Oral mucosal vaccination using integrated fiber microneedles

The oral mucosa is an attractive site for immunization due to its accessibility and ability to elicit local and systemic immune responses. However, evaluating oral mucosal immunogenicity has proven challenging due to the physical barriers and immunological complexity of the oral mucosa. Microneedles can overcome these physical barriers, but previous work has been limited in the scope of microneedle delivery site, geometry, and release kinetics, all of which are expected to affect physiological responses. Here, we develop integrated fiber microneedle devices, an oral dosage form with tunable geometries and material configurations capable of both burst and sustained release to controlled depths in the oral mucosa. Integrated fiber microneedles administered to either the buccal or sublingual mucosa result in seroconversion and antigen-specific interferon-γ secretion in splenocytes. The dynamics and magnitude of the resulting immune response can be modulated by tuning microneedle release kinetics. Optimal microneedle geometry is site-specific, with longer microneedles eliciting greater immunogenicity in the buccal mucosa, and shorter microneedles eliciting greater immunogenicity in the sublingual mucosa. The Th1/Th2 phenotype of the resulting immune response is also dependent on integrated fiber microneedle length. Together, these results establish integrated fiber microneedles as a multifunctional delivery system for the oral mucosa and motivate further exploration using tunable delivery systems to better understand oral mucosal immunity.