基于黑猩猩型腺病毒载体AdC68的新型狂犬病疫苗研究  

A novel rabies vaccine based on the chimpanzee adenoviral vector AdC68

作　　者：朱睿[1] 迟喻丹[2] 邓飞 蓝柯[2] 周东明[2] 

机构地区：[1]上海大学生命科学学院,200444 [2]中国科学院上海巴斯德研究所疫苗中心,200031 [3]四川省成都远睿生物技术有限公司,610213

出　　处：《中华微生物学和免疫学杂志》2016年第6期442-447,共6页Chinese Journal of Microbiology and Immunology

摘　　要：目的：探索一种基于复制缺陷型黑猩猩腺病毒载体的新型狂犬病疫苗AdC68-rab. gp的遗传稳定性、免疫应答及免疫保护效果。方法构建表达狂犬病病毒ERA株糖蛋白的重组腺病毒AdC68-rab. gp,通过酶切病毒基因组、病毒感染细胞、免疫小鼠、测定中和抗体滴度以及攻毒试验等研究AdC68-rab. gp的遗传稳定性和对小鼠的免疫保护效果。结果经过15次连续传代的重组腺病毒基因组稳定；单次免疫AdC68-rab. gp 4周,小鼠血清中可检测到高滴度的抗狂犬病病毒中和抗体；免疫6个月后,小鼠血清中的中和抗体滴度仍维持高水平；并且单次免疫小鼠100%拮抗致死剂量狂犬病病毒的攻击感染。结论新型狂犬病疫苗AdC68-rab. gp具有较好的遗传稳定性,并能诱导理想的免疫保护效果,具有很大的应用价值。Objective To investigate the genetic stability, immunogenicity and protective efficacy of AdC68-rab. gp, a novel rabies vaccine based on the replication-defective chimpanzee adenoviral vector AdC68-ept. Methods The recombinant adenovirus AdC68-rab. gp expressing the glycoprotein of rabies vi-rus ERA strain was constructed. Genomes of the AdC68-rab. gp of different generations were extracted and analyzed. HEK293 and Huh7 cells were infected with the AdC68-rab. gp of different generations. ICR mice were immunized with the AdC68-rab. gp and blood samples were collected 4 weeks or 6 months after immuni-zation. Rapid fluorescent focus inhibition test （ RFFIT） was performed to detect the neutralizing antibody against rabies virus in mice serum samples. ICR mice were challenged with lethal dose of rabies virus 4 weeks after the immunization with AdC68-rab. gp to evaluate the protective efficacy of AdC68-rab. gp. Re-sults The genome of AdC68-rab. gp was stable after 15 passages, which was identical to that of the 5th and 1st generations. High levels of neutralizing antibody against rabies virus in serum samples were detected in mice immunized with AdC68-rab. gp and maintained for a long period of time. Immunization mice with one dose of AdC68-rab. gp could protect all mice from the lethal dose challenge of rabies virus. Conclusion The novel AdC68-rab. gp was characterized by good genetic stability and ideal protective effi-cacy. The adenoviral vector based vaccine could be further developed as a potential candidate for the substi-tute of current rabies vaccine.

关 键 词：黑猩猩腺病毒载体 新型狂犬病疫苗 免疫应答 

分 类 号：R392[医药卫生—免疫学]