Hypodermic needles remain the most common method of administering lifesaving vaccines, but that doesn’t mean receiving the jab has gotten more pleasant over time. Now, biomedical engineers are exploring a new approach that could ditch shots entirely for a far more mundane delivery system: dental floss. Their initial findings are laid out in a study recently published in the journal Nature Biomedical Engineering.
Needles are an understandable go-to for many vaccines and boosters—they’re effective, quick, and easy to use. But shots still have their drawbacks. Used syringes are biohazards, and needles often remain a difficult sell for anyone with a phobia or low pain threshold. Their efficacy is also sometimes limited due to where antibodies are produced. While hypodermic vaccines primarily stimulate antibody creation in the bloodstream, many pathogens like influenza and COVID still enter the body through the nose and mouth.
Nasal sprays aren’t enough
In recent years, researchers have developed a number of nasal spray vaccine alternatives. Even then, these variants are frequently limited because they have trouble breaching the epithelium—an interior tissue lining designed to block viruses, dirt, and dust from entering the bloodstream. The epithelium coats not only regions like the lungs, intestines, and stomach, but the deepest pocket between your teeth and gums. Unlike in other parts of the body, however, this junctional epithelium doesn’t feature that same protective barrier. And that’s where a team at North Carolina State University thinks they’ve found a backdoor for vaccine delivery.
Without that protective barrier seen elsewhere in the body, the junctional epithelium is more permeable than similar tissues. It’s also a mucosal layer, which means introducing vaccines there will boost antibodies where they are often needed the most.
“It presents a unique opportunity for introducing vaccines to the body,” explained Harvinder Singh Gill, an NCSU biomedical engineer and study corresponding author.
While the junctional epithelium lacks the protective lining, Gill and colleagues believe this could work in a patient’s favor. Without it, the region is open to release bacteria-fighting immune cells into your mouth—as well as any vaccine-induced antibodies.
Mouse flossings
To test their theory, researchers applied a traditional peptide flu vaccine to unwaxed dental floss, then oversaw a teeth cleaning session for lab mice. To compare its efficacy, they also enlisted two other groups of rodents to receive the same vaccine, either through the nasal epithelium or the mucosal tissue under their tongues. The results were clear.
“We found that applying vaccine via the junctional epithelium produces far superior antibody response on mucosal surfaces than the current gold standard for vaccinating via the oral cavity, which involves placing vaccine under the tongue,” said study first author Rohan Ingrole. “The flossing technique also provides comparable protection against flu virus as compared to the vaccine being given via the nasal epithelium.”
The team also reported an additional benefit over the existing nasal epithelium delivery system—it keeps the brain safe from harm. Occasionally, intranasal vaccines have the potential to reach the brain and cause complications. According to Gill, the junctional epithelium method “offers no such risk.”
What’s particularly promising is that, for their initial experiments, Gill’s team used one of the few vaccine formulations that is actually effective through nasal delivery.
“We wanted to see how junctional epithelium delivery compared to the best-case scenario for nasal delivery,” he explained.
Researchers also didn’t stop at the flu vaccine. Instead, they also tested the floss delivery for three other major vaccine classes—inactivated viruses, mRNA, and proteins. Each time, the epithelial junction offered an effective site for introducing antibodies into the bloodstream and across mucosal surfaces. The mice immunoresponse even remained the same if they ate or drank shortly after receiving their flossing.
A pain-free alternative
Lastly, the team asked a small group of human volunteers to floss with floss picks coated in fluorescent food dye after explaining how to reach the epithelial junction in their gums.
“We found that approximately 60 percent of the dye was deposited in the gum pocket, which suggests that floss picks may be a practical vaccine delivery method to the epithelial junction,” said Ingrole.
Gill and Ingrole next plan to review their findings along with additional research before considering a clinical trial. While they’re optimistic about their innovation, they know the approach has its caveats. Flossing only works when you actually have teeth, so the method isn’t applicable to infants and toddlers. Meanwhile, more investigation is needed to determine if issues like gum disease and other oral infections might impede a vaccine’s efficacy.
While no single vaccine delivery system is perfect for every patient, introducing the comparatively pain-free, easy-to-use flossing alternative could one day help substantially improve vaccine and booster rates in the process. And better vaccination rates vastly improves overall public health.
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