柯萨奇病毒A组16型手足口病疫苗研究现况

王乾芬; 原国强; 吴羽晨; 徐萍; 徐小博

doi:10.19837/j.cnki.ahyf.2022.06.012

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安徽预防医学杂志 ›› 2022, Vol. 28 ›› Issue (6) : 487-489. DOI: 10.19837/j.cnki.ahyf.2022.06.012

综述

柯萨奇病毒A组16型手足口病疫苗研究现况

王乾芬¹, 原国强², 吴羽晨¹, 徐萍¹, 徐小博¹

作者信息 +

Research progress of Coxsackievirus group A 16 vaccine

WANG Qian-fen^*, YUAN Guo-qiang, WU Yu-chen, XU Ping, XU Xiao-bo

Author information +

文章历史 +

摘要

手足口病(hand,foot and mouth disease,HFMD)严重影响着婴幼儿健康。肠道病毒A组71型(enterovirus A71,EV71)及柯萨奇病毒A组16型(coxsackievirus A16,CA16)是引起手足口病的主要病原体,曾在全球多个国家或地区暴发,接种疫苗是预防手足口病的有效途径,EV71疫苗已上市,但是CA16疫苗相关研发进展较缓慢,目前仍无相关疫苗上市。本文对CA16型灭活疫苗、减毒活疫苗、病毒样颗粒(virus-like particle,VLP)疫苗、DNA疫苗、重组嵌合病毒疫苗及亚单位疫苗的相关研究进展做一综述。

Abstract

Hand,foot and mouth disease (HFMD) is an infectious disease that seriously affects the health of infants and young children.Enterovirus A71 (EV71) and Coxsackievirus A16 (CA16) are the main pathogens causing HFMD.HFMD has been outbreaks in many countries or regions around the world.Vaccination is an effective way to prevent HFMD.EV71 vaccine has been marketed,but CA16 vaccine research and development progress is relatively slow.So far,there is still no CA16-related vaccine on the market.This article reviews the research progress of CA16 inactivated vaccine,live attenuated vaccine,virus-like particle (VLP) vaccine,DNA vaccine,recombinant chimeric virus vaccine and subunit vaccine.

导出引用

王乾芬, 原国强, 吴羽晨, 徐萍, 徐小博. 柯萨奇病毒A组16型手足口病疫苗研究现况[J]. 安徽预防医学杂志. 2022, 28(6): 487-489 https://doi.org/10.19837/j.cnki.ahyf.2022.06.012

WANG Qian-fen, YUAN Guo-qiang, WU Yu-chen, XU Ping, XU Xiao-bo. Research progress of Coxsackievirus group A 16 vaccine[J]. Anhui Journal of Preventive Medicine. 2022, 28(6): 487-489 https://doi.org/10.19837/j.cnki.ahyf.2022.06.012

