冷适应减毒B型流感病毒疫苗候选株的制备及鉴定(英文)  

Development and Identification of a Live Attenuated Influenza B Virus Vaccine Candidate

作　　者：杨鹏辉[1] 安文琪[1,2] 石辛甫[1] 段跃强[1] 罗德炎[1] 张鹏飞[1] 唐冲[1] 邢丽[1] 张玉静[2] 刘秀梵[3] 王希良[1] 

机构地区：[1]军事医学科学院微生物流行病研究所病原微生物生物安全国家重点实验室,北京100071 [2]吉林大学畜牧兽医学院,长春130000 [3]扬州大学农业部畜禽传染病学重点开放实验室,扬州225009

出　　处：《生物化学与生物物理进展》2009年第3期358-363,共6页Progress In Biochemistry and Biophysics

基　　金：supported by a grant from Chinese National Programsfor High Technology Research and Development (2006AA02Z450)~~

摘　　要：以冷适应、温度敏感、减毒的B/Ann Arbor/1/66流感病毒株作为重配病毒骨架,对其6个内部基因片段进行了全基因合成,同时人工引入9个氨基酸突变.构建了8个基因的拯救载体,经测序获得序列准确的拯救质粒,命名为:pAB121-PB1,pAB122-PB2,pAB123-PA,pAB124-HA,pAB125-NP,pAB126-NA,pAB127-M和pAB128-NS.在成功拯救冷适应A型流感病毒的基础上,利用反向遗传学技术成功获救了具有感染性的重配B型流感病毒株,命名为rMDV-B.该重配病毒株以B/Ann Arbor/1/66为病毒骨架,其中HA和NA来源于2006～2007年当年流行株B/Malaysia/2506/2004.rMDV-B在鸡胚尿囊液和MDCK细胞中的HA效价可达1∶64～1∶512.实验结果暗示:从单一供体病毒株可以产生有效的减毒活B型流感病毒疫苗候选株,能够为将来人用流感疫苗的设计提供可借鉴的模型.A cold-adapted （ca）, temperature sensitive （ts）, live attenuated influenza B virus strain B/Ann Arbor/1/66 was chosen for influenza virus rescue research, in which six internal gene segments, PB1, PB2, PA, NP, M, NS, were fully synthesized and nine amino acid substitutions were artificially alter by human intervention. The resultant B/Ann Arbor/1/66 plasmids were named as pAB 121-PB 1, pAB122-PB2, pAB123-PA, pAB124-HA, pAB125-NP, pAB126-NA, pAB127-M and pAB128-NS, respectively. A recombinant influenza A virus was previously generated entirely from cloned cDNA. An infectious recombinant influenza B virus was generated here, and designated as rMDV-B, by plasmid-based reverse genetics. The rMDV-B virus contained HA and NA genes from an epidemic influenza B virus strain B/Malaysia/2506/2004 in the background of internal genes derived from influenza B virus strain B/Ann Arbor/1/66. HA titer ofrMDV-B in MDCK cells and embryonated chicken eggs ranged from 1 ：64 to 1 ： 512. The results may allow an effective live influenza B vaccine to be produced from a single master strain, providing a model for the design of future live human influenza vaccines.

关 键 词：B型流感病毒 反向遗传学 8质粒拯救系统 重组流感病毒 

分 类 号：R183.3[医药卫生—流行病学] R392.1[医药卫生—公共卫生与预防医学]