Immunotherapy to cure chronic hepatitis B virus infections

Design of effective synthetic long peptide (SLP)-based therapeutic capable of inducing an effective immune response against hepatitis B virus-infected cells by avoiding immune tolerance and viral resistance

The aim of this project was to contribute to the development of an immunotherapy for chronic hepatitis B to cure the disease and reduce patient risk to develop end-stage liver disease. In collaboration the consortium first explored which parts of viral proteins would be best targets for the immune system and then used this knowledge to design and synthetize antigenic long peptide fragments (which is the prime expertise of ISA pharmaceuticals) to compose a drug product. Resulting SLP designs were tested in the Erasmus MC lab for their ability to boost and/or trigger HBV directed meaningful immune responses in blood samples of chronic HBV patients.  

The targeted immunotherapy aimed for is highly needed as 250 million people worldwide (40,000 patients in the Netherlands) suffer from incurable chronic hepatitis B of which ~5% will develop liver cancer. Currently the only available medication to control the virus does not cure disease and needs to be taken life-long.    

ISA Pharmaceuticals has previously demonstrated that immunotherapy based on antigenic SLPs derived from human papilloma virus (HPV - ISA101b) was effective to cure chronic infection and also beneficial in combination with standard of care treatment of advanced stages of HPV-associated cancer. This project thoroughly explored from different angles which protein fragments of hepatitis B virus proteins should be used to compose a therapy eliciting effective immune responses in all chronic hepatitis B. They considered viral mutations, viral protein function and the recognition of the virus by the adaptive immune system in a patient population. 

Based on gathered information, the consortium designed and synthetised in total 17 SLPs and subjected these to a multi-step testing pipeline. This resulted in 9 SLPs deemed suitable to boost HBV directed immune responses in blood samples of many patients. These SLPs are now candidates for the composition of a novel cHBV immunotherapy. 

Unsuccessful clearance of hepatitis B virus in chronic patients leads to serious liver problems including liver cancer. Boosting and/or inducing T cell responses against multiple conserved viral antigens with Synthetic Long Peptide immunotherapy may offer a cure. Together Erasmus MC and ISA pharmaceuticals designed and validated the active ingredients.
Technology Readiness Level (TRL)
4 - 5
Time period
42 months