Transdermal Influenza Immunization with Vaccine-Coated Microneedle Arrays

• Type of Material: Article
• Authors: Dimitrios G. Koutsonanos, Emory University; Maria del Pilar Martin, Emory University; Vladimir G. Zarnitsyn, Georgia Institute of Technology; Sean P. Sullivan, Georgia Institute of Technology; Richard W Compans, Emory University; Mark R. Prausnitz, Georgia Institute of Technology; Ioanna Skountzou, Emory University
• Language: English
• Date: 2009
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: Copyright Koutsonanos et al.
• License: Creative Commons Attribution 3.0 Unported
• Final Published Version (URL): http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0004773
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 4
• Issue: 3
• Start Page: e4773
• End Page: e4773
• Grant/Funding Information: This work was supported in part by the National Institutes of Health grants AI074579 and EB006369 and carried out in part at the Center for Drug Design, Development and Delivery and the Institute for Bioengineering and Bioscience at Georgia Tech.
• Research Categories: Health Sciences, Immunology; Biology, Microbiology

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. Methodology/Principal Findings 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×LD50 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/Significance 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.