Publikationsdatenbank

Targeted antigen delivery to dendritic cells elicits robust antiviral T cell-mediated immunity in the liver (2017)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Volckmar, Julia (WE 12)

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

Quelle

Scientific reports

Bandzählung: 7

Seiten: 43985

ISSN: 2045-2322

Sprache

Englisch

Verweise

DOI: 10.1038/srep43985

Pubmed: 28266658

Kontakt

Institut für Tierpathologie

Robert-von-Ostertag-Str. 15
14163 Berlin
+49 30 838 62450
pathologie@vetmed.fu-berlin.de

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.