HPV58 (Human Papilloma Virus) type therapeutic composite genetic vaccine and construction method thereof

Abstract

The invention discloses an HPV58 (Human Papilloma Virus) type therapeutic composite genetic vaccine and a construction method thereof. In the vaccine, an HPV58 type E6 / E7 fusion gene is used as a target antigen, and GM / B7 is used as an antigen adjuvant, wherein stop codes of HPV58 type E6 and E7 genes are removed from the HPV58 type E6 / E7 fusion gene; and meanwhile, amino acids of 50, 63 and 106 on E6 protein and the amino acids 24, 26 and 92 on E7 protein are mutated into glycines. The HPV58 type therapeutic composite genetic vaccine provided by the invention has high safety, strong immunity and an ideal anti-tumor effect, provides a better choice for treating cervical carcinoma and precancerous lesion related to the HPV58 type infection, and is particularly suitable for HPV58 type highly-infective cervical carcinoma patients in China and Asia.

Description

technical field [0001] The invention relates to the field of prevention and treatment of cervical cancer, in particular to a human papillomavirus type 58 (hereinafter referred to as HPV58) therapeutic compound gene vaccine and a construction method thereof. Background technique [0002] Cervical cancer is one of the common gynecological malignancies, and its incidence rate ranks second among female malignancies, second only to breast cancer. There are about 131,500 new cases of cervical cancer in my country every year, accounting for 28.8% of the total number of new cases of cervical cancer in the world, and about 50,000 patients die of cervical cancer every year, most of which are located in economically underdeveloped western regions such as Guangxi. At present, traditional methods such as surgery, radiotherapy, and chemotherapy are not effective for patients with advanced cervical cancer, and the 5-year survival rate is only 50%. Etiological studies of cervical cancer ha...

AI Technical Summary

Problems solved by technology

However, this type of vaccine has the following problems: since the L1 and L2 capsid proteins are not expressed in cervical cancer and precancerous lesion tissues, the above-mentioned vaccines can only be used to prevent HPV58 infection, but for cervical tissue that has already been infected or pathological changes Ineffective treatment

This type of vaccine has the following problems: Although E1 and E2 proteins are involved in the replication of virus episomes and the transcription of early viral genes, they may be good target antigens in the early stage of infection, but the expression levels of E1 and E2 proteins are very low so that they are difficult to be detected by the immune system. recognized, allowing the virus to escape

However, this type of vaccine has the following problems: because only the HPV58E7 gene is used as an antigen and the antigenicity of another important gene E6 is ignored, and there is no synergistic related adjuvant to break immune tolerance, so the effect of the vaccine needs to be improved

(2) No use of E6 and E7 fusion genes as target antigens

[0007] There are no related reports on the development of chimeric vaccines using HPV58L1 and L2 combined with E6 and E7 as target antigens

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