Adjuvanted Influenza Vaccine Administered Intradermally Elicits Robust Long-Term Immune Responses that Confer Protection from Lethal Challenge

• Type of Material: Article
• Authors: Maria del P. Martin, Emory University; Shaguna Seth, MDRNA, Inc.; Dimitrios G. Koutsonanos, Emory University; Joshy Jacob, Emory University; Richard W Compans, Emory University; Ioanna Skountzou, Emory University
• Language: English
• Date: 2010-05-28
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2010 Martin et al.
• License: Creative Commons Attribution 2.5 Generic
• Final Published Version (URL): http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0010897
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 5
• Issue: 5
• Start Page: 1
• End Page: 9
• Grant/Funding Information: This work was supported in part by National Institutes of Health grants A1074579 and by contract HHSN266200700006C from NIH/NIAID.; Maria del P. Martin is a trainee supported by contract HHSN266200700006C from NIH/NIAID.
• Research Categories: Health Sciences, Immunology; Biology, Microbiology

Abstract

Background The respiratory illnesses caused by influenza virus can be dramatically reduced by vaccination. The current trivalent inactivated influenza vaccine is effective in eliciting systemic virus-specific antibodies sufficient to control viral replication. However, influenza protection generated after parenteral immunization could be improved by the induction of mucosal immune responses. Methodology/Principal Findings Transcutaneous immunization, a non-invasive vaccine delivery method, was used to investigate the quality, duration and effectiveness of the immune responses induced in the presence of inactivated influenza virus co-administered with retinoic acid or oleic acid. We observed an increased migration of dendritic cells to the draining lymph nodes after dermal vaccination. Here we demonstrate that this route of vaccine delivery in combination with certain immunomodulators can induce potent immune responses that result in long-term protective immunity. Additionally, mice vaccinated with inactivated virus in combination with retinoic acid show an enhanced sIgA antibody response, increased number of antibody secreting cells in the mucosal tissues, and protection from a higher influenza lethal dose. Conclusions/Significance The present study demonstrates that transdermal administration of inactivated virus in combination with immunomodulators stimulates dendritic cell migration, results in long-lived systemic and mucosal responses that confer effective protective immunity.