甲型H3N2亚型流感病毒重配疫苗株产量评估与基因特性研究  

Study on Gene Characteristics and Yield of Reassortant Influenza A(H3N2)Vaccine Viruses

作　　者：白红岩 李希妍[1] 黄维娟[1] 隗合江[1] 成艳辉[1] 唐静[1] 王大燕[1] 辛丽[1] BAI Hongyan;LI Xiyan;HUANG Weijuan;WEI Hejang;CHENG Yanhui;TANG Jing;WANG Dayan;XIN Li(National Institute for Viral Disease Control and Prevention,China CDC,NHC Key Laboratory of Medical Virology and Viral Diseases,Beijing102206,China)

机构地区：[1]中国疾病预防控制中心病毒病预防控制所,国家卫生健康委医学病毒和病毒病重点实验室,北京102206

出　　处：《病毒学报》2024年第6期1246-1254,共9页Chinese Journal of Virology

基　　金：北京市自然科学基金-海淀原始创新联合基金(项目号:L212006),题目:流感病毒高产疫苗株基因特性研究与疫苗产量评价。

摘　　要：本研究基于我国流感监测数据,筛选2023年我国甲型H3N2亚型流感病毒代表株,利用经典重配方法构建鸡胚高产重配疫苗株(High growth reassortants,HGR),研究基因组成特性对疫苗产量的影响。结果显示利用筛选出的5株代表株(HA属于2a.3a.1分支)构建18株HGR,其HA滴度是野毒株(Wild type,WT)的1-32倍,HA蛋白产量是WT的1~15倍。18株重配株内部基因插入母本毒株内部基因的数量为1~6个片段。HGR表面基因和内部基因均影响病毒生长和复制,WT自身产量较高有利于获得较高HA产量的重配株。HGR的六个内部基因中,鸡胚高产母本毒株A/PR8/32(PR8)的M基因是甲型H3N2亚型流感病毒HGR的高频重配基因,对提高产量贡献最大。PR8的PB1基因与H3N2流感病毒表面HA和NA基因兼容性最差。HGR中来自母本毒株的内部基因数目与疫苗产量不成线性关系,存在随机性。本研究对于探究流感HGR产量与表面基因和内部基因的关系,筛选重配用WT和HGR具有重要意义。Based on the influenza surveillance data in China,five representative strains of influenza A(H3N2)2a.3a.1 clade viruses circulating in 2023 were selected,and 18 high-growth reassortant(HGR)vaccine strains were constructed using classical reassortment methods in embryonated chicken eggs.The study aimed to evaluate the impact of gene composition on vaccine yield.The results showed that the hemagglutinin(HA)titer of the HGR strains increased by 1 to 32 times,and the HA protein yield increased by 1 to 15 times compared to wild-type(WT)strains.The number of internal genes derived from the parental donor strain inserted into the reassortants ranged from 1 to 6 segments.Both surface and internal genes were found to affect the growth and replication of the virus.Higher yields of wild-type strains were associated with reassortants producing higher HA protein levels.Among the six internal genes of the HGRs,the M gene from the donor strain A/PR8/32(PR8)was the most frequently reassorted gene and contributed the most to increase the yield.However,the PB1 gene of PR8 was the least compatible with the HA and neuraminidase(NA)surface genes of H3N2 influenza viruses.The number of internal genes reassorted from PR8 into the HGRs was not linearly related to vaccine yield,indicating randomness in the reassortment process.This study provides important insights into the relationship between yield and gene characteristics of reassortant influenza vaccine strains and contributes to the selection of wild-type strains with high potential for vaccine production.

关 键 词：流感病毒 H3N2亚型 产量 重配疫苗株 基因特性 

分 类 号：R373.1[医药卫生—病原生物学]