title: Transdermal influenza immunization with vaccine-coated microneedle arrays.
abstract: BACKGROUND
  Influenza is a contagious disease caused by a pathogenic virus, with outbreaks all over the world and thousands of hospitalizations and deaths every year. Due to virus antigenic drift and short-lived immune responses, annual vaccination is required. However, vaccine coverage is incomplete, and improvement in immunization is needed. The objective of this study is to investigate a novel method for transdermal delivery using metal microneedle arrays (MN) coated with inactivated influenza virus to determine whether this route is a simpler and safer approach than the conventional immunization, capable to induce robust immune responses and confer protection against lethal virus challenge.
  
  
  RESULTS
  Inactivated A/Aichi/2/68 (H3N2) influenza virus was coated on metal microneedle arrays and applied to mice as a vaccine in the caudal dorsal skin area. Substantial antibody titers with hemagglutination inhibition activity were detected in sera collected two and four weeks after a single vaccine dose. Challenge studies in mice with 5 x LD(50) of mouse adapted Aichi virus demonstrated complete protection. Microneedle vaccination induced a broad spectrum of immune responses including CD4+ and CD8+ responses in the spleen and draining lymph node, a high frequency of antigen-secreting cells in the lung and induction of virus-specific memory B-cells. In addition, the use of MN showed a dose-sparing effect and a strong Th2 bias when compared to an intramuscular (IM) reference immunization.
  
  
  CONCLUSIONS
  The present results show that delivery of inactivated influenza virus through the skin using metal microneedle arrays induced strong humoral and cellular immune responses capable of conferring protection against virus challenge as efficiently as intramuscular immunization, which is the standard vaccination route. In view of the convenience of delivery and the potential for self-administration, vaccine-coated metal microneedles may provide a novel and highly effective immunization method.
authors.affiliation: Department of Microbiology & Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Dimitrios G
authors.initials: DG
authors.lastname: Koutsonanos
authors.forename: Maria
authors.initials: M
authors.lastname: del Pilar Martin
authors.forename: Vladimir G
authors.initials: VG
authors.lastname: Zarnitsyn
authors.forename: Sean P
authors.initials: SP
authors.lastname: Sullivan
authors.forename: Richard W
authors.initials: RW
authors.lastname: Compans
authors.forename: Mark R
authors.initials: MR
authors.lastname: Prausnitz
authors.forename: Ioanna
authors.initials: I
authors.lastname: Skountzou
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D004867:Equipment Design; D007111:Immunity, Cellular / Q000187:drug effects; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage*; D051379:Mice; D009339:Needles; D014611:Vaccination / Q000379:methods*
chemical_list: D007252:Influenza Vaccines