疫苗接种人群和安慰剂人群肠道病毒A71型基因特征分析

Genetic Characteristics of Enterovirus A71 Isolated from Subjects Receiving Enterovirus A71 Inactivated Vaccine or Placebo

目的 分析比较健康人群接种肠道病毒A71型（Enterovirus A71,EV-A71）灭活疫苗和安慰剂后EV-A71感染的基因特征。方法 按照1∶1配对的病例对照研究,统计比较接种组和安慰剂组人群中EV-A71导致相关疾病流行病学差异;利用Sequencher 5.0和MEG5.0等生物信息学软件分析不同组别的EV-A71的VP1区核苷酸和氨基酸差异,获得不同人群中EV-A71的分子流行病学特征。结果 本研究共有接种组病例13例（0.3%）,安慰剂组106例（2.1%）;EV-A71相关疾病发生呈现夏季和冬季两个高峰,主高峰集中在夏季（4~7月）,次高峰集中在冬季（11~12月）,以安慰剂组人群为主。所有EV-A71毒株与中国2007年以来其他省代表毒株相同,属于C4a亚型;各序列同源性较高,其核苷酸同源性为95.16%~100%,氨基酸同源性为96.94%~100%,与周边省市近3年序列亲缘关系较相近。结论 本研究安慰剂组人群中EV-A71除夏季流行外,在冬季仍有少量EV-A71的循环传播;EV-A71仍为C4a亚型且同源性较高,与周边省市的C4a亚型序列存在共同进化关系。

Objective To compare genetic characteristics of enterovirus A71（EV-A71） isolated from subjects receiving EV-A71 inactivated vaccine or placebo.Methods Using a 1-to-1 matched case-control design,the epidemiologic characteristics of diseases caused by EV-A71 were determined in both vaccine and placebo groups.All VP1 nucleotide sequences were analyzed with Sequencher 5.0 and MEG5.0 Software to compare molecular epidemiological characteristics between the two groups.Results 13 EV-A71 associated cases（0.3%） were reported in the vaccine group,and 106 cases（2.1%） were reported in the placebo group.The incidences of EV-A71 cases showed two epidemic peaks： a main one in summer（from April to July）,and another in winter（from November to December）, seen mainly in the control group.All EV-A71 strains in this study showed a high nucleotide homology with strains isolated since 2007 in other provinces in China;all were sub-genotype C4 a.A high degree of homology of nucleotides（95.16%-100%） and amino acids（96.94%-100%） was found among EVA71 strains in this study,and the closest phylogenetic relations were with sequences from nearby provinces.Conclusions EV-A71 circulated inthe placebo group during winter,following the summer epidemic.All EV-A71 strains in this study were sub-genotype C4 a and showed a high nucleotide homology with each other.The phylogenic tree showed that all strains in this study had coevolved with strains isolated in nearby provinces.