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    Utilization of Fc receptors as a mucosal vaccine strategy against an intracellular bacterium, Francisella tularensis

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    Authors
    Rawool, Deepak B.
    Bitsaktsis, Constantine
    Li, Ying
    Gosselin, Diane R.
    Lin, Yili
    Kurkure, Nitin V.
    Metzger, Dennis W.
    Gosselin, Edmund J.
    UMass Chan Affiliations
    Program in Immunology and Virology
    Graduate School of Biomedical Sciences
    Document Type
    Journal Article
    Publication Date
    2008-04-09
    Keywords
    Administration, Intranasal; Animals; Antibodies, Bacterial; Bacterial Vaccines; Cytokines; Francisella tularensis; Immunity, Mucosal; Immunization, Secondary; Immunoglobulin A; Immunologic Memory; Inflammation; Interferon-gamma; Liver; Lung; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mucous Membrane; Receptors, Fc; Spleen; Tularemia; Vaccination
    Life Sciences
    Medicine and Health Sciences
    
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    Link to Full Text
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3787710/
    Abstract
    Numerous studies have demonstrated that targeting Ag to Fc receptors (FcR) on APCs can enhance humoral and cellular immunity. However, studies are lacking that examine both the use of FcR-targeting in generating immune protection against infectious agents and the use of FcRs in the induction of mucosal immunity. Francisella tularensis is a category A intracellular mucosal pathogen. Thus, intense efforts are underway to develop a vaccine against this organism. We hypothesized that protection against mucosal infection with F. tularensis would be significantly enhanced by targeting inactivated F. tularensis live vaccine strain (iFt) to FcRs at mucosal sites, via intranasal immunization with mAb-iFt complexes. These studies demonstrate for the first time that: 1) FcR-targeted immunogen enhances immunogen-specific IgA production and protection against subsequent infection in an IgA-dependent manner, 2) FcgammaR and neonatal FcR are crucial to this protection, and 3) inactivated F. tularensis, when targeted to FcRs, enhances protection against the highly virulent SchuS4 strain of F. tularensis, a category A biothreat agent. In summary, these studies show for the first time the use of FcRs as a highly effective vaccination strategy against a highly virulent mucosal intracellular pathogen.
    Source

    J Immunol. 2008 Apr 15;180(8):5548-57.

    DOI
    10.4049/jimmunol.180.8.5548
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/32924
    PubMed ID
    18390739
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    Link to Article in PubMed

    ae974a485f413a2113503eed53cd6c53
    10.4049/jimmunol.180.8.5548
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