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广东省是我国手足口病的高发区域。肠道病毒71型(Enterovirus 71, EV-A71)是导致重症手足口病的主要致病病原。2008年我国将手足口病纳入丙类法定传染病以来,C4a是EV-A71的主要流行基因亚型,也是当前已上市的EV-A71灭活疫苗对应的疫苗株。本研究首次报道了广东省在2024年2月存在一例EV-A71 B5基因亚型感染散发病例,并对分离毒株进行了全基因组测序、分子流行病学以及抗原特异性研究。通过病毒分离、全基因组测序及分子进化分析,发现该分离株(R305)与近年国内其他区域监测的EV-A71 B5相似性较低(VP1区基因相似性92.81%~96.40%)而与越南分离株具有更高度的核苷酸序列一致性(VP1区基因相似性99.10%),提示其外源输入的可能性。为验证C4a基因型灭活疫苗对B5基因型的保护作用,本研究对20例EV-A71疫苗接种后的代表性血清开展交叉血清中和试验。研究结果表明,接种EV-A71 C4a疫苗个体的血清对B5基因亚型具有交叉中和反应,几何平均滴度为97.01,略低于C4a基因亚型的119.4,但差异无统计学意义(P>0.05)。当前,我国EV-A71处于较低流行水平,EV-A71 B5作为亚太地区主要流行株在我国多个地区陆续监测发现,可能对国内EV-A71流行趋势产生影响。手足口病监测网络需进一步对国内流行的B5基因型序列变异趋势、致病性以及抗原性开展持续监测,以应对新病毒基因型潜在暴发流行的风险。
Abstract:Guangdong Province is one of the regions in China with a high incidence of hand, foot and mouth disease(HFMD). Enterovirus A71(EV-A71) is the primary pathogen responsible for severe HFMD. Since HFMD was classified as a Category C notifiable infectious disease in China in 2008, the C4a subgenotype has been the predominant circulating strain of EV-A71 and serves as the vaccine strain for currently licensed inactivated vaccines. Here, we report for the first time a sporadic case of EV-A71 subgenotype B5 infection in Guangdong Province in February 2024.The isolated strain(R305) was characterized by viral isolation, wholegenome sequencing, and molecular epidemiological and antigenic analyses. Phylogenetic analysis revealed that R305 showed relatively low nucleotide similarity with other B5 strains detected in China in recent years(92.81%–96.40% similarity in the VP1 region), but exhibited high similarity with Vietnamese isolates(99.10% in the VP1 region), suggesting possible importation. To assess whether the C4a-based inactivated vaccine provides cross-protectio against the B5 subgenotype, cross-neutralization assays were performed with 20 representative post-vaccination serum samples. The results demonstrated that sera from vaccine recipients exhibited crossneutralizing activity against the B5 subgenotype(geometric mean titer [GMT] = 97.01), which was slightly lower than that against the homologous C4a subgenotype(GMT = 119.4), though the difference was not statistically significant(P>0.05). Currently, EV-A71 circulation in China remains at a relatively low level. However, EV-A71 B5, which is the predominant subgenotype in the Asia-Pacific region, has been increasingly detected across multiple provinces in China and may influence future epidemiological trends. Continuous surveillance g of sequence variation, pathogenicity, and antigenicity of the B5 subgenotype is warranted to mitigate the potential risk of outbreaks caused by emerging EV-A71 genotypes.
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基本信息:
DOI:10.13242/j.cnki.bingduxuebao.250218
中图分类号:R373.2
引用信息:
[1]颜羽西,谢春燕,曹嘉钿,等.广东省EV-A71 B5基因型的分离鉴定、分子流行病学及抗原性研究[J].病毒学报,2025,41(06):1723-1730.DOI:10.13242/j.cnki.bingduxuebao.250218.
基金信息:
广东省基础与应用基础研究基金项目(项目号:2023A1515011927),题目:新型冠状病毒SARS-CoV-2 furin酶切位点缺失机制研究; 广东省新发传染病应急检测技术研究与应用重点实验室开放课题(项目号:2023B1212010010),题目:呼吸道多病原核酸质控品的研制; 广东省疾病预防控制中心立项支持人才项目(项目号:0720240122),题目:建立自主可控的智慧化本地病原数据库和精准、快速的病原鉴定、分子溯源及特征分析平台~~