AA-PR8冷适应流感病毒疫苗株的制备及质量评价  

Preparation and quality evaluation of AA-PR8 cold-adapted influenza virus vaccine strain

作　　者：郭航炜 徐康维[1] 李星星 周瑞雪 谢莹 权娅茹[1] 赵慧[1] 李长贵[1] GUO Hang-wei;XU Kang-wei;LI Xing-xing;ZHOU Rui-xue;XIE Ying;QUAN Ya-ru;ZHAO Hui;LI Chang-gui(National Institutes for Food and Drug Control,NHC Key Laboratory of Research on Quality and Standardization of Biotech Products,NMPA Key Laboratory for Quality Research and Evaluation of Biological Products,Beijing 102629,China;不详)

机构地区：[1]中国食品药品检定研究院国家卫生健康委员会生物技术产品检定方法及其标准化重点实验室国家药品监督管理局生物制品质量研究与评价重点实验室,北京102629 [2]山西省食品药品检验所,山西太原030031

出　　处：《中国生物制品学杂志》2022年第8期912-917,共6页Chinese Journal of Biologicals

基　　金：北京市自然科学基金(L192009).

摘　　要：目的制备AA-PR8冷适应流感病毒疫苗株并进行质量评价。方法以A/Ann Arbor/6/60(H2N2)冷适应流感病毒PB2、PB1、PA、NP、M及NS 6个基因作为骨架,与PR8病毒HA、NA基因共同进行病毒拯救,制备AA-PR8冷适应流感病毒疫苗株,并评价其遗传稳定性、温度敏感性、冷适应表型以及在小鼠中的减毒特征。结果成功制备了AA-PR8冷适应流感病毒疫苗株,在鸡胚中传5代后,所有基因氨基酸位点均未发生突变。与PR8野病毒相比,AA-PR8疫苗株可在26℃条件下生长,不能在39℃条件下生长,具有温度敏感性及冷适应表型。与接种同等剂量的PR8野病毒的小鼠相比,接种AA-PR8疫苗株的小鼠体重降低幅度明显减小,未发生动物死亡;肺部病毒载量降低1000倍以上。结论成功制备了遗传稳定性好、具有温度敏感性及冷适应表型、小鼠致病能力弱的AA-PR8冷适应流感病毒疫苗株。Objective To prepare and evaluate the quality of AA-PR8 cold-adapted influenza virus vaccine strain.Methods PB2,PB1,PA,NP,M and NS genes of A/Ann Arbor/6/60(H2N2)cold-adapted influenza virus were served as skeleton for rescuing the virus cooperatively with HA and NA genes of PR8 virus.The prepared AA-PR8 coldadapted influenza virus vaccine strain was evaluated for genetic stability,temperature sensitivity,cold-adapted phenotype and attenuated characteristic in mice.Results AA-PR8 cold-adapted influenza virus vaccine strain was prepared successfully,which showed no mutation in amino acid sites of all genes after subculture to passage 6 in chick embryo.Compared with PR8 wild virus,AA-PR8 vaccine strain could grow at 26℃,while could not grow at 39℃,indicating the temperature sensitivity and cold-adapted phenotype.Compared with those of mice inoculated with PR8 wild virus at the same dosage,the weight loss of mice inoculated with AA-PR8 vaccine strain decreased significantly with no death,and the viral load in lungs decreased by more than 1000 folds.Conclusion AA-PR8 cold-adapted influenza virus vaccine strain was successfully prepared,which showed good genetic stability,temperature sensitivity,cold-adapted phenotype and low pathogenicity in mice.

关 键 词：冷适应 流感疫苗 反向遗传 

分 类 号：R183.3[医药卫生—流行病学] R392-3[医药卫生—公共卫生与预防医学]