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Description
Despite massive vaccination programmes, Hepatitis B Virus (HBV) remains the major cause of liver diseases. Therefore, more effective but at the same time economically feasible and commonly available preventive vaccines and CHB therapeutic vaccines, are particularly welcome. Commonly used, yeast-produced 2nd-generation preventive vaccines are based on the small surface antigen (S-HBsAg). More effective are the 3rd-generation vaccines containing also the medium and/or large surface antigens (M/L-HBsAg). Yet, they are produced in costly mammalian cells, thus their use is limited. The main component of tested CHB therapeutic vaccines is the core antigen (HBcAg), inducing strong Th1 response - mostly cellular type, which can be supplemented with HBsAgs or their immunodominant domains - inducers of Th2 response - humoral type. Virus-Like Particles (VLPs) VLPs based on HBcAg are well- characterized potential vaccine templates. Antigens or their fragments (epitopes) loaded on the surface of VLPs are therefore presented in a highly ordered structure, thus effectively for the immune system. VLP-assembled plant-derived antigens are considered alternative vaccines, due to low cost, biosafety, bioactivity, and possibility of oral immunisation. Immunogenicity of plant-produced S-HBsAg or HBcAg has been already proved. Both antigens, when used in injection immunization or that comprising injection priming and oral boosting, induced significant response of proper polarization. These results indicate that key epitopes of both antigens, combined in one type of chimeric VLPs, can induce the immune response of mixed Th1/Th2 polarization, required for CHB therapy. The main goal of this project is the development and the determination of immunogenicity of novel types of chimeric VLPs - formed by plant-produced HBcAg displaying key HBsAg epitopes: aSHBs and ΔpreS1 as well as TransLocation Motif (TLM) – enhancing permeability and immunogenicity of VLPs.