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miragenews.com
Researchers at Technical University of Munich (TUM), Helmholtz Zentrum München and the German Center for Infection Research (DZIF) have developed a novel therapeutic approach to cure chronic hepatitis B. The scientists found that the large amount of hepatitis B virus proteins expressed in the liver prevents the body’s immune system to defeat the virus. Knocking down the expression of the virus’ proteins may enable a successful therapeutic vaccination.
Around 260 million humans, more than three percent of the world’s population, are chronically infected by the hepatitis B virus. As a result, every year, 880,000 people worldwide die of liver failure or hepatocellular carcinoma. Currently no curative therapy is available. The therapies available to date inhibit virus replication, but need to be given long-term. As long as infected people cannot form an adequate immune response, the virus will survive. This is precisely where Prof. Ulrike Protzer, head of the Institute of Virology at TUM and Helmholtz Zentrum München, and her team start.
Novel Therapeutic Approach
Successful Suppression of Virus Proteins in Mice
Consequently, the researchers first developed a method to suppress the hepatitis B virus proteins. They used siRNAs, small ribonucleic acid molecules that bind to the messenger RNA of the virus’ proteins. By labelling the messenger RNA with siRNA, the infected cell receives the signal that the viral RNA is undesired and removes it. However, the suppression of protein expression alone was not sufficient to reverse the inhibition of the CD8+ T-cells in chronically infected mice.
Infection Cured in Mice
The scientists therefore had to go one step further: “We then combined the siRNA method with a therapeutic vaccination developed by us. This enabled us to trigger a strong immune response against the virus. This led to cure of hepatitis B virus infection in two different mouse models,” explains Dr. Thomas Michler, researcher at TUM and one of the two first authors of the study.
Novel Therapeutic Vaccination Soon in a Clinical Trial
The newly developed vaccine, called TherVacB, will be tested as an immunotherapy in a two-year clinical trial starting in 2021. “The therapeutic vaccine we have developed is indeed very promising as it induces neutralizing antibodies and T-cell responses,” said Dr. Anna Kosinska, the other first author of the study. The vaccine will be administered in three doses every four weeks. It has been designed to target the majority of all hepatitis B viruses and therefore will be beneficial to most people infected worldwide.
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