Publications

Number of TRR60 publications/joint publications

total: 292 publications in Funding Period 1 + 2 (until December 2018)
thereof: 98 Sino-German joint publications (= 33%)

TRR60 list of publications

list of all TRR60 publications for download
(final version 31 December, 2018)
For further publications of the TRR60 members you may check the homepage of the Sino-German Virtual Institute for Viral Immunology www.uni-due.de/sgvivi

April 2018 Imaging of cytotoxic antiviral immunity

Lucas Otto, Gennadiy Zelinskyy, Marc Schuster, Ulf Dittmer, Matthias Gunzer

Imaging of cytotoxic antiviral immunity while considering the 3R principle of animal research

Journal of Molecular Medicine, April 2018, Volume 96, Issue 3-4

Abstract
Adoptive cell transfer approaches for antigen-specific CD8⁺ T cells are used widely to study their effector potential during infections or cancer. However, contemporary methodological adaptations regarding transferred cell numbers, advanced imaging, and the 3R principle of animal research have been largely omitted. Here, we introduce an improved cell transfer method that reduces the number of donor animals substantially and fulfills the requirements for intravital imaging under physiological conditions. For this, we analyzed the well-established Friend retrovirus (FV) mouse model. Donor mice that expressed a FV-specific T cell receptor (TCR^tg) and the fluorescent protein tdTomato were used as source of antigen-specific CD8⁺ T cells. Only a few drops of peripheral blood were sufficient to isolate ~ 150,000 naive reporter cells from which 1000 were adoptively transferred into recently FV-infected recipients. The cells became activated and functional and expanded strongly in the spleen and bone marrow within 10 days post infection. Transferred CD8⁺ T cells participated in the antiviral host response within a natural range and developed an effector phenotype indistinguishable from endogenous effector CD8⁺ T cells. Additionally, the generated reporter cell frequency allowed single cell visualization and tracking of a physiological antiretroviral CD8⁺ T cell response by intravital two-photon microscopy. Highly reproducible results were obtained in independent experiments by reusing the same donors repetitively for multiple transfers. Our approach allows a strong reduction of experimental animals required for studies on antigen-specific CD8⁺ T cell function and should be applicable to other transfer models.

June 2015 Nanoparticles for vaccination

Viktoriya Sokolova, Astrid Maria Westendorf, Jan Buer, Klaus Überla, Matthias Epple

The potential of nanoparticles for the immunization against viral infections (review)

Journal of Materials Chemistry B, 2015, 3, 4767 - 4779

Abstract
Vaccination has a great impact on the prevention and control of infectious diseases. However, there are still many infectious diseases for which an effective vaccine is missing. Thirty years after the discovery of the AIDS-pathogen (human immunodeficiency virus, HIV) and intensive research, there is still no protective immunity against the HIV infection. Over the past decade, nanoparticulate systems such as virus-like particles, liposomes, polymers and inorganic nanoparticles have received attention as potential delivery vehicles which can be loaded or functionalized with active biomolecules (antigens and adjuvants). Here we compare the properties of different nanoparticulate systems and assess their potential for the development of new vaccines against a range of viral infections.

February 2015 New outstanding publication by TRR60 Group C06N

Khairnar V, Duhan V, Maney SK, Honke N, Shaabani N, Pandyra AA, Seifert M, Pozdeev V, Xu HC, Sharma P, Baldin F, Marquardsen F, Merches K, Lang E, Kirschning C, Westendorf AM, Häussinger D, Lang F, Dittmer U, Küppers R, Recher M, Hardt C, Scheffrahn I, Beauchemin N, Göthert JR, Singer BB, Lang PA, Lang KS.

CEACAM1 induces B-cell survival and is essential for protective antiviral antibody production.

Nat Commun. 2015 Feb 18;6:6217.

Abstract
B cells are essential for antiviral immune defence because they produce neutralizing antibodies, present antigen and maintain the lymphoid architecture. Here we show that intrinsic signalling of CEACAM1 is essential for generating efficient B-cell responses. Although CEACAM1 exerts limited influence on the proliferation of B cells, expression of CEACAM1 induces survival of proliferating B cells via the BTK/Syk/NF-κB-axis. The absence of this signalling cascade in naive Ceacam1(-/-) mice limits the survival of B cells. During systemic infection with cytopathic vesicular stomatitis virus, Ceacam1(-/-) mice can barely induce neutralizing antibody responses and die early after infection. We find, therefore, that CEACAM1 is a crucial regulator of B-cell survival, influencing B-cell numbers and protective antiviral antibody responses.

