重组禽流感病毒H5亚型灭活疫苗的质量分析及发展方向  

Quality Analysis and Development Direction of Recombinant Avian Influenza Inactivated Vaccine(H5 subtype)

作　　者：杨劲松[1] 吴涛[1] 李金祥[2] YANG JinSong1, WU Tao1, LI JinXiang2(1.China Institute of Veterinary Drugs Control, Beijing 100081; 2.Chinese Academy of Agricultural Sciences, Beijing 10008)

机构地区：[1]中国兽医药品监察所,北京100081 [2]中国农业科学院,北京100081

出　　处：《中国农业科学》2018年第17期3397-3404,共8页Scientia Agricultura Sinica

基　　金：国家重点研发计划项目(2017YFF0208600)

摘　　要：对主要用于我国高致病性禽流感防控的重组禽流感病毒H5亚型灭活疫苗的种类和使用情况,以及国内高致病禽流感流行株的主要分支情况作一介绍。随着病毒抗原性的不断变异,疫苗毒株也需随之进行更换,因此必须使用匹配相应分支的疫苗才能取得理想的防控效果。目前国内重组禽流感病毒H5亚型灭活疫苗的生产现状是共有10家生产企业,其中2个厂家采用悬浮细胞工艺生产,其余8个厂家均采用鸡胚工艺进行疫苗生产。笔者根据企业上报的产品批签发报告情况,以2016年至2017年农业部规定的高致病性禽流感强制免疫疫苗重组禽流感病毒H5亚型三价灭活疫苗(Re-6株+Re-7株+Re-8株)为例,着重从疫苗的安全性和效力两方面对4家重组禽流感灭活疫苗生产企业共计488批次产品的批签发检验数据进行了质量分析。从Re-6株、Re-7株、Re-8株不同组分效价的比较可以看出,所有批次疫苗抗体效价几何平均滴度(GMT)至少高于国家标准1个滴度以上,而Re-6株和Re-8株组分抗体效价(GMT)高于国家标准2个滴度以上。虽然产品的效价都超过了国家标准,但抗体水平还是参差不齐,较高产品的3个组分抗体效价(GMT)比较低的要高出1.5个滴度以上。各生产企业产品批间差异较大,这虽有生产工艺不断成熟和优化的因素,但对于相近批次产品批间差异出现较大差异,则说明企业生产工艺并不十分稳定。4个企业在2017年生产的疫苗各组分抗体效价GMT整体水平均比2016年有所提高,说明生产工艺的不断成熟和优化,企业对产品质量的进一步严格把关。我国禽流感病毒灭活疫苗含有的甲醛和细菌内毒素是造成疫苗副反应的直接原因,因此通过生产工艺改进,降低疫苗中甲醛和细菌内毒素的含量,可以降低疫苗的副反应。核酸疫苗是当前禽流感疫苗研究发展的前沿技术,是现阶段禽流感疫苗硏制中最具理想前�This paper introduces the types and use of the recombinant Avian Influenza virus H5 subtype inactivated vaccine, which is mainly used for highly pathogenic Avian Influenza prevention and control, as well as the main branches of the highly pathogenic Avian Influenza epidemic strains in China. As the antigenicity of virus continues to mutate, the vaccine strain needs to be replaced, therefore, the vaccine that matches the corresponding branch must be used to achieve the desired control effect. At present, the current domestic production of recombinant Avian Influenza virus H5 subtype inactivated vaccine is that there are 10 manufacturers, 2 of them are produced by suspension cell technology, and the remaining 8 manufacturers all adopt chicken embryo technology for vaccine production. According to the situation of these products reported by the manufacturers, the compulsory immunized recombinant avian influenza virus H5 subtype trivalent inactivated vaccine（Re-6 strain ＋Re-7 strain ＋Re-8 strain）, which was against the highly pathogenic avian influenza stipulated by the Ministry of agriculture from 2016 to 2017, was taken as an example in this paper. Subsequently, focusing on the safety and efficacy of the vaccine, the qualities of the 488 batches inspection data from four recombinant Avian Influenza inactivated vaccine manufacturers were analyzed. The antibody titer comparison of Re-6, Re-7 and Re-8 strain show that the geometric mean titer（GMT） of all batch vaccines is at least 1 titer above the national standard, while the antibody titer of Re-6 and Re-8 strain（GMT） are at least 2 titers above the national standard. Even though the titer of the product exceeds the national standard, the antibody level is still uneven, and the manufacturer with higher GMT of 3 components shall have 1.5 titers higher than the manufacturer with lower ones. The difference between batches of the manufacturer is still relatively significant. Although there are factors for the continuous maturation and optimization of the

关 键 词：重组禽流感病毒H5亚型灭活疫苗 生产现状 质量分析 工艺改进 

分 类 号：S852.65[农业科学—基础兽医学]