A protective role of murine langerin(+) cells in immune responses to cutaneous vaccination with microneedle patches

• Type of Material: Article
• Authors: Joanna A. Pulit-Penaloza, Emory University; Edward Esser, Emory University; Elena Vassilieva, Emory University; Jeong Woo Lee, Georgia Institute of Technolog; Misha T. Taherbhai, Emory University; Brian Pollack, Emory University; Mark Prausnitz, Emory University; Richard Compans, Emory University; Ioanna Skountzou, Emory University
• Language: English
• Date: 2014-08-18
• Publisher: Nature Publishing Group: Open Access Journals - Option C
• Publication Version: Final Published Version
• Copyright Statement: © 2014, Macmillan Publishers Limited. All rights reserved
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/srep06094
• Title of Journal or Parent Work: Scientific Reports
• ISSN: 2045-2322
• Volume: 4
• Start Page: 6094
• End Page: 6094
• Grant/Funding Information: The work was supported by U.S. National Institute of Health grant NIH EB012495. We thank Dahnide Taylor-Williams for valuable laboratory technical support and thank Derek O'Hagan, Sushma Kommareddy and their colleagues at Novartis Vaccines and Diagnostics for providing influenza vaccine.
• Keywords: INACTIVATED INFLUENZA-VIRUS; DERMAL DENDRITIC CELLS; ANTIGEN; MOUSE; T-CELLS; MULTIDISCIPLINARY SCIENCES; DELIVERY; IMMUNIZATION; IN-VIVO; Science & Technology; EPIDERMAL LANGERHANS CELLS; Science & Technology - Other Topics; SKIN; Multidisciplinary Sciences
• Research Categories: Biology, Microbiology; Health Sciences, Immunology

Abstract

Cutaneous vaccination with microneedle patches offers several advantages over more frequently used approaches for vaccine delivery, including improved protective immunity. However, the involvement of specific APC subsets and their contribution to the induction of immunity following cutaneous vaccine delivery is not well understood. A better understanding of the functions of individual APC subsets in the skin will allow us to target specific skin cell populations in order to further enhance vaccine efficacy. Here we use a Langerin-EGFP-DTR knock-in mouse model to determine the contribution of langerin+ subsets of skin APCs in the induction of adaptive immune responses following cutaneous microneedle delivery of influenza vaccine. Depletion of langerin + cells prior to vaccination resulted in substantial impairment of both Th1 and Th2 responses, and decreased post-challenge survival rates, in mice vaccinated cutaneously but not in those vaccinated via the intramuscular route or in non-depleted control mice. Our results indicate that langerin+ cells contribute significantly to the induction of protective immune responses following cutaneous vaccination with a subunit influenza vaccine.