(486c) Screening Microneedle Formulations for Influenza Vaccine Stabilization

Influenza is a potentially life-threatening infectious disease that causes up to 5 million cases of severe illness annually during seasonal epidemics in the US alone. Microneedle (MN) patches are designed to deliver vaccines, such as influenza vaccine, to the skin where there is an abundance of antigen-presenting cells, thus eliciting similar or improved immune response when compared to conventional intramuscular injection.

Dissolving polymer MN are projections that measure hundreds of microns in length, which are composed of water-soluble polymer with a vaccine payload embedded along with formulation excipients such as stabilizers and dissolution enhancers.  These MN dissolve within minutes upon insertion into skin, thereby releasing their vaccine payload.  However, influenza vaccine can be damaged due to the drying process during manufacturing and instability during storage. The excipient formulation is critical to maintaining vaccine antigenicity during the drying and storage of MN patches. This study addresses stabilization of influenza vaccine in microneedle patches during storage at elevated temperature, which will facilitate mass distribution for annual and pandemic influenza vaccination campaigns.

In this study, we have developed a high-throughput screening method to optimize microneedle formulations for influenza vaccine stability.  Producing MN arrays is time consuming, thus requiring a faster method for screening formulations.  We have addressed this bottleneck by using flat, 6 mm-wide, polydimethylsiloxane (PDMS) “chips” as a surrogate for the molds used to form MN.  Test formulations are dried and stored on the surface of these chips and then tested for vaccine activity.  Our method for assessing vaccine activity is an ELISA, used to quantify the amount of antigenic protein, hemagglutinin, still in the native conformation.

A large number of compounds were screened against their ability to retain influenza vaccine activity. Through this study, several promising formulations were found to maintain vaccine activity for at least 3 months at 40°C.  These were comprised of suitable buffers and stabilizing compounds including sugars, amino acids, and long-chain carbohydrates.  The best formulations thus far utilized a combination of stabilizers where the combination performed better than the constituent single stabilizers.  Long-term stability experiments in MN patches are underway and will be reported in this presentation. In addition, experiments to elucidate the mechanism of activity loss and retention are being conducted.