A preclinical study in mice found that vaccines delivered to the gingival sulcus using coated dental floss induced strong mucosal and systemic immune responses and provided protection against lethal influenza infection.
The gingival sulcus, located between the tooth and gum, contains the junctional epithelium, a tissue with high permeability and abundant immune cells. Researchers coated flat tape dental floss with various vaccine formulations, including inactivated influenza virus, protein antigens, peptide-presenting nanoparticles, and messenger RNA, and applied it to the gingival sulcus of mice.
Using ovalbumin as a model antigen, floss delivery produced higher antigen-specific IgG and IgA responses in serum and mucosal sites compared with unvaccinated controls. Adding the adjuvant CpG further enhanced antibody levels and promoted a Th1-type immune profile.
When inactivated influenza virus was delivered via floss, three doses produced the highest systemic antibody titers and mucosal IgA responses. Mice given three doses of either 10 or 25 µg were completely protected from a lethal influenza challenge, while two-dose regimens provided partial protection.
Testing a nanoparticle influenza vaccine targeting the conserved M2e epitope, floss-delivered M2e-AuNP + CpG generated higher antibody levels than unvaccinated controls and was superior to sublingual delivery. All floss-vaccinated mice survived lethal challenge with pandemic H1N1 influenza virus, regardless of access to food and water after immunization.
In comparisons with intranasal vaccination, floss-based delivery produced similar systemic antibody levels, though intranasal vaccination induced higher IgA at some mucosal sites. Both routes provided complete protection against lethal H1N1 and heterosubtypic H3N2 influenza challenges.
Mechanistic analysis showed that floss vaccination activated cervical lymph nodes within hours, increasing cytokine and chemokine expression important for immune cell recruitment. Ten days after the second immunization, floss-vaccinated mice had increased CD4+ T cell populations in cervical lymph nodes, lungs, and spleen, and produced multiple cytokines upon antigen stimulation. Bone marrow cultures secreted antigen-specific antibodies without further stimulation, indicating the presence of antibody-secreting cells.
Harvinder Singh Gill, PhD, of the Department of Chemical and Biomolecular Engineering at North Carolina State University, and colleagues, stated, “These findings establish floss-based vaccination as a simple, needle-free strategy that enhances vaccine delivery and immune activation compared with existing mucosal immunization methods.”
A feasibility test in human volunteers using floss picks coated with fluorescent dye showed that the dye reached the gingival sulcus, supporting potential clinical application.
Study limitations included its preclinical design, use of influenza models only, and lack of long-term immunity data. The effect of repeated floss-based immunization on gum health in humans remains unknown.
The researchers concluded that targeting the gingival sulcus with coated floss could provide a simple, needle-free method for delivering vaccines capable of inducing both local and systemic immunity. Clinical trials will be needed to evaluate safety and effectiveness in humans.
Full disclosures can be found in the published study.
Source: nature biomedical engineering
