In a surprising twist on disease prevention, researchers have found that flossing—specifically with floss coated in vaccines—can trigger powerful immune responses in mice. The study, published in Nature Biomedical Engineering, suggests that a simple dental habit could become a needle-free way to guard against viruses like influenza.

“It sort of struck a spark,” Harvinder Gill, a nanomedicine engineer at North Carolina State University and senior author of the study, told Science. “If it is highly permeable, could we not use it for vaccination?”

Flossing Mice and Fighting the Flu

The idea started with the gums.

Decades of research have shown that viruses typically enter the body through the mucosal surfaces in your nose and mouth. But those entry points are notoriously difficult to use for vaccine delivery because of their natural barriers to foreign molecules. The gingival sulcus, the tiny crevice where your tooth meets your gum, turns out to be different. Its lining, known as the junctional epithelium, is unusually leaky. That permeability, combined with a high density of immune cells just beneath the surface, made it a promising target.

Gill and his team, including lead author Rohan Ingrole of Texas Tech University, set out to test this by doing something no one had done before: flossing mice.

It wasn’t easy. “Quite difficult,” Gill admitted. One researcher had to gently open the mouse’s jaw using a metal keyring while the other guided the vaccine-coated floss between its tiny teeth. But the results were remarkable.

When the team coated the floss with a fluorescently tagged protein, they found that the gum tissue absorbed roughly 75% of the dose. Even 72 hours later, the proteins were still visible in the mice’s gums—proof that the floss delivered its payload deep into immune-rich tissue.

The researchers went a step further. They added inactivated influenza virus to the floss and vaccinated 50 mice over 28 days. Four weeks later, they exposed all the mice to a lethal dose of the real flu virus.

The result? All vaccinated mice survived. Every unvaccinated mouse died.

“I had honestly never thought of using floss as a vaccination strategy,” said Akiko Iwasaki, an immunologist at Yale University who was not involved in the study. “The results are quite impressive.”

Systemic Immunity, Without a Needle

The flossed mice showed signs of robust immunity. Antibodies appeared in their saliva, feces, and in their bone marrow. T cells—immune cells that coordinate the body’s response to pathogens—were found in elevated numbers in the lungs and spleen. Their lymph nodes swelled, a classic sign of immune activation.

In some experiments, the vaccine even bypassed the need for dietary restrictions. Unlike oral vaccines that often require fasting to be effective, floss-based vaccination worked regardless of whether mice had access to food and water after immunization.

The study compared floss-based delivery with traditional methods. Floss outperformed drops placed directly on the gums and was roughly as effective as intranasal vaccination. Sublingual vaccines—those placed under the tongue—fared worse. Mice that received floss-based vaccines generated more antibodies and survived longer after viral exposure.

One reason for this success lies in the anatomy of the gumline. The junctional epithelium lacks the tight barriers found in most mucosal surfaces. It’s filled with immune cells like dendritic cells, Langerhans cells, and neutrophils, all of which help kickstart a strong immune response.

The researchers even explored the potential of a “universal” flu vaccine, coating floss with gold nanoparticles tagged with a conserved flu peptide (M2e). These floss-coated vaccines protected mice against multiple strains of influenza—even when they ate and drank water immediately after treatment.

Could This Work in Humans?

This is always a big question as mice studies don’t always translate to humans.

To see if the method might translate to people, the team asked 27 healthy volunteers to floss with dental picks coated in food dye, to see if the substance is absorbed. On average, 60% of the dye reached the gums—suggesting that vaccine delivery via floss is at least physically feasible in humans. Participants said they were generally open to the idea. Many said they’d even prefer it to a shot (what a surprise).

But there’s a caveat.

William Giannobile, dean of the Harvard School of Dental Medicine, who was not involved in the work, pointed out this is a “clever” approach. He added that we should observe how it performs in individuals with gum disease, which affects nearly half of American adults. Inflamed or damaged gums could change how well the vaccine is absorbed.

Other scientists echoed the need for more testing. James Crowe, an immunologist at Vanderbilt University who was not involved in the study, said that clinical trial testing is needed to definitively determine whether this proof-of-concept approach is viable.

Floss-based vaccines would come with unique benefits. They don’t require needles, refrigeration, or specialized training to administer. That makes them easier to distribute—possibly even by mail—in future pandemics.

“Imagine going to the dentist,” said Giannobile. “And your provider administers one of these vaccines during your visit.”

For now, the approach remains experimental. But it joins a growing list of alternative vaccination methods aiming to make disease prevention easier, cheaper, and more accessible.