人乳头瘤病毒18型融合蛋白和重组痘苗病毒联合免疫的效果评价  

Combined immunization with human papillomavirus type 18 fusion protein and recombinant vaccinia virus in mice

作　　者：赵莉[1] 任皎[1] 冯靖 庞正[1] 黄盼盼 赵颖 谭文杰[1] 阮力[1] 田厚文[1] Zhao Li;Ren Jiao;Feng Jing;Pang Zheng;Huang Panpan;Zhao Ying;Tan Wenjie;Ruan Li;Tian Houwen(Key Laboratory of Medical Virology and Viral Disease,Ministry of Health,National Institute for Viral Disease Control and Prevention,Chinese Center for Disease Control and Prevention,Beijing 102206,China;National Vaccine and Serum Institute,Beijing 100176,China)

机构地区：[1]中国疾病预防控制中心病毒病预防控制所卫生部医学病毒和病毒病重点实验室,北京102206 [2]北京生物制品研究所有限责任公司,100176

出　　处：《中华实验和临床病毒学杂志》2018年第4期347-351,共5页Chinese Journal of Experimental and Clinical Virology

基　　金：国家高技术研究发展计划（863计划）（2012AA02A407）

摘　　要：目的研究人乳头状瘤病毒18型（HPV18）融合蛋白和重组痘苗病毒联合免疫诱发小鼠产生的细胞免疫和体液免疫反应水平。 方法原核表达系统表达并纯化的HPV18L231-600E7E6融合蛋白与表达HPV18E7E6融合蛋白的重组痘苗病毒（rVV18E7E6）联合免疫C57BL/6小鼠，通过酶联免疫斑点法（ELISPOT）、ELISA和假病毒中和实验分别对不同免疫程序的免疫组诱发机体产生的细胞免疫和体液免疫应答进行评价。结果HPV18L231-600E7E6融合蛋白/CpG佐剂初免、重组痘苗病毒rVV18E7E6加强免疫的联合免疫方式可以诱发小鼠产生最强水平的T细胞免疫反应，同时可产生较高水平的结合抗体，并能检测到低水平中和抗体。结论以HPV18L231-600E7E6/CpG初免、重组痘苗病毒rVV18E7E6加强免疫的联合免疫策略诱导了较强的细胞免疫和体液免疫应答，可作为治疗HPV18型慢性感染和宫颈癌手术后辅助治疗的候选疫苗。ObjectiveTo investigate the cellular and humoral immune responses induced by combined immunization with the fusion protein of human papillomavirus type 18 （HPV18） and the recombinant vaccinia virus.MethodsPurified HPV18L231-600E7E6 fusion protein, expressed by prokaryotic expression system, were immunized in combination with the recombinant vaccinia virus vaccine expressing HPV18E7E6 fusion protein （rVV18E7E6） by using various prime-boost regiments in C57BL/6 mice. Cellular and humoral immune responses were analyzed by enzyme-linked immunospot assay （ELISPOT）, enzyme-linked immunosorbent assay （ELISA）, and pseudovirus neutralization assay.ResultsHigher levels of cellular immune responses were induced in mice primed with the HPV18L231-600E7E6 fusion protein/adjuvant CpG and boosted with the recombinant vaccinia virus rVV18E7E6, than in other immunized mice. Higher binding antibody level was induced, and low level neutralizing antibody against pseudovirus was detected simultaneously.ConclusionsPriming with HPV18L231-600E7E6 fusion protein/CpG and boosting with the recombinant vaccinia virus rVV18E7E6 could induce higher cellular and humoral immune response in immunized mice, which might be taken as vaccine candidate for treatment of HPV18 chronic infection and postoperative adjuvant treatment for cervical cancer.

关 键 词：人乳头瘤病毒 宫颈肿瘤 疫苗 免疫治疗 

分 类 号：R186[医药卫生—流行病学] R737.33[医药卫生—公共卫生与预防医学]