Mortality due to seasonal and pandemic
influenza could be reduced by increasing the speed of
influenza vaccine production and distribution. We propose that vaccination can be expedited by (1) immunizing with influenza virus-like particle (VLP)
vaccines, which are simpler and faster to manufacture than conventional egg-based inactivated virus
vaccines, and (2) administering
vaccines using microneedle patches, which should simplify
vaccine distribution due to their small package size and possible
self-administration. In this study, we coated microneedle patches with
influenza VLP
vaccine, which was released into skin by dissolution within minutes. Optimizing the coating formulation required balancing factors affecting the coating dose and
vaccine antigen stability. Vaccine stability, as measured by an in vitro hemagglutination assay, was increased by formulation with increased concentration of
trehalose or other stabilizing
carbohydrate compounds and decreased concentration of
carboxymethylcellulose (CMC) or other viscosity-enhancing compounds. Coating dose was increased by formulation with increased VLP concentration, increased CMC concentration, and decreased
trehalose concentration, as well as increased number of dip coating cycles. Finally, vaccination of mice using microneedles stabilized by
trehalose generated strong antibody responses and provided full protection against high-dose lethal challenge
infection. In summary, this study provides detailed analysis to guide formulation of microneedle patches coated with
influenza VLP
vaccine and demonstrates effective vaccination in vivo using this system.