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Sublingual vaccination with influenza virus protects mice

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  • Sublingual vaccination with influenza virus protects mice

    Published online before print January 28, 2008
    Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0708684105

    IMMUNOLOGY
    Sublingual vaccination with influenza virus protects mice against lethal viral infection
    Joo-Hye Song*,, Huan H. Nguyen, Nicolas Cuburu,?, Taisuke Horimoto||, Sung-Youl Ko*, Se-Ho Park, Cecil Czerkinsky, and Mi-Na Kweon*,**
    *Mucosal Immunology Section, Viral Immunology Section, Laboratory Science Division, International Vaccine Institute, Seoul 151-818, Korea; ?Institut National de la Sant? et de la Recherche M?dicale U721, Universit? de Nice-Sophia Antipolis, 06107 Nice, France; ||Division of Virology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan; and Laboratory of Molecular Immunology, School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Korea
    Edited by Roy Curtiss III, Arizona State University, Tempe, AZ, and approved December 12, 2007 (received for review September 13, 2007)

    Abstract
    We assessed whether the sublingual (s.l.) route would be an effective means of delivering vaccines against influenza virus in mice by using either formalin-inactivated or live influenza A/PR/8 virus (H1N1). Sublingual administration of inactivated influenza virus given on two occasions induced both systemic and mucosal antibody responses and conferred protection against a lethal intranasal (i.n.) challenge with influenza virus. Coadministration of a mucosal adjuvant (mCTA-LTB) enhanced these responses and resulted in complete protection against respiratory viral challenge. In addition, s.l. administration of formalin-inactivated A/PR/8 plus mCTA-LTB induced systemic expansion of IFN--secreting T cells and virus-specific cytotoxic T lymphocyte responses. Importantly, a single s.l. administration of live A/PR/8 virus was not pathogenic and induced protection mediated by both acquired and innate immunity. Moreover, s.l. administration of live A/PR/8 virus conferred heterosubtypic protection against respiratory challenge with H3N2 virus. Unlike the i.n. route, the A/PR/8 virus, whether live or inactivated, did not migrate to or replicate in the CNS after s.l. administration. Based on these promising findings, we propose that the s.l. mucosal route offers an attractive alternative to mucosal routes for administering influenza vaccines.

    intranasal | mucosal adjuvant | mucosal immunity | redirection | secretory IgA

    --------------------------------------------------------------------------------
    Footnotes
    Author contributions: J.-H.S., C.C., and M.-N.K. designed research; J.-H.S., H.H.N., and N.C. performed research; T.H. and S.-H.P. contributed new reagents/analytic tools; J.-H.S., analyzed data; and J.-H.S. and M.-N.K. wrote the paper.
    The authors declare no conflict of interest.
    This article is a PNAS Direct Submission.
    **To whom correspondence should be addressed. E-mail: mnkweon@ivi.int




    hat-tip tropical!
    http://novel-infectious-diseases.blogspot.com/
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