Hepatitis B virus (HBV) infection persists because the virus-specific immune response is dysfunctional. Therapeutic vaccines might be used to end immune tolerance to the virus in patients with chronic disease, but these have not been effective in patients.
Using a preclinical mouse model, the scientists found that proteins of the hepatitis B virus forestall that specific immune cells of the body, purported CD8+ T-cells become effective. Based on these findings, the researchers built up a novel therapeutic methodology: first, the expression levels of the virus proteins are wrecked, and afterward, the immune cells are initiated by therapeutic vaccination. Rather than traditional vaccinations, which expect to forestall diseases before the outbreak, such an effective vaccination aims to fix previously existing chronic diseases.
Using siRNAs, small ribonucleic acid molecules, scientists developed a method to suppress the hepatitis B virus proteins. The siRNAs molecules bind to the messenger RNA of the virus’ proteins. By labeling the messenger RNA with siRNA, the infected cell receives the signal that the viral RNA is undesired and removes it. In any case, the suppression of protein expression alone was not sufficient to reverse the inhibition of the CD8+ T-cells in chronically infected mice.
Scientists then moved one step further: They combined the siRNA method with a therapeutic vaccination developed by them.
Dr. Thomas Michler, a researcher at TUM and one of the two first authors of the study, said, “This enabled us to trigger a strong immune response against the virus. This led to the cure of hepatitis B virus infection in two different mouse models.”
Dr. Anna Kosinska, the other first author of the study, said, “The newly developed vaccine, called TherVacB, will be tested as 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. 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.”
The study is published in Gastroenterology.