), the animals’ jaws dropped down. Right away, the floss slipped out.

“One day, after a failed attempt, I was just going around [the lab] and I saw this key chain lying on the table,” Ingrole recalls. “It made me wonder: Can I use the ring of this key chain to provide support to the mouse jaw?” That, he now says, “turned out to be a game changer.” 

It worked. Yet even with this support tool, flossing a mouse is a two-person job.

First, the mouse must be lulled into deep sleep with an inhaled anesthetic. Then, one person must gently hold the mouse in an upright position by the scruff of its neck. That person also pops the mouse’s head through the key ring. This allows the animal’s lower jaw to stay open and rest against the ring’s edge. The second person then plays dental hygienist with a vaccine-coated piece of floss.

Promising initial data

That floss had been coated with a vaccine made from dead flu viruses or lab-made bits and pieces of them. With each swipe back and forth, that floss delivered the vaccine through the gum’s junctional epithelium.

The team tried four different types of vaccines. All boosted immune defenses in the mice. Eating or drinking right after flossing didn’t affect how well the vaccine worked. What’s more, the flossed vaccine was similar to a vaccine inhaled through the nose.

Giving vaccine with floss may even be a bit safer than a nasal mist. Why? Noses have a direct connection to the brain, Gill notes. So safety tests of nasal vaccines must show there’s no big risk of side effects in the brain. Vaccines given through the gums, by contrast, are unlikely to reach the brain.

Gill and Ingrole’s team shared its new findings July 22 in Nature Biomedical Engineering.

“It’s very clever, I like the strategy,” says Stephanie Langel. She’s a viral immunologist who did not take part in the new work. Langel works at Case Western Reserve University. That’s in Cleveland, Ohio.

Several signs of immunity

Both nasal and floss vaccines triggered immune defenses in the blood of mice. So both vaccines may help prevent severe disease and death. But compared to the floss vaccine, the nasal type caused more antibodies to hang out in mucosal linings (such as those in the nose), the new study found. And that means nasal vaccines might be better at preventing one individual from passing a virus to another, Langel says.

Here’s why they think this flossing vaccine delivery may work in people too.

The floss vaccine might be improved, however, by adding the right adjuvant (ADD-ju-vunt). This is some chemical or other material that boosts the body’s immune response to some foreign substance. This might help the body make more antibodies in places like the saliva or nose. In turn, that should protect against invading germs.

The floss vaccine has been tested in 27 human volunteers. The researchers coated a one-handed floss pick with a dye. It glows under UV light. Then the volunteers flossed their teeth. Afterward, the researchers used UV light to search for the dye. Flossing had deposited roughly 60 percent of the floss’ vaccine into people’s gum pockets, they found.

Now the goal is to make flossing easier, Gill says, and to ensure that people are getting a consistent dose.

Such vaccines might one day provide a painless, needle-free way to vaccinate, he says. And if people are comfortable with flossing their teeth with a vaccine, they could do it at home.

In fact, self-vaccinations could be huge during a pandemic, Ingrole says. During the COVID-19 pandemic, scores of health-care workers had to help with vaccination efforts. “Imagine if you had this vaccine that could just get delivered at your doorstep,” Ingrole says. To get a vaccine, he notes, you’d “no longer have to go stand in line for hours.”  

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