Epstein-Barr virus (Epstein-Barr virus), also known as human herpesvirus type 4, has an infection rate of over 90% in the population. The global disease burden caused by EBV infection is enormous, and it was one of the first human cancer viruses to be identified. Prophylactic EBV vaccines have the potential to significantly reduce the incidence or severity of EBV-associated diseases. Epstein-Barr virus is associated with a variety of tumors of epithelial and lymphoid origin, such as Burkitt's lymphoma, Hodgkin's lymphoma, nasopharyngeal carcinoma of epithelial origin, and some gastric cancers.

Vaccination is the most effective way to prevent EBV infection. In 1973, Epstein and Achong first proposed the basic principle of developing a vaccine against Epstein-Barr virus. However, more than 40 years later, there is still no approved EBV vaccine. Therefore, it is urgent to develop new drugs for the treatment of EBV. EBV usually lurks in human normal epithelial cells and B lymphocytes, shuttles between B lymphocytes and epithelial cells, and spreads continuously in the human body\[2\], leading to the recurrence of malignant tumors such as nasopharyngeal carcinoma, gastric cancer, and lymphoma with transfer. It can be seen that the development of therapeutic drugs that directly target EBV is expected to achieve better therapeutic effects on EBV-related malignant tumors. At present, new biological treatment strategies targeting EBV have shown good therapeutic potential in nasopharyngeal carcinoma, infectious mononucleosis, lymphoma and other EBV-related diseases in the clinical trial stage, including viral vector vaccines, DC or CAR -T cell therapy. At present, the virus vector preparations targeting EBV include Ankara vaccinia virus and adenovirus. These viruses have safety risks of integrating into the host genome and causing genome mutations in patients. The DC (Dendritic cell) or CAR-T cell therapy strategy targeting EBV is complicated to operate, takes a long time, is difficult to control quality, is difficult to produce on a large scale, and has high production costs. In conclusion, the design strategy of the above-mentioned new biological therapy still has a high risk of difficult clinical or market transformation; therefore, it is necessary to develop new therapeutic biological agents targeting EBV.

mRNA vaccines are a promising new approach to cancer. Its working principle is: introduce the mRNA encoding the antigen into the cells of the body (especially the antigen-presenting cells), synthesize the antigen protein or polypeptide through the expression system of the host cell, activate cellular immunity and humoral immunity, and achieve the purpose of highly effective anticancer\[ 13\]. The mRNA does not need to enter the nucleus, it can be translated in the cytoplasm, and the effect is rapid; there is no risk of integration into the host genome, and it will be automatically degraded in the body, which is safe. Compared with traditional protein/polypeptide preparations, mRNA nucleic acid has no problems such as antigen conformation change and degradation, and has the advantages of long-term expression and persistent presentation of antigen; at the same time, it can simulate the natural infection process of the virus to activate the immune system and stimulate more Strong immune response; in addition, the production of mRNA preparations is simple and the synthesis is fast. Different mRNA preparations can be prepared using the same production steps and facilities, saving production costs. It is considered to be a new type of nucleic acid preparation with good clinical application prospects.

Based on the previous work, this project intends to carry out the research on new immunotherapy technology of "targeting EB virus mRNA nucleic acid to treat EBV-related malignant tumors". At present, there is no similar treatment method or product report in the world, which is very innovative and advanced. Therefore, this project intends to carry out phase I clinical research on the basis of previous research, in order to obtain a therapeutic candidate vaccine targeting EBV with independent intellectual property rights.