Virologica Sinica February 2014

Virologica Sinica has dedicated its February 2014 issue to TRR60 topics. This is a special issue on "Chronic viral infections and immunomodulation" organized by PI Mengji Lu (Project B5), with the focus on the interactions of the host immune system with HBV, HCV and HIV. Editor-in-chief of Virologica Sinica is PI Xinwen Chen (A9N).

Selected high ranking TRR60 publications - FP1

Liu J, Zhang E, Ma Z, Wu W, Kosinska A, Zhang X, Möller I, Seiz P, Glebe D, Wang B, Yang D, Lu M, Roggendorf M.
Enhancing virus-specific immunity in vivo by combining therapeutic vaccination and PD-L1 blockade in chronic hepadnaviral infection.
PLoS Pathog. 2014 Jan;10(1):e1003856.

Dietze KK, Zelinskyy G, Liu J, Kretzmer F, Schimmer S, Dittmer U.
Combining regulatory T cell depletion and inhibitory receptor blockade improves reactivation of exhausted virus-specific CD8(+) T cells and efficiently reduces chronic retroviral loads.
PLoS Pathog. 2013 Dec;9(12):e1003798.

Chen J, Wu M, Zhang X, Zhang W, Zhang Z, Chen L, He J, Zheng Y, Chen C, Wang F, Hu Y, Zhou X, Wang C, Xu Y, Lu M, Yuan Z.
Hepatitis B virus polymerase impairs interferon-α-induced STATs activation through inhibition of importin-α5 and protein kinase C-δ
Hepatology 2013 57:470

Knuschke T, Sokolova V, Rotan O, Hansen W, Staeheli P, Epple M, Buer J, Westendorf AM.
Immunization with biodegradable nanoparticles efficiently induces cellular immunity and protects against influenza virus infection.
J Immunology 2013 190:6221

Kosinska AD, Zhang E, Johrden L, Liu J, Seiz PL, Zhang X, Ma Z, Kemper T, Fiedler M, Glebe D, Wildner O, Dittmer U, Lu M, Roggendorf M.
Combination of DNA prime - adenovirus boost immunization with entecavir elicits sustained control of chronic hepatitis B in the woodchuck model.
PLoS Pathogens 2013 9:e1003391

Li J, Liu K, Liu Y, Xu Y, Zhang F, Yang H, Liu J, Pan T, Chen J, Zhang X, Chen L, Zhang J, Zhang X, Zhang Z, and Yuan Z. Interferon induces cell-to-cell transfer of antiviral molecules via exosomes as an antiviral mechanism.
Nature Immunology 2013 14(8):793

Dietze KK, Zelinskyy G, Gibbert K, Schimmer S, Francois S, Myers L, Sparwasser T, Hasenkrug KJ, Dittmer U.
Transient depletion of regulatory T cells in transgenic mice reactivates virus-specific CD8+ T cells and reduces chronic retroviral setpoints.
Proc Natl Acad Sci USA. 2011 108:2420.

Ruhl M, Knuschke T, Schewior K, Glavinic L, Neumann-Haefelin C, Chang DI, Klein M, Heinemann FM, Tenckhoff H, Wiese M, Horn PA, Viazov S, Spengler U, Roggendorf M, Scherbaum N, Nattermann J, Hoffmann D, Timm J; East German HCV Study Group.
CD8+ T-cell response promotes evolution of hepatitis C virus nonstructural proteins.
Gastroenterology 2011 140:2064

Bröring R, Zhang X, Kottilil S, Trippler M, Jiang M, Lu M, Gerken G, Schlaak JF.
The interferon stimulated gene 15 functions as a proviral factor for the hepatitis C virus and as a regulator of the IFN response.
Gut 2010 59:1111

Zelinskyy G, Dietze KK, Hüsecken YP, Schimmer S, Nair S, Werner T, Gibbert K, Kershaw O, Gruber AD, Sparwasser T, Dittmer U.
The regulatory T cell response during acute retroviral infection is locally defined and controls the magnitude and duration of the virus-specific cytotoxic T cell response.
Blood 2009 114: 3199