Until now, many chronic infections, which potentially cause organ damage due to long-lasting inflammation processes, have not been treatable by vaccination once the infection has taken hold. The findings were published in the current issue of “Nature Immunology”.
With the discovery and development of vaccines, modern medicine succeeded in combating infectious pathogens. “The disadvantage, however, is that vaccinations must be prophylactic, that is they must take place before the first contact with the pathogen,” said Professor Percy Knolle, who was previously director of the Institute of Molecular Medicine of the University of Bonn and is now director of the Institute of Molecular Immunology of TU München (TUM). Until now, post-infection protection by means of vaccination has not been possible for common chronic infections with hepatitis viruses. These infections can progress to chronic liver inflammation and cause organ damage, eventually leading to a dangerous liver cirrhosis or liver cancer.
Scientists of the University of Bonn, together with their colleagues at TUM and Helmholtz Zentrum München as well as other national and international institutes, have now made a promising discovery in animal models. “We have discovered a new vaccination principle that is effective even against chronic infections,” said Knolle. The international team of researchers has identified the liver as a place where T cells, which were originally activated in the lymph nodes, can proliferate rapidly. These immune cells then target already existing chronic infections. “This is an essential step to treat chronic infectious diseases such as hepatitis B,” said Professor Ulrike Protzer, director of the Institute of Virology (VIRO) at Helmholtz Zentrum München and TUM. “In many small spaces in the liver, which are formed by a specific population of immune cells, a single T cell gives rise to approximately 100 further cells within a very short time,” added Professor Heikenwälder, likewise from VIRO. This extraordinary proliferation of T cells in the liver is the basis for the effectiveness of the therapeutic vaccination strategy of the scientists.
“We have discovered a basic immunological principle which can be applied to various research areas,” said Knolle. The deciphering of the signaling pathway may enable the development of successful therapeutic vaccines against common chronic infections caused by hepatitis viruses or malaria parasites, and perhaps also against liver cancer. However, it will take several years before clinical trials can be launched, because all of the preliminary studies must first be completed.
Huang, L. et al. (2013). Intrahepatic myeloid-cell aggregates enable local proliferation of CD8+ T cells and successful immunotherapy against chronic viral liver infection, „Nature Immunology“, doi: 10.1038/ni.2573
Helmholtz Zentrum München, the German Research Center for Environmental Health, pursues the goal of developing personalized medicine, i.e. a customized approach to the diagnosis, treatment and prevention of widespread diseases such as diabetes mellitus and lung disease. To that end, it investigates the interaction of genetics, environmental factors and lifestyle. The head office of the center is located in Neuherberg in the north of Munich. Helmholtz Zentrum München has a staff of approximately 2100 people and is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with some 34,000 staff members. www.helmholtz-muenchen.de
The Institute of Virology (VIRO) investigates viruses that chronically infect humans and can cause life-threatening diseases. The research activities of the institute focus mainly on the HI virus which causes AIDS, on endogenous retroviruses, which are integrated into our germline, and hepatitis B and C viruses, which cause liver cirrhosis and hepatocellular carcinoma. Molecular studies identify new diagnostic and therapeutic concepts to prevent and treat these viral diseases or to prevent the formation of virus-induced tumors.
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Department of Communication, Helmholtz Zentrum München – German Research Center for Environmental Health (GmbH), Ingolstädter Landstraße 1 85764 Neuherberg, Germany – Phone: +49(0)89-3187-2238 – Fax: +49(0)89-3187-3324 – email: presse(at)helmholtz-muenchen.de
Prof. Ulrike Protzer, Helmholtz Zentrum München – German Center for Environmental Research (GmbH), Institute of Virology, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany – Phone: +49(0)89-3187-3004 – email: protzer(at)helmholtz-muenchen.de