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

2.50
Hdl Handle:
http://hdl.handle.net/10033/621216
Title:
Targeted antigen delivery to dendritic cells elicits robust antiviral T cell-mediated immunity in the liver.
Authors:
Volckmar, Julia; Gereke, Marcus; Ebensen, Thomas; Riese, Peggy ( 0000-0001-6796-6780 ) ; Philipsen, Lars; Lienenklaus, Stefan ( 0000-0003-4790-3445 ) ; Wohlleber, Dirk; Klopfleisch, Robert; Stegemann-Koniszewski, Sabine; Müller, Andreas J; Gruber, Achim D; Knolle, Percy; Guzman, Carlos A; Bruder, Dunja ( 0000-0003-3066-189X )
Abstract:
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.
Affiliation:
Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr.7, 38124 Braunschweig, Germany.
Citation:
Targeted antigen delivery to dendritic cells elicits robust antiviral T cell-mediated immunity in the liver. 2017, 7:43985 Sci Rep
Journal:
Scientific reports
Issue Date:
7-Mar-2017
URI:
http://hdl.handle.net/10033/621216
DOI:
10.1038/srep43985
PubMed ID:
28266658
Type:
Article
Language:
en
ISSN:
2045-2322
Appears in Collections:
publications of the research group intravital microscopy in infection and immunity (INMI); publications of the research group vaccinology and applied microbiology (VAC); publications of the research group immunoregulation (IREG); publications of the department of experimental infection research ([TC] EXPI)

Full metadata record

DC FieldValue Language
dc.contributor.authorVolckmar, Juliaen
dc.contributor.authorGereke, Marcusen
dc.contributor.authorEbensen, Thomasen
dc.contributor.authorRiese, Peggyen
dc.contributor.authorPhilipsen, Larsen
dc.contributor.authorLienenklaus, Stefanen
dc.contributor.authorWohlleber, Dirken
dc.contributor.authorKlopfleisch, Roberten
dc.contributor.authorStegemann-Koniszewski, Sabineen
dc.contributor.authorMüller, Andreas Jen
dc.contributor.authorGruber, Achim Den
dc.contributor.authorKnolle, Percyen
dc.contributor.authorGuzman, Carlos Aen
dc.contributor.authorBruder, Dunjaen
dc.date.accessioned2018-01-02T13:05:22Z-
dc.date.available2018-01-02T13:05:22Z-
dc.date.issued2017-03-07-
dc.identifier.citationTargeted antigen delivery to dendritic cells elicits robust antiviral T cell-mediated immunity in the liver. 2017, 7:43985 Sci Repen
dc.identifier.issn2045-2322-
dc.identifier.pmid28266658-
dc.identifier.doi10.1038/srep43985-
dc.identifier.urihttp://hdl.handle.net/10033/621216-
dc.description.abstractHepatotropic 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.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleTargeted antigen delivery to dendritic cells elicits robust antiviral T cell-mediated immunity in the liver.en
dc.typeArticleen
dc.contributor.departmentHelmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr.7, 38124 Braunschweig, Germany.en
dc.identifier.journalScientific reportsen
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