title: Enhanced Stability of Inactivated Influenza Vaccine Encapsulated in Dissolving Microneedle Patches.
abstract: OBJECTIVE
  This study tested the hypothesis that encapsulation of influenza vaccine in microneedle patches increases vaccine stability during storage at elevated temperature.
  
  
  METHODS
  Whole inactivated influenza virus vaccine (A/Puerto Rico/8/34) was formulated into dissolving microneedle patches and vaccine stability was evaluated by in vitro and in vivo assays of antigenicity and immunogenicity after storage for up to 3 months at 4, 25, 37 and 45°C.
  
  
  RESULTS
  While liquid vaccine completely lost potency as determined by hemagglutination (HA) activity within 1-2 weeks outside of refrigeration, vaccine in microneedle patches lost 40-50% HA activity during or shortly after fabrication, but then had no significant additional loss of activity over 3 months of storage, independent of temperature. This level of stability required reduced humidity by packaging with desiccant, but was not affected by presence of oxygen. This finding was consistent with additional stability assays, including antigenicity of the vaccine measured by ELISA, virus particle morphological structure captured by transmission electron microscopy and protective immune responses by immunization of mice in vivo.
  
  
  CONCLUSIONS
  These data show that inactivated influenza vaccine encapsulated in dissolving microneedle patches has enhanced stability during extended storage at elevated temperatures.
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Georgia Technology and Emory University, Georgia Institute of Technology, Atlanta, Georgia, 30332, USA.
authors.forename: Leonard Y
authors.initials: LY
authors.lastname: Chu
authors.affiliation: Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, 30329, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Ye
authors.affiliation: Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, 30329, USA.
authors.forename: Ke
authors.initials: K
authors.lastname: Dong
authors.affiliation: Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, 30329, USA.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Compans
authors.affiliation: Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, 30329, USA.
authors.forename: Chinglai
authors.initials: C
authors.lastname: Yang
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Georgia Technology and Emory University, Georgia Institute of Technology, Atlanta, Georgia, 30332, USA. prausnitz@gatech.edu.|School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, 311 Ferst Drive, Atlanta, Georgia, 30332, USA. prausnitz@gatech.edu.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Prausnitz
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems; D004356:Drug Storage; D006358:Hot Temperature; D006801:Humans; D007114:Immunization; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology / Q000627:therapeutic use; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control; D051379:Mice; D009339:Needles; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D057968:Transdermal Patch; D015164:Vaccines, Inactivated / Q000008:administration & dosage* / Q000276:immunology / Q000627:therapeutic use
chemical_list: D007252:Influenza Vaccines; D015164:Vaccines, Inactivated
keywords: influenza vaccine immunogenicity; microneedle patch; thermostability; vaccine stability