Flossing may be good for more than getting your dentist off your back—one day, it may also protect you from the flu. In an unorthodox approach to needle-free vaccines, researchers have developed a special kind of floss that can deliver proteins and inactive viruses to mice’s gumlines and trigger immune responses that protect against infectious disease, they report today in Nature Biomedical Engineering.
“I had honestly never thought of using floss as a vaccination strategy,” says Akiko Iwasaki, an immunologist at Yale University who was not involved in the work. “The results are quite impressive.”
For many years, scientists have tried to develop alternatives to delivering vaccines via syringes by turning to the moist areas in your mouth and nose where most viruses enter. But it’s tough to develop an effective vaccine that can be administered through those entry points because they have naturally tough defenses against foreign molecules, says Vanderbilt University immunologist James Crowe, who was not involved in the work.
The new approach could circumvent these defenses. Years ago, Harvinder Gill, an engineer at North Carolina State University who specializes in nanomedicine, was reading about gum disease when he stumbled across a paper that said the gingival sulcus—the pockets of gum between the sides of your teeth—could absorb molecules extremely well. “That sort of struck a spark,” says Gill, the new study’s senior author. “If it is highly permeable, could we not use it for vaccination?”
To test this idea, Gill and Rohan Ingrole, first author of the paper and a chemical engineer at Texas Tech University, had to do something no scientist had done before: Try to floss a mouse. It was a “quite difficult” two-person job, Gill says: One scientist gently pulled the mouse’s jaw down with the metal ring from a keychain while the other administered the floss.
During a test run, the team found that when researchers coated floss with a fluorescently labeled protein, 75% of the protein was successfully delivered to the mouse’s gums. And even 2 months after flossing, the mice had elevated levels of antibodies in their lungs, noses, feces, and spleens, suggesting a robust immune response to the protein.
Next, the engineers added an inactive flu virus—a common vaccine component—to the floss, which in theory could teach the mouse’s body to build up immunity to the flu. Over a 28-day period, the researchers flossed 50 mice with the coated floss every 2 weeks. Then, 4 weeks after the final dose, they infected those mice with the real flu virus. All the mice that were flossed three times survived, whereas all the unvaccinated mice died.
The flossed mice also had a more systemic immune response: Not only were flu antibodies present in their feces and saliva, but the mice had more T cells—the directors of the body’s immune response—in their lungs and spleens, as well as larger lymph nodes. What’s more, the team found flu antibodies in the mice’s bone marrow, signaling that their immune systems were “fully engaged” by the inactive flu virus, Gill says. Overall, the immune response to the floss resembled the response to vaccines that are sprayed into the nose, such as FluMist.
To gauge whether the method could work in humans, the researchers asked 27 healthy volunteers to floss with dental picks coated with colored food dye. On average, roughly 60% of the dye was delivered to the participants’ gums. They then surveyed the participants on what they thought of the approach. Most said they were open to trying a floss-based vaccine and would prefer it to a shot.
The approach is “clever,” says William Giannobile, a periodontics researcher at the Harvard University School of Dental Medicine who was not involved in the work. But he was surprised to see such a systemic immune response in mice. In humans, he would like to see how the technique fares in volunteers with more variation in gum health, to see whether the 40% of American adults with gum disease could also use the product. And Crowe says clinical trial testing is needed to definitively say whether this proof-of-concept approach is viable.
Gill and his team hope to continue to refine the technology—and Giannobile, for one, is curious to see how their work unfolds. “You could imagine going to the dentist,” he says, “and your provider administers one of these vaccines during your visit.”
