Characteristics of immune induction by transcutaneous vaccination using dissolving microneedle patches in mice

Transcutaneous immunization (TCI) is an appealing vaccination method. Compared with conventional injectable immunization, TCI is easier and less painful. We previously developed a dissolving microneedle (MN) patch and demonstrated that TCI using MN patches demonstrates high vaccination efficacy without adverse events in humans. In this study, we investigated the immune induction mechanism of TCI using our MN patch, focusing on inflammatory responses in the skin and on the dynamics, activation, and differentiation of various immunocompetent cells in draining lymph nodes (dLNs). We demonstrate that inflammatory cytokines such as IL-6 and TNF-alpha increased in the skin at an early stage after MN patch application, inducing the infiltration of macrophages and neutrophils and promoting the activation and migration of skin-resident antigen-presenting cells (Langerhans and Langerin- dermal dendritic cells) to dLNs. Moreover, the activated antigen-presenting cells reaching the dLNs enhanced the differentiation of T (Teff, Tem, and Tcm) and B (plasma and memory) cells. This may contribute to the efficient antigen-specific antibody production induced by TCI using MN patches. We believe that our findings reveal a part of the immune induction mechanism by TCI and provide useful information for the development and improvement of TCI formulations based on the immune induction mechanism.

Automated summary

Transcutaneous immunization (TCI) using dissolving microneedle (MN) patches is an efficient vaccination method with high efficacy and minimal adverse events. In this study, we investigated the immune induction mechanisms of TCI using MN patches, focusing on inflammatory responses in the skin and the activation and differentiation of immunocompetent cells in draining lymph nodes (dLNs). Our findings suggest that TCI using MN patches induces inflammatory responses in the skin, leading to the activation and migration of antigen-presenting cells to dLNs and promoting the differentiation of T and B cells for efficient antibody production.