Preventing severe courses: new antibodies against hepatitis E
First author and former DZIF Academy fellow Katja Dinkelborg in the laboratory.
Infections with the hepatitis E virus often go unnoticed because they cause no symptoms. However, in patients with weakened immune systems or pre-existing liver damage, and in pregnant women, the virus can cause severe, potentially life-threatening liver inflammation. Despite existing therapeutic approaches, there are currently no authorized specific treatment options. Researchers at the German Center for Infection Research (DZIF) at TWINCORE, Centre for Experimental and Clinical Infection Research in Hannover, at the University of Lübeck, and at the University Hospital of Heidelberg have identified neutralizing antibodies that could be used therapeutically to prevent severe cases. The results of this research, which also involved other institutions and scientists, have been published in the journal Nature Communications.
The World Health Organization (WHO) estimates that approximately 20 million people worldwide are infected with HEV each year. Most cases are asymptomatic, but about 3.3 million develop symptomatic hepatitis, which can lead to severe chronic inflammation of the liver, including fibrosis or cirrhosis. In 2015, 44,000 people died as a result. In Germany, an estimated 400,000 people are infected each year, with some risk groups such as organ transplant recipients or people with liver damage at increased risk of severe disease.
"In our search for new therapeutic options, we examined which antibodies against the hepatitis E virus are formed in people who have survived the infection," says DZIF scientist Dr. Patrick Behrendt, Head of the Clinical Junior Research Group "Translational Virology" at TWINCORE and Senior Physician at the Department of Gastroenterology at the Hannover Medical School. To do this, they isolated so-called memory B cells from the blood of the cured patients. These are immune cells that produce antibodies. "During the more detailed characterization, we initially found that many of the antibodies were directed against the HEV capsid." This protein is a structural component of the virus that encloses its genetic information within infectious particles. However, it is also present as a soluble protein freely circulating in the blood of patients. "In this way, HEV redirects the immune response away from the infectious virus particles, thus escaping the immune response," says Behrendt.
This soluble capsid protein differs from the protein embedded in infectious viral particles by a specific modification that can potentially be used for new therapeutic approaches. "We then focused on the antibodies that specifically recognize infectious particles," says Dr. Katja Dinkelborg, a physician and researcher in Behrendt's group and one of the first authors of the publication.
Researchers at the University of Lübeck were able to decipher the exact structure and mode of action of these antibodies. Together with the team led by DZIF scientist Prof. Thomas Krey from the Institute of Biochemistry, they studied the antibodies in detail and were able to show how they bind to the virus and neutralize it. These findings are an important step towards a targeted antibody therapy against HEV. Behrendt and Krey now plan to further develop the neutralizing antibodies with antiviral activity in order to optimize them for clinical use. "Our results show that custom-designed antibodies are a promising approach to better treat hepatitis E infections," explains Krey. "With our research at the DZIF, we are laying the groundwork for future clinical trials and hope to make these antibodies available as a treatment option for at-risk groups in the near future."
Source: Press releases from TWINCORE, Centre for Experimental and Clinical Infection Research and the University of Lübeck
