mRNA based expression of Hepatitis E specific neutralizing antibodies in liver cells as therapeutic option

Hepatitis E virus (HEV) is a non-enveloped single-stranded RNA virus and the most common cause of acute hepatitis in humans worldwide. Serological marker studies showed that 420.000 individuals in Germany become infected with HEV annually. Chronic HEV infections can arise in approximately 50% of infected immunosuppressed individuals. This can lead to rapid progression of liver fibrosis and cirrhosis with the ultimate need for liver transplantation. As no approved treatment for hepatitis E is currently available, there is an urgent need for effective antiviral therapeutics.

Neutralizing antibodies have been identified by analyzing memory B-cells from patients who have undergone HEV infection. These antibodies potently inhibit virus entry into the cell. The recent success of mRNA-based vaccines and therapeutic approaches has led to major innovations that have contributed to further development of mRNA vaccines and associated technologies. Previous studies in in vitro and in vivo models have shown that the expression of monoclonal antibodies can be induced by transfection of the corresponding mRNA into liver cells.

The aim of this project is to produce suitable mRNA to induce the most efficient production of anti-HEV specific antibodies in cell culture. For this purpose, we first established an mRNA production and transfection system by testing different signal peptides and 5’UTRs for protein expression levels. The sequences of the previously identified human monoclonal antibodies were inserted into the most efficient mRNA formulation. The production of functional antibodies in liver cell lines was confirmed by ELISA. Neutralization assays further confirmed the antiviral activity of the antibodies.

Publication History

Article published online:
18 January 2023