Floss-based Vaccination Shows Promise as Needle-free Strategy

North Carolina State University researchers have demonstrated a new approach to vaccine delivery in animal models by using dental floss to introduce vaccine into the tissue between teeth and gums. Their work demonstrates that this method stimulates production of antibodies on mucosal surfaces such as those lining the nose and lungs, which are essential entry points for pathogens like influenza and COVID. According to Harvinder Singh Gill, corresponding author of the study published in Nature Biomedical Engineering, “if a vaccine is given by injection, antibodies are primarily produced in the bloodstream throughout the body, and relatively few antibodies are produced on mucosal surfaces.” Vaccination through mucosal routes, in contrast, boosts the presence of antibodies both systemically and directly where pathogens often first invade.

The study focused on the junctional epithelium, a thin and more permeable layer of tissue at the base of the gum pocket. Unlike other barriers in the body, the junctional epithelium permits the passage of immune cells to combat bacteria, making it a unique target for vaccine introduction. “Because the junctional epithelium is more permeable than other epithelial tissues—and is a mucosal layer—it presents a unique opportunity for introducing vaccines to the body in a way that will stimulate enhanced antibody production across the body’s mucosal layers,” says Gill.

To test their hypothesis, researchers delivered a peptide flu vaccine via unwaxed dental floss to the junctional epithelium of lab mice, comparing the immune response to that produced by nasal administration and sublingual (under the tongue) application. According to first author Rohan Ingrole, “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.” The flossing method also offered protection against the flu comparable to intranasal vaccination, without the risk of vaccines reaching the brain, a potential concern with nasal delivery.

The researchers further tested the floss-based delivery for proteins, inactivated viruses, and mRNA vaccines, finding robust antibody responses in both mucosal and blood samples. Notably, eating and drinking soon after flossing did not diminish the immune response.

Moving toward practical human application, the team used floss picks and fluorescent dye in a trial with 27 participants. Results showed that about 60% of the dye reached the intended gum pocket, supporting the feasibility of using floss picks for vaccine delivery. Gill notes that while the technique would not work for individuals without teeth or those with certain oral health conditions, it could offer easy, needle-free vaccination for many people, with a cost similar to other delivery methods.