Fachbereich Veterinärmedizin



    Targeted Antigen Delivery to Dendritic Cells Elicits Robust Antiviral T cell-Mediated Immunity in the Liver (2017)

    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Volckmar, Julia
    Gereke, Marcus
    Ebensen, Thomas
    Riese, Peggy
    Philipsen, Lars
    Lienenklaus, Stefan
    Wohlleber, Dirk
    Klopfleisch, Robert (WE 12)
    Stegemann-Koniszewski, Sabine
    Müller, Andreas J
    Gruber, Achim D (WE 12)
    Knolle, Percy
    Guzman, Carlos A
    Bruder, Dunja
    Scientific reports; 7(Artikel-Nr.: 43985) — S. 1–14
    ISSN: 2045-2322
    DOI: 10.1038/srep43985
    Pubmed: 28266658
    Institut für Tierpathologie

    Robert-von-Ostertag-Str. 15
    Gebäude 12
    14163 Berlin
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    Abstract / Zusammenfassung

    Hepatotropic viruses such as hepatitis C virus cause life-threatening chronic liver infections in millions of people worldwide. Targeted in vivo antigen-delivery to cross-presenting dendritic cells (DCs) has proven to be extraordinarily efficient in stimulating antigen-specific T cell responses. To determine whether this approach would as well be suitable to induce local antiviral effector T cells in the liver we compared different vaccine formulations based on either the targeting of DEC-205 or TLR2/6 on cross-presenting DCs or formulations not involving in vivo DC targeting. As read-outs we used in vivo hepatotropic adenovirus challenge, histology and automated multidimensional fluorescence microscopy (MELC). We show that targeted in vivo antigen delivery to cross-presenting DCs is highly effective in inducing antiviral CTLs capable of eliminating virus-infected hepatocytes, while control vaccine formulation not involving DC targeting failed to induce immunity against hepatotropic virus. Moreover, we observed distinct patterns of CD8(+) T cell interaction with virus-infected and apoptotic hepatocytes in the two DC-targeting groups suggesting that the different vaccine formulations may stimulate distinct types of effector functions. Our findings represent an important step toward the future development of vaccines against hepatotropic viruses and the treatment of patients with hepatic virus infection after liver transplantation to avoid reinfection.