Chronic infections of the hepatitis B virus (HBV) and hepatitis D virus (HDV) are major causes of severe liver damage and liver cancer.
A vaccine against hepatitis B exists, but over 250 million people currently have chronic infections. The available treatment rarely leads to the complete disappearance of the infection, which means that the risk of liver damage remains. Current treatment for chronic hepatitis D infection only cures about a quarter of patients.
That is why researchers at Karolinska Institutet are developing a new type of treatment that will hopefully provide a lasting treatment response against both viruses.
The treatment consists of two components designed to affect the immune system in different ways. First, a DNA-based vaccine is administered that activates the production of neutralizing antibodies and T-cells against both viruses. Then, repeated doses of a protein-based vaccine are given to reinforce the activation of the immune system.
The now published study shows that the treatment can protect cultured cells against HBV and HDV infection. When the treatment was given to mice carrying parts of the hepatitis B and D virus, which resembles a chronic HBV infection, the animals produced the desired antibodies and T-cells at high levels.
Furthermore, antibodies from treated mice were able to protect mice carrying human liver cells against simultaneous infection with HBV and HDV. In addition, these antibodies were able to protect mice with chronic HBV infection against HDV infection. This is of particular importance because patients with chronic HBV infection are at risk of serious illness if infected with HDV.
“These are promising results,” says Matti Sällberg, one of the study’s two lead authors. “The study shows this is a viable route and encourages us to continue developing this treatment for use in humans. We are now optimizing the protein-based part to enable large-scale production to pharmaceutical standards, and then doing the final safety studies before we can apply for our first study with human subjects.”
Rani Burm, Panagiota Maravelia, Gustaf Ahlen, Sandra Ciesek, Noelia Caro Perez, Anna Pasetto, Stephan Urban, Freya Van Houtte, Lieven Verhoye, Heiner Wedemeyer, Magnus Johansson, Lars Frelin, Matti Sällberg, Philip Meuleman. Novel prime-boost immune-based therapy inhibiting both hepatitis B and D virus infections. Gut, 2022; gutjnl-2022-327216 DOI: 10.1136/gutjnl-2022-327216
Karolinska Institutet. “New treatment principle for chronic hepatitis B and D infections.” ScienceDaily. ScienceDaily, 26 August 2022. <www.sciencedaily.com/releases/2022/08/220826113326.htm>.
Photo by Olga Kononenko