AA-PR8冷适应流感病毒疫苗株在小鼠中的保护作用  

Protective effect of cold-adapted influenza virus vaccine strain AA-PR8 in mice

作　　者：徐康维[1] 郭航炜 李星星 谢莹 权娅茹[1] 赵慧[1] 李长贵[1] XU Kang-wei;GUO Hang-wei;LI Xing-xing;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)

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

出　　处：《中国生物制品学杂志》2022年第9期1040-1044,共5页Chinese Journal of Biologicals

基　　金：北京市自然科学基金(L192009)。

摘　　要：目的将AA-PR8冷适应流感病毒疫苗株免疫小鼠,检测小鼠IgG和IgA抗体产生情况,并对免疫后小鼠进行PR8流感病毒攻击,评价其保护效果。方法用AA-PR8冷适应流感病毒疫苗株滴鼻免疫小鼠2次,免疫间隔21 d,分别于第1次免疫后0、7、14、21、28、35和42 d采集小鼠血清和肺泡灌洗液,间接ELISA法检测IgG和IgA抗体效价。对采用1次免疫或0、14 d 2次免疫程序的小鼠进行5倍半数致死剂量的PR8流感病毒攻击,观察攻击后小鼠死亡情况及体重变化,攻击后第3天取小鼠肺脏,检测病毒载量。结果小鼠第1次免疫后7、14和21 d,血清IgG抗体GMT分别为152、230和264,肺泡灌洗液IgA抗体GMT分别为23、211和92;第2次免疫后7、14和21 d,血清IgG抗体GMT分别为348、919和1056,肺泡灌洗液IgA抗体GMT分别为53、368和160。免疫1次后14 d进行攻击,小鼠保护率为83.33%(5/6),体重降低幅度减少,肺脏病毒载量显著降低;0、14 d免疫2次后14 d进行攻击,小鼠保护率为100%(6/6),体重基本不降低,肺脏未检测到病毒。结论AA-PR8冷适应流感病毒疫苗株在小鼠中具有良好的免疫原性,显著降低小鼠AA-PR8流感病毒攻击后的肺脏病毒载量,提高了生存率。Objective To determine IgG and IgA antibodies in mice immunized with cold-adapted influenza virus vaccine strain AA-PR8,and challenge the immunized mice with PR8 influenza virus to evaluate the protective effect.Methods Mice were intranasally immunized with cold-adapted influenza virus vaccine strain AA-PR8 twice at an interval of 21 d,of which the serum and alveolar lavage fluid samples were collected 0,7,14,21,28,35 and 42 d after the first dose and determined for IgG and IgA antibody titers by indirect ELISA.Mice immunized with a single dose or two doses at an interval of 14 d were challenged with 5 times of the median lethal dose of PR8 influenza virus,and observed for death and bodyweight change,of which the viral load in lung were determined on day 3 after challenge.Results The GMTs of serum IgG antibody 7,14 and 21 d after the first dose were 152,230 and 264,while those of IgA in alveolar lavage fluid were 23,211 and 92,respectively.However,the GMTs of serum IgG antibody 7,14 and 21 d after the second dose were 348,919 and 1056,while those of IgA antibody in alveolar lavage fluid were 53,368 and 160,respectively.The protective rate of mice challenged 14 d after immunization with a single dose was 83.33%(5/6),while the weight loss decreased,and the lung viral load decreased significantly.However,the protective rate of mice immunized with two doses and challenged 14 d after the second dose was 100%(6/6),while few bodyweight loss was observed,and no virus was detected in lung.Conclusion Cold-adapted influenza virus vaccine strain AA-PR8 showed good immunogenicity in mice,which significantly decreased the viral load in lung and increased the survival rate of mice challenged with PR8 influenza virus.

关 键 词：流感疫苗 冷适应流感病毒 IGG抗体 IGA抗体 

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]