中图分类号： R512.5

参考文献

[1] 冯骁,李琦涵.柯萨奇病毒A16型疫苗的研究进展[J].中国生物制品学杂志,2021,34(3):357-361.
[2] 靳卫平,钱莎莎,申硕.手足口病相关肠道病毒及疫苗的研究进展[J].中国生物制品学杂志,2021,34(11):1273-1283.
[3] 国家食品药品监督管理总局.食品药品监督管理总局批准肠道病毒71型灭活疫苗生产上市[EB/OL].(2015—12-03)[2022-04-15].https://www.nmpa.gov.cn/yaopin/ypjgdt/20151203164201285.html.
[4] Mao Q,Wang Y,Yao X,et al.Coxsackievirus A16:epidemiology,diagnosis and vaccine[J].Hum Vaccin Immunother,2014,10(2) :360-367.
[5] 李小平,吴亦栋,周俊,等.柯萨奇病毒 A 组 16 型病毒株 VP1基因序列测定及进化分析研究[J].中国全科医学,2018,21( 5) :546-550.
[6] Li JP,Liao Y,Zhang Y,et al.Experimental infection of tree shrews (Tupaia belangeri) with Coxsackie virus A16[J].Zoological Res,2014,35(6):485-491.
[7] 王晶晶.CA16 感染恒河猴模型以及相关病原和免疫学特性研究[D].北京:中国医学科学院北京协和医学院,2017.
[8] 徐英莉,郭姗姗,耿子涵,等.CA16型手足口病BALB/c乳鼠模型的建立 [J].中国实验动物学报,2021,29(3):316-322.
[9] Mao Q,Wang Y,Gao R,et al.A neonatal mouse model of Coxsackievirus A16 for vaccine evaluation [J].J Virol,2012,86(22):11967.
[10] Sun YS,Li YJ,Xia Y,et al.Coxsackievirus A16 induced neurological disorders in young gerbils which could serve as a new animal model for vaccine evaluation [J].Sci Rep,2016,6:34299.
[11] 李华,岳磊,张也,等.不同灭活剂对柯萨奇病毒 A 组 16 型免疫原性的影响[J].中国生物制品学杂志,2020,33(11):1217-1229.
[12] Lim H,In H J,Lee J A,et al.The immunogenicity and protection effect of an inactivated coxsackievirus A6,A10,and A16 vaccine against hand,foot,and mouth disease[J].Vaccine,2018,36(24):3445-3452.
[13] 张浩然,姜莉,杨二霞,等.不同佐剂对柯萨奇病毒A组16型灭活疫苗诱导小鼠体液免疫应答的影响[J].药物评价研究,2020,43(5):829-834.
[14] Sun YS,Li YJ,Xia Y,et al.Coxsackievirus A16 induced neurological disorders in young gerbils which could serve as a new animal model for vaccine evaluation[J].Sci.Rep,2020,6:34299.
[15] Caine EA,Fuchs J,Das SC,et al.Efficacy of atrivalent hand,foot,and mouth disease vaccine against enterovirus 71 and Coxsackieviruses A16 and A6 in mice[J].Viruses,2015,7(11):5919-5932.
[16] Zhang G,Hu B,Huo Y,et al.Amino acid substitutions in VP2,VP1,and 2C attenuate a coxsackievirus A16 in mice[J].Microb Pathog,2021,150:104603.
[17] 姜广菊.柯萨奇病毒 A 组 16 型减毒疫苗候选株的筛选[D].北京:中国医学科学院北京协和医学院,2014.
[18] 张也.柯萨奇病毒A组16型实验性减毒活疫苗关键工艺研究[D].北京:中国医学科学院北京协和医学院,2018.
[19] Yang T,Xie T,Song X,et al.Safety and immunogenicity of an experimental live combination vaccine against enterovirus 71 and coxsackievirus A16 in rhesus monkeys[J].Hum Vaccin Immunother,2020,16(7):1586-1594.
[20] 陈祥鹏,毛乃颖,张勇,等.柯萨奇病毒 A 组 16 型病毒样颗粒的制备及其免疫原性[J].中国生物制品学杂志,2014,27(11):1361-1368+1374.
[21] Somasundaram B,Chang C,Fan YY,et al.Characterizing Enterovirus 71 and Coxsackievirus A16 Virus-like Particles Production in Insect Cells,Methods,2016,95:38-45.
[22] Zhao H,Li HY,Han JF,et al.Virus-like particles produced in Saccharomyces cerevisiae elicit protective immunity against Coxsackievirus A16 in mice[J].Appl Microbiol Biotechnol,2013,97(24):10445-10452.
[23] Feng Q,He Y,Lu J.Virus-like particles produced in Pichia pastoris induce protective immune responses against Coxsackievirus A16 in mice[J]. Med Sci Monit,2016,23(22):3370-3382.
[24] Zhang C,Liu Q,Ku Z,et al.Coxsackievirus A16-like particles produced in Pichia pastoris elicit high-titer neutralizing antibodies and confer protection against lethal viral challenge in mice[J].Antiviral Research,2016,129:47-51.
[25] Tung WS,Bakar SA,Sekawi Z,et al.DNA vaccine constructs against enterovirus 71 elicit immune response in mice[J].Genet Vaccines Ther,2007,5:6.
[26] 刘泽,白冰珂,高蓉,等.利用减毒沙门菌递送的柯萨奇病毒 A16 型 VP1 基因重组质粒的构建和鉴定[J] .细胞与分子免疫学杂志,2011,27(5):501-503.
[27] Yang L,Liu Y,Li S,et al.A novel inactivated Enterovirus 71 vaccine can elicit cross-protective immunity against coxsackievirus A16 in mice[J].Vaccine,2016,34(48):5938-5945.
[28] Lyu K,He YL,Li HY,et al.Crystal structures of yeast-produced Enterovirus 71 and Enterovirus 71 /coxsackievirus A16 chimeric virus-like particles provide the structural basis for novel vaccine design against hand-foot-and-mouth disease[J].J Virol,2015,89(12):6196-6208.
[29] Zhao H,Li HY,Han JF,et al.Novel recombinant chimeric virus-like particle is immunogenic and protective against both enterovirus 71 and coxsackievirus A16 in mice[J].Sci Rep,2015,5:7878.
[30] 李晓楠,罗德炎,赵忠鹏,等.手足口病CA16型 VP1 亚单位疫苗的构建制备及免疫原性初步分析[J].中华微生物学和免疫学杂志,2010,30(3):250-255.
[31] 李广红,郝瑜,刘顺涛,等.柯萨奇病毒 A16 粘膜疫苗的制备及其免疫效果研究[J].中国热带医学,2017,17(9) :857-861.
[32] 中国疾病预防控制中心.肠道病毒 71 型灭活疫苗使用技术指南[EB /OL] .(2016-06-08)[2022-04-15].http://www.chinacdc.cn/zxdt/201606/t20160608_131032.html.