Around 50 million people worldwide have chronic hepatitis C virus (HCV) infections. This may lead to the development of severe liver diseases such as cirrhosis or liver cancer. New curative therapies have significantly improved the treatment options. However, these therapies are expensive and therefore often unavailable, especially in countries with high rates of infection. In addition, many people with HCV infection are unaware of their infection—it is estimated that only 20 percent of all infections worldwide are diagnosed. Moreover, a cure does not protect against reinfection with HCV. Despite the existing therapies, around 1.4 million people are newly infected with HCV every year. Therefore, the WHO’s goal of reducing the number of new HCV infections by 90 percent by 2030 will be almost impossible to achieve without a vaccine. In this context, a recent WHO international study on prioritisation of vaccine research and development also highlighted the importance of research into an HCV vaccine.
Understanding natural protection paves the way to hepatitis C vaccine development
A major challenge in the development of a hepatitis C vaccine is the enormous diversity of the virus. The diversity is essentially driven by a high error rate during viral genome replication, which constantly creates new virus variants—totaling up to an estimated trillion variants per infected person per day. We are working intensively on the development of a vaccine that generates protective immunity against as many virus variants as possible.
An important starting point is the observation that approximately 30 percent of people infected with HCV spontaneously eliminate the infection, i.e. develop an effective antiviral immune response. Neutralising antibodies play a particularly important role in self-limiting HCV infection. Several research groups could show that neutralising antibodies targeting highly conserved regions of the HCV envelope proteins are associated with a natural cure of the infection. The virus needs these parts of the envelope proteins to bind to host receptors. Therefore, these regions cannot change, are highly conserved and almost identical in all different HCV variants.
The DZIF scientists have developed an experimental system to precisely determine the efficacy of antibodies against many different HCV variants. Using this system, they have discovered some of the most potent antibodies and their target structures to date. Additionally, they are now evaluating the efficacy of vaccine candidates using this experimental system. Furthermore, they are building on the latest findings regarding the target structures of these special antibodies and developing DZIF-HCV vaccine candidates based on several vaccine platforms and through antigen optimisation.
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Literature
- Hasso-Agopsowicz M, Hwang A, Hollm-Delgado MG, Umbelino-Walker I, Karron RA, Rao R, Asante KP, Sheel M, Sparrow E, Giersing B. Identifying WHO global priority endemic pathogens for vaccine research and development (R&D) using multi-criteria decision analysis (MCDA): an objective of the Immunization Agenda 2030. EBioMedicine. 2024 Nov 4:105424. doi: 10.1016/j.ebiom.2024.105424. Epub ahead of print. PMID: 39500705.
