Formulation of Microneedles Coated with Influenza Virus-like Particle Vaccine
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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.
KEY WORDScoating formulation influenza intradermal immunization microneedle virus-like particle vaccine
This work was supported in part by NIH grants R01-EB006369 (M.R.P.) and U01-AI0680003 (R.W.C.), SERCEB (R.W.C) and the Georgia Research Alliance Program grant (S.M.K). We thank Dr. Vladimir Zarnitsyn for microneedle fabrication, Dr Young-Bin Choy for SEM imaging, and Dr. Mark Allen for use of laser microfabrication facilities. M.R.P. serves as a consultant and is an inventor on patents licensed to companies developing microneedle-based products. These possible conflicts of interest have been disclosed and are being managed by Georgia Tech and Emory University.
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