Projects Translational Virology

The antibody-mediated immune response appears to be an important step in the immune defence of the virus. The virus has developed several mechanisms to evade this immune response. We are taking advantage of this and are currently analysing highly sensitive detection methods for HEV-specific antibodies and infection markers as well as their functional analysis using the cell culture system. The overall aim is to understand which factors determine a sufficient and protective antibody response to the virus.

In close cooperation with the team of Prof. T. Krey (University of Lübeck, Institute of Biochemistry, Germany), we are investigating to what extent human monoclonal antibodies represent a therapeutic option against the virus. In particular, the SARS-Cov-2 pandemic has shown that this strategy can be safe and effective. We are focusing on antibodies that are present in the blood of people who have survived HEV infection. The aim is to identify these antibodies, synthesise them and later use them as a therapy. The evaluation of the identified antibodies plays an important role with regard to their ability to prevent the virus from entering the cell (neutralisation). On the other hand, we would like to identify antibodies that bind and neutralise all subtypes of the virus (so-called genotypes). 

References:
International Liver Congress (ILC) 2021:
Poster OS-1062 Katja Dinkelborg, George Ssebyatika, Lucas Hüffner, Prossie Lindah Nankya, Luisa J. Ströh, Heiner Wedemeyer, Thomas Pietschmann, Thomas Krey, Patrick Behrendt. Identification and characterization of neutralizing human monoclonal antibodies against Hepatitis E virus. Journal of Hepatology 2021 vol. 75(2) | S201–S293.
International Liver Congress (ILC) 2022:
Poster THU339 Katja Dinkelborg, George Ssebyatika, Elina Muriel Guzmán, Prossie Lindah Nankya, Luisa J Ströh, Lucas Hueffner, Volker Kinast, Toni Luise Meister, Heiner Wedemeyer, Eike Steinmann, Thomas Pietschmann, Thomas Krey, Patrick Behrendt. A novel class of glycan-specific human monoclonal antibodies neutralizing the hepatitis E virus. Journal of Hepatology 2022 vol. 77(S1) | S119–S388 

Grants:
VW-Foundation, German Centre for Infection Research, Helmholtz-Initiative One Health

Infection with HEV is associated with extrahepatic manifestations such as neurologic complaints or renal function deterioration in some individuals. In addition, infections with genotypes 1 and 2 (prevalent primarily in Africa) can cause severe courses inpregnant women. So far, it is unclear whether these extrahepatic manifestations are caused by direct infection of the respective organ system (neurons, placental cells, renal cells) or are indirect. We are therefore using our cell culture generated virus to test for possible infection of different human cells derived from different organ systems. These studies will reveal whether direct infection of these organs with the virus is possible and have implications for monitoring HEV patients in the context of infection. 

References:
International Liver Congress (ILC) 2020:
Poster SAT358 Avista Wahid, Daniel Todt, Markus Cornberg, Benjamin Maasoumy, Birgit Bremer, Sven Pischke, Tobias Müller, Felix Piecha, Julia Benckert, Eike Steinmann, Ansgar W. Lohse, Svenja Hardtke, Michael P. Manns, Heiner Wedemeyer, Patrick Behrendt. Clinical and molecular characterization of the human kidney as extrahepatic site of hepatitis E virus infection Journal of Hepatology 2020 vol. 73 | S653–S915

Grants:
German Centre for Infection Research
 

The efficient cell culture system for HEV established at TWINCORE enables the analysis of different inactivation methods of the virus. We are currently using this to analyze the inactivation of the virus by commercially available hand disinfectants. The knowledge gained from this will significantly influence the hygienic measures that are taken in the event of an infection.