New Vaccine Platform for Vaccination against Hepatitis B
A research team at the Paul-Ehrlich-Institut has developed a vaccine platform that induces a comprehensive immune response – and can be used as the basis for vaccines against novel pathogens.
Around 257 million people worldwide suffer from chronic liver inflammation caused by the hepatitis B virus (HBV). HBV not only causes liver inflammation, but also cirrhosis of the liver and liver cancer. In many cases, the development of the chronic infection is caused by an inadequate cellular immune defence by T cells. In the vaccines against hepatitis B which have been authorised to date, the protective effect is based primarily on the B cell response, the formation of protective antibodies.
New vaccine concepts should therefore induce a broader immune response. Scientists led by Prof. Eberhard Hildt, head of the Virology division, have conducted research into an HBV-VLP vaccine platform, which is based on virus-like particles (VLPs) of the hepatitis B virus. Specifically, the platform is a modified capsid – a regular structure made of proteins that serves to encapsulate the virus genome. Fusing the capsid with a TLM (translocation motif) peptide enables the VLPs to pass through cell membranes. Additional modifications allowed the research team to insert a loading site for the antigen against which immune protection is to be developed.
This vaccine platform has the potential to induce an effective immune response, both via the formation of antibodies and via the cellular immune response – and to make syringe-free vaccination possible.
Prof. Eberhard Hildt , Head of the Virology Division
Using in vitro and in vivo methods (mouse model), the researchers could observe that the antigen passes through the membranes into the cells and spreads throughout the whole organism. To test its efficacy in the animal model, the capsid was loaded with a surface antigen of the hepatitis B virus. The vaccine proved to be highly effective in the mouse model: the mice developed protective antibodies and a specific T cell immune response which led to the destruction of HBV-positive cells. This response could be particularly relevant in the development of a therapy for chronic infections. As the vaccine candidate can pass through membranes, it could be administered without a syringe – i.e. orally or transdermally using a patch.
The result is that a vaccine platform is now ready for further development. When loaded with antigens of other pathogens, it could contribute to the rapid development of vaccines against novel pathogens.
Funding
German Centre for Infection Research (DZIF)
Literature
Zahn T, Akhras S, Spengler C, Murra RO, Holzhauser T, Hildt E (2020): A new approach for therapeutic vaccination against chronic HBV infections.
Vaccine 38: 3105-3120.