中国百日咳疫苗生产用菌株完成图基因组遗传分析

Genetic analysis of pertussis strain used for vaccine production in China in complete map genome level

目的对我国百日咳疫苗生产用菌株进行完成图基因组的遗传分析。方法利用PacBio Sequel三代测序平台与Illumina二代测序平台相结合的方式,对百日咳疫苗生产用原始菌株进行完成图基因组测序,并进行基因组组分分析、基因功能注释以及比较基因组分析。同时对企业生产过程中不同代次菌株进行遗传稳定性分析。结果获得了百日咳疫苗原始菌株及其生产过程不同代次菌株的完成图基因组,基因组长度4.1 Mb,GC含量68%,不同代次间基因组结构稳定;获得并分析了pt、pha、prn、fim2、fim3、act、tct、ompA、BrKA、rplD、BP1569等具有免疫原性或潜在免疫原性的基因,不同代次间基因未发生变异。结论本研究获得了结构完整、背景清晰的百日咳疫苗生产用菌株完成图基因组,为我国百日咳疫苗生产用菌种的质量控制提供了依据,同时也为百日咳分子流行病学的研究提供了参考。

Objective To carry out genetic analysis of complete map genome of strains used for pertussis vaccine production in China.Methods The complete map genome of pertussis vaccine original seed for production use was sequenced by combining PacBio Sequel third-generation sequencing platform and Ilumina second-generation sequencing platform,and the genome components analysis,gene function annotation and comparative genome analysis were performed.Simultaneously,the genetic stability of different generations of strains in the production process of enterprises was analyzed.Results The complete map genome of the original strain of pertussis vaccine and its different generations in the production process was obtained,with the genome length of 4.1 Mb,the GC content of 68%,and the stable genome structure among different generations.Immunogenic or potentially immunogenic genes such as pt,pha,prn,fim2,fim3,act,tct,ompA,BrKA,rplD and BP1569 were obtained and analyzed,and no occured in different generations of genes.Conclusion In this study,the complete map genome of pertussis strains for vaccine production with complete structure and clear background was obtained,which provided a basis for the quality control of pertussis strains for vaccine production in China,and also provided a reference for the study of molecular epidemiology of pertussis.