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Author Notes:

Reprints or correspondence: Ioanna Skountzou, MD, PhD, Dept of Microbiology & Immunology and Emory Vaccine Center, Emory University School of Medicine, 1510 Clifton Rd, Atlanta, GA 30322 (iskount@emory.edu).

Potential conflicts of interest: Mark R. Prausnitz serves as a consultant and is an inventor on patents licensed to companies developing microneedle-based products. This possible conflict of interest has been disclosed and is being managed by Georgia Tech and Emory University. All other authors: no conflicts.

Presented in part: First International Conference on Microneedles, Atlanta, GA, 23–25 May 2010. 2nd Annual Georgia Nanotechnology in Infectious Diseases Symposium, Atlanta, GA, 1 April 2010.

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Research Funding:

The work was supported in part by the US National Institutes of Health (NIH; EB006369 and AI074579) and MdPM was supported by the National Institute of Allergy and Infectious Diseases, NIH (IPIRC contract 5 HHSN266200700006C).

Serological Memory and Long-term Protection to Novel H1N1 Influenza Virus After Skin Vaccination

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Journal Title:

Journal of Infectious Diseases

Volume:

Volume 204, Number 4

Publisher:

, Pages 582-591

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Background. A major goal in influenza vaccine development is induction of serological memory and cellular responses to confer long-term protection and limit virus spread after infection. Here, we investigate induction of long-lived immunity against the 2009 H1N1 virus after skin vaccination. Methods. BALB/c mice received a single dose of 5 μg inactivated A/California/04/09 virus via coated metal microneedles (MN) applied to skin or via subcutaneous injection. Results. MN or subcutaneous vaccination elicited similar serum IgG and hemagglutination inhibition titers and 100% protection against lethal viral challenge 6 weeks after vaccination. Six months after vaccination, the subcutaneous group exhibited a 60% decrease in functional antibody titers and extensive lung inflammation after challenge with 10 × LD50 of homologous virus. In contrast, the MN group maintained high functional antibody titers and IFN-γ levels, inhibition of viral replication, and no signs of lung inflammation after challenge. MN vaccination conferred complete protection against lethal challenge, whereas subcutaneous vaccination induced only partial protection. These findings were further supported by high numbers of bone marrow plasma cells and spleen antibody-secreting cells detected in the MN group. Conclusions. A single skin vaccination with MN induced potent long-lived immunity and improved protection against the 2009 H1N1 influenza virus, compared with subcutaneous injection.

Copyright information:

© 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

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