DESCRIPTION (provided by applicant): It is widely recognized that the young and elderly represent two population groups at high risk from influenza virus infection. Morbidity and mortality from influenza-related illness and secondary complications are highest in these groups. Although current influenza vaccines are relatively effective in eliciting protective immune responses in adults, they only confer limited protective immunity in the young and aged. The reasons for the reduced efficacy in these groups could be a result of various factors including reduced potency/immunogenicity of split and subunit influenza vaccines, the lack of prior exposure and immaturity of the immune system observed in young individuals and the immunosenescence observed in the elderly. The current intramuscular route used to administer these vaccines may also be less effective for antigen uptake and presentation due to the reduced interaction with MHC II immune cells, thus limiting the magnitude of the immune responses. In order to improve vaccine efficacy in these high risk groups we propose to determine if delivery of influenza vaccine through the skin of the young and aged can confer improved immune responses and protection when compared to intramuscular immunization. We plan to build on our preliminary data and previous studies, and take advantage of our extensive experience with different types of microneedle designs and technologies and unique animal models to successfully complete this project. We are motivated by our findings that skin microneedle delivery of existing FDA-approved influenza vaccine formulations can enhance the immune responses in animal models and confer improved protection when compared to intramuscular immunization in the young and aged. Thus, our research has the potential to suggest new vaccination approaches and immunization strategies that will impact and improve public health globally.

PUBLIC HEALTH RELEVANCE: This project will demonstrate the efficacy of new vaccination routes for influenza vaccine delivery to confer improved protection in the young and aged. As a result, we will obtain important new insights into design of new immunization practices and strategies for these high risk groups that can will prevent influenza infection and improve public health.