流感病毒RNA聚合酶蛋白PB1在小鼠中可诱导亚型间交叉免疫保护

Cross protective immunity against influenza A virus between subtypes induced by influenza polymerase protein PB1 in mice

目的探索流感病毒RNA聚合酶PB2和PB1亚基作为实验性流感疫苗候选抗原的可能性。方法以复制型质粒(pSCA)为载体分别构建表达甲1型和甲3型流感PB2和PB1的复制型 DNA疫苗,免疫小鼠后分别用甲1型流感病毒(A/PR／8／34)进行鼻腔攻击,观察针对不同亚型流感病毒的复制型DNA疫苗的免疫保护效果。结果本实验所构建的复制型DNA疫苗在真核细胞中均可表达外源基因;本实验采用的复制型质粒载体(pSCA)与传统质粒载体(pcDNA3)在诱导小鼠产生抗体方面无差异,并且都诱导了偏向T_H1类的免疫反应;表达甲1型和甲3型流感PB1基因的复制型DNA 疫苗均可保护小鼠抵御甲1型流感病毒(A/PR／8／34)的攻击。结论表达甲型流感病毒PB1的复制型 DNA疫苗能保护小鼠抵御同型和异型流感病毒的攻击,本实验为流感疫苗研究提供新的候选抗原。

Objective To investigate the possibility of the influenza RNA polymerase proteins PR2 and PB1 served as the alternative antigens of the experimental influenza vaccine. Methods The replicative DNA vaccines encoding the PB2 or PB1 protein from different influenza viruses（A1/PR/8/34 and A3/jingke/95/30） were constucted respectively;the vaccine inoculated mice were attacked by influenza A virus（A/PB/8/34） through nasal pathway to see the protective efficiency of the replicative DNA vaccine. Results The replicative DNA vaccines encoding PB2 and PB1 protein from different subtypes of influenza A were able to express the interest proteins in eukaryotic cells; there was no difference between the antibodies induced by the replicative plasmid（pSCA）and the conventional plasmid（pcDNA3）, and TH 1-bias responses were both induced by these DNA plasmids; the mice immunized by the PB1 DNA vaccine could survive by the challenges of the homologous and heterogenous influenza virus. Conclusion The mice immunized by the replicative DNA vaccine encoding PB1 protein of influenza A can survive by the challenge of the homologous and heterologous influenza virus. A new alternative antigen of the experimental influenza vaccine is promising and worth to be further studied.