Immunity And Biodistribution Of Chimeric Hepatitis B Virus Core Protein Virus-like Nanoparticles

The virus-like particle is an excellent non-viral vector,has a conformation and immunogenicity similar to the virus,transports the substance encapsulated inside the particle to a specific location inside the cell for the purpose of prevention,diagnosis,treatment,and has good Biocompatibility.Hepatitis B virus core protein virus-like particle(HBc VLP)can be disassembled and self-assembled in different environments,with excellent biocompatibility and biodegradability,and can be used with genes.Engineering or chemical methods for functional modification are an excellent new nano drug carrier.However,the virus-like particle carrier is a polypeptide,which may be submitted to the T cell for recognition after being taken up by the antigen-presenting cells,and activates the macrophage,thereby causing a delayed type hypersensitivity reaction.In some published papers,HBc VLPs have been widely used in anti-tumor related research as small molecule drug carriers or immunogenicity.This paper aims to explore the immunogenicity of several HBc VLP-based genetically engineered virus-like particles,and to analyze the degree of humoral and cellular immunity caused by different chimeric and modified virus-like particles by antibody titer and flow cytometry.To analyze how to regulate its immunogenicity when used as a carrier by using external surface modified PEG or encapsulating adjuvant.Each protein material was labeled Cy5.5 and injected into the tail vein of mice,and the biodistribution of different chimeric HBc VLPs in the main organs and tissues of the body was observed.The experimental results show that genetic engineering in the main immune region of HBc VLP can significantly reduce the immunogenicity of virus-like particles.Different chimeric HBc VLPs reduce humoral and cellular immunity to different degrees,and the phenomenon of aggregation in the liver is also alleviated..Modifying PEG with a molecular weight of 5000 on the outer surface of VLP can also greatly reduce the immunogenicity of the material and extend its half-life in vivo.HBc VLPs contain CpG as an adjuvant to enhance immune effects and to metabolize faster in the body.The chimeric brain-targeting peptide TGN-HBc significantly increased the accumulation of protein materials in brain tissue,which fully proved that HBc VLPs can be used as a flexible virus-like particle vaccine or carrier in nanomedicine.