生产用流感病毒H3N2型疫苗株血凝素蛋白HA1的基因分析

Genetic Analysis of HA1 Gene of Influenza H3N2 Virus Strain for Vaccine Production

目的分析生产用流感病毒H3N2型疫苗株血凝素蛋白HA1基因变异对病毒特性的影响。方法比较2005～2008年间上海生物制品研究所流感病毒H3N2型各疫苗株的生产数据,并对H3N2型各疫苗株的HA1基因序列数据进行分析。结果各疫苗株中,A/NewYork/55/2004(NYMCX-157)的血凝素得率最高,A/Brisbane/10/2007(IVR-147)最低;2006～2007年度疫苗候选株A/Wisconsin/67/2005(NYMCX-161B)的病毒复制能力优于A/Hiroshima/52/2005(IVR-142);各疫苗株的氨基酸差异均未直接涉及到HA1蛋白二硫键组成位点,直接涉及到HA1蛋白抗原决定簇位点、HA1蛋白糖基化位点和HA蛋白受体结合位点的变异分别有3处(140、156和193位)、1处(165位)和1处(225位)。结论2005～2008年间各流感病毒疫苗株血凝素得率因株而异,HA1蛋白抗原决定簇位点变异属于正常的不同毒株间的差异;糖基化位点、二硫键组成位点和受体结合位点基本保守;还需进一步研究部分位点氨基酸变异是否与病毒复制能力密切相关,并探讨改善复制能力的可能性。

Objective To analyze the effect of HA1 gene variation on property of influenza H3N2 virus strain for vaccine production. Methods The data on production of influenza vaccine with various H3N2 virus strains by Shanghai Institute of Biological Products during 2005 ～ 2008 were compared, and those on HA1 gene sequences of the strains were analyzed. Results The HA yield of strain A / New York / 55 / 2004（NYMCX-157）was the highest, while that of strain A / Brisbane / 10 / 2007 / （IVR-147）was the lowest. The viral replication ability of strain A / Wisconsin / 67 / 2005 （NYMCX-161B）, a candidate vaccine strain during 2006～ 2007, was higher than that of strain A / Hiroshima / 52 / 2005 （IVR-142）. The amino acid variations of various strains showed no direct relationship to the sites in which disulfide bonds of HA1 protein were formed. However, three variations were directly related to antigenic determinants（sites 140, 156 and 193）, one to glycosylation site（site 165） and one to receptor-binding site（site 225） of HA1 protein. Conclusion The HA yields of various influenza vaccine virus strains during 2005～2008 were different. The variations at antigenic determinants of HA1 protein were normal difference between strains. The glycosylation, disulfide bond formation and receptor-binding sites were basically conserved. However, whether the amino acid variations at a part of sites are closely related to viral replication ability, as well as the possibility of improving the ability, are to be further studied.