昆明医科大学学报2024,Vol.45Issue(5):16-22,7.DOI:10.12259/j.issn.2095-610X.S20240503
HPV16 E6、E7多表位DNA疫苗的构建及免疫效果评估
Evaluations of Immunogenicity and Efficacy of A Novel HPV16 E6 and E7 Multi-epitope DNA Vaccine
摘要
Abstract
Objective To construct and evaluate the specific CTL cell response induced by HPV16 E6 and E7 multi epitope DNA vaccines and their intervention effects on tumor growth so as to reveal their potential as candidate HPV therapeutic vaccines.Methods The CTL epitopes of human HLA-A*02:01,HLA-A*11:01,HLA-A*24:02 restriction and C57BL/6 mouse H-2b restriction were predicted by the MHC-I processing and MHC-I binding methods in the IEDB website,and then screened for co-presentation of both based on scoring as well as ELISPOT experiment.The predicted CTL epitopes obtained were constructed into a multi-epitope DNA vaccine(pVAX1-10P),and the immunological interventions were performed in the mice transplanted with TC-1 tumour cells from prophylactic and therapeutic strategies respectively,and the ability of pVAX1-10P to induce specific CTL responses was assessed by flow cytometry.Results Prediction and screening yielded 10 CTL antigenic epitopes co-presented by human and murine MHC molecules.ELISPOT results showed that each peptide in the experimental group induced the specific immune responses in mouse lymphocytes.The constructed multi-epitope DNA vaccine,pVAX1-10P,induced the specific cellular immunity and significantly inhibited the tumour growth in both prophylactic and therapeutic experiments.Conclusion The constructed HPV16 E6 and E7 multi-epitope DNA vaccine,pVAX1-10P can induce specific CTL response and inhibit the tumour growth,which is expected as a promising candidate of HPV therapeutic DNA vaccine.关键词
宫颈癌/人乳头瘤病毒16/E6蛋白/E7蛋白/多表位DNA疫苗Key words
Cervical cancer/Human papillomavirus 16/E6 protein/E7 protein/Multi-epitope DNA vaccine分类
医药卫生引用本文复制引用
崔湘杰,陶玉芬,朱兰芳,姚宇峰,史荔..HPV16 E6、E7多表位DNA疫苗的构建及免疫效果评估[J].昆明医科大学学报,2024,45(5):16-22,7.基金项目
中国医学科学院医学与健康科技创新工程基金资助项目(2021-I2M-1-004) (2021-I2M-1-004)
云南省重大科技专项基金资助项目(202002AA100009) (202002AA100009)