Improved Influenza Vaccine Efficacy Through Infection Mimicry

Project Summary Abstract The World Health Organization estimates that influenza viruses cause serious illness intomillion people and up todeaths globally each yearWhile seasonal vaccines to prevent influenza infection are availablefrequent mutations in the virus require manufacturers to guess which strains will circulate each season and reformulate vaccine on an annual basisAs a resultthe public health impact of seasonal vaccines is limited due to challenges with product efficacyestimated atfor theseasonThis challenge highlights the critical need for improving current influenza vaccines through strategies to both improve humoral responsesonsetmagnitudeand breadthand generate additional responses such as mucosal immunity and CDCDcellular responsesOur technology focuses on engineering the sustained release of seasonal influenza vaccines to mimic infection kinetics overweeksproviding greater breadth of anti influenza antibodies and inducing T cell responsesThis is accomplished through the use of silk fibroin biomaterial in a microneedle array format that can be easily administered to the skinThe design of the microneedles is such that after a briefminute wear timethe silk microneedle tips are released from the patch and are embedded in the dermisThese silk tips have been engineered to both stabilize vaccine antigens at body temperature while slowly releasing this payload overweeksOur central hypotheses includesustained antigen presentation mimicking natural infection kinetics can enhance influenza vaccine responsesincluding greater breadth of protectionandmicroneedle delivery could simplify patient administration while also improving antigen delivery to immune cells in the skinThese hypotheses are supported by our preliminary data with this strategydemonstrating significant improvements to the humoral and cellular responses elicited by influenza vaccinationAs suchwe aim to advance our product towards the clinic through further optimization of the composition of our silk microneedles and by demonstrating their immunogenicitymanufacturabilityand safety in IND enabling studiesSuccessful completion of our objectives will position the technology for a Phase I clinical trial with the ultimate goal of reducing the global burden of influenza Project Narrative Improved strategies to enhance the efficacy of seasonal influenza vaccines would provide an important step forward in reducing the global burden of this diseaseThe proposed work will address this need by mimicking natural infection with sustained release silk microneedles to increase immune responses to current influenza vaccines