Oral Mucosal Vaccination Using Coated Microneedles

The oral cavity has significant potential as a mucosal vaccination site because it is easily accessible and is immunologically attractive due to the presence of several lymphoid tissues in the oral cavity that could potentiate a robust immune response. Despite these advantages, the oral cavity remains under-utilized for vaccination due to the difficulty of delivering vaccine antigens across the tough transport barrier formed by the stratified epithelium covering the oral cavity tissues and the poor residence time due to salivary flow. We present the first study demonstrating the use of coated microneedles for enhancing vaccine delivery to the oral cavity using a rabbit animal model. In this study, we tested the ability of coated microneedles to penetrate the oral cavity tissues, specifically the inner lower lip and the dorsal surface of the tongue. Penetration of microneedles into tissues was confirmed by histological analyses. Delivery efficiency of coatings was found to be 63.9% and 91.2% for the lips and tongue respectively despite the moist environment in the oral cavity. Ovalbumin-coated microneedles were inserted into the lip and the tongue of rabbit to evaluate the immune response by direct delivery of antigens to the oral cavity tissues. Significantly higher (p<0.05) ovalbumin-specific IgG antibodies were found in serum. However, the increase in mucosal IgA antibody secretions was marginal (p>0.05). In addition, no significant difference (p>0.05) was observed between the lip or the tongue as the site for vaccination. In conclusion, this study provides the first validation of the use of microneedles for delivery to the oral cavity with specific focus on vaccination to induce both systemic and mucosal immunity using antigen-coated microneedles as minimally invasive devices for oral cavity vaccination. This methodology could form the basis of delivery of safe adjuvants to the oral cavity to further potentiate mucosal immunity.