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  • 4/23/2013

Scientists deciphered mechanism

New Immunotherapy Approach to Treat Chronic Infections

A team of scientists from the Technische Universität München, Helmholtz Zentrum München and University of Bonn has deciphered a mechanism that in the future may enable therapeutic vaccination against chronic infections. 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”.

The expansion of T cells (green) occurs in cocoon-like structures in the liver. Monocytes (red) support the T cell expansion.
The expansion of T cells (green) occurs in cocoon-like structures in the liver. Monocytes (red) support the T cell expansion. (Photo: Uni Bonn)

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, 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 TUM and Helmholtz Zentrum München, together with their colleagues at the University of Bonn 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.


Publication: Intrahepatic myeloid cell-aggregates enable local CD8+ T cell proliferation and successful immunotherapy against chronic viral liver infection, „Nature Immunology“, DOI: 10.1038/ni.2573

Contact:
Prof. Dr. Percy A. Knolle
Technische Universität München
Klinikum rechts der Isar
Institute of Molecular Immunology
T: +49 89 4140 6920
E: percy.knolle@tum.de

Prof. Dr. Mathias Heikenwälder, Prof. Dr. Ulrike Protzer
Technische Universität München / Helmholtz Zentrum München
Institute of Virology (VIRO)
T: +49 89 4140 6886
E: protzer@tum.de; heikenwaelder@helmholtz-muenchen.de



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