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Kurzfassung

• Novel vaccination strategy against chronic liver diseases through stimulation of IMATEs with TLR9-L
• IMATEs are an anatomic compartment within the liver tissue consisting of myeloid cells
• iMATEs overcome regulatory cues that limit immune response during chronic liver infections

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Hintergrund

Immunotherapy of chronic hepatitis B is particularly difficult as the hepatic microenvironment is limiting local cytotoxic T lymphocyte (CTL) proliferation after infection. However, CTLs are an important element for overcoming chronic infections of the liver. So far only a prophylactic vaccination against hepatitis B virus is available and a protection post-infection by means of vaccination has not been possible to this point. Accordingly, there is a strong demand for new therapeutic options.

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Bilder & Videos

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Lösung

A so far unrecognized anatomic compartment within the liver tissue consisting of myeloid cells - called iMATEs (“intrahepatic myeloid-cell aggregates for T cell population expansion”) - can be exploited as a novel vaccination strategy against chronic viral liver infections. iMATEs overcome regulatory cues that limit immune response during chronic liver infections and support local CTL expansion by generation of cocoon-like structures. A dramatic expansion of CTLs in the liver can be achieved by targeted stimulation of iMATEs with TLR9-L as a prophylactic or therapeutic vaccine. The proof-of concept has been shown in vivo in mouse models.

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Vorteile

The present invention provides a convenient and reliable prophylactic as well as therapeutic vaccine strategy. The use of TLR9 agonists induces the formation of iMATEs, which generate a sufficient number of CTLs resulting in the overcoming of chronic viral infections.