柯萨奇病毒A组16型分子流行病学和疫苗研究进展Research Advances in Molecular Epidemiology and Vaccines of Coxsackievirus A16
陈祥鹏;檀晓娟;许文波;
摘要(Abstract):
柯萨奇病毒A组16型(Coxsackievirus A16,CVA16)是引起手足口病(Hand,foot,and mouth disease,HFMD)的重要致病原,常与另一重要病原体肠道病毒71型(Enterovirus 71,EV-A71)共同或交替流行。该病毒在世界多个国家和地区引起过暴发流行,成为重要的公共卫生问题。CVA16可分为A和B两个基因型;其中基因型B可以分成B1和B2两个基因亚型;B1亚型又可进一步分成B1a、B1b和B1c三个进化分支。基因型A与B2在世界范围内已不再流行;我国大陆分离到的CVA16毒株均属B1a和B1b进化分支。CVA16感染多为自限性轻症,但亦可引起严重的并发症,甚至引起患者死亡。目前尚无针对该病毒的有效药物或治疗手段,研发安全有效的疫苗成为控制该病毒的重要措施。随着EV-A71疫苗三期临床试验的成功完成,CVA16疫苗的研究也显得更加迫切。多家机构正在研究各种类型的CVA16疫苗,包括灭活疫苗、基因工程疫苗及DNA疫苗等。本文就CVA16的分子流行病学及其疫苗研究进展进行了综述。
关键词(KeyWords): 手足口病;柯萨奇病毒A组16型;基因型;疫苗
基金项目(Foundation): (艾滋病和病毒性肝炎等重大传染病防治科技重大专项)病毒性传染病病原谱流行规律及变异研究(2013ZX10004202),(2012ZX10004201-003)
作者(Authors): 陈祥鹏;檀晓娟;许文波;
DOI: 10.13242/j.cnki.bingduxuebao.002536
参考文献(References):
- [1]Yang F,Zhang T,Hu Y,et al.Survey of enterovirus infections from hand,foot and mouth disease outbreak in China,2009[J].Virol J,2011;8:508.
- [2]Chang L Y,Lin T Y,Huang Y C,et al.Comparison of enterovirus 71and coxsackie-virus A16clinical illnesses during the Taiwan enterovirus epidemic,1998[J].Pediatr Infect Dis J,1999,18:1092-1906.
- [3]Ang L W,Koh B K,Chan K P,et al.Epidemiology and control of hand,foot and mouth disease in Singapore,2001-2007[J].Ann Acad Med Singapore,2009,38:106-112.
- [4]Wright H T Jr,Landing B H,Lennette E H,et al.Fatal infection in an infant associated with Coxsackie virus group A,type 16[J].N Engl J Med,1963,268:1041-1044.
- [5]Ogilvie M M,Tearne C F.Spontaneous abortion after hand-foot-and-mouth disease caused by Coxsackie virus A16[J].Br Med J,1980,281:1527-1528.
- [6]Goto K,Sanefuji M,Kusuhara K,et al.Rhombencephalitis and coxsackievirus A16[J].Emerg Infect Dis,2009,15:1689-1691.
- [7]Wang C Y,Li L F,Wu M H,et al.Fatal coxsackievirus A16infection[J].Pediatr Infect Dis J,2004,23:275-276.
- [8]Legay F,Leveque N,Gacouin A,et al.Fatal coxsackievirusA-16pneumonitis in adult[J].Emerg Infect Dis,2007,13:1084-1086.
- [9]Zhang W,Wang Y G,Yang Z H,et al.Severe HandFoot-and-Mouth Disease Caused by Mixed Infection of Enterovirus 71and Coxsackie A16:Report of 6Cases[J].Chinese General Practice,2011,29:3341-3343.
- [10]Sickles G M,Mutterer M,Feorino P,et al.Recently classified types of Coxsackievirus,group A;behavior in tissue culture[J].Proc Soc Exp Biol Med,1955,90(2):529-531.
- [11]李兰娟.手足口病[M].北京:科学出版社,2009,1-2,59-61.
- [12]Iwai M,Masaki A,Hasegawa S,et al.Genetic changes of coxsackievirus A16and enterovirus 71isolated from hand,foot,and mouth disease patients in Toyama,Japan between 1981and 2007[J].Jpn J Infect Dis,2009,62:254-259.
- [13]Perera D,Yusof M A,Podin Y,et al.Molecular phylogeny of modern coxsackievirus A16[J].Arch Virol,2007,152:1201-1208.
- [14]Zhang Y,Wang D,Yan D,et al.Molecular evidence of persistent epidemic and evolution of subgenotype B1coxsackievirus A16-associated hand,foot,and mouth disease in China[J].J Clin Microbiol,2010,48:619-622.
- [15]Zong W,He Y,Yu S,et al.Molecular phylogeny of Coxsackievirus A16in Shenzhen,China,from 2005to2009[J].J Clin Microbiol,2011,49:1659-1661.
- [16]Chen X P,Tan X J,Li J,et al.Molecular epidemiology of Coxsackievirus A16:intratype and prevalent intertype recombination identified[J/OL].PLoS One,2013,8(12):e82861.
- [17]Hosoya M,Kawasaki Y,Sato M,et al.Genetic diversity of coxsackievirus A16associated with hand,foot,and mouth disease epidemics in Japan from 1983to2003[J].J Clin Microbiol,2007,45:112-120.
- [18]崔爱利,许文波,李秀珠,上海市2002年柯萨奇病毒A组16型基因特征分析[J].中国疫苗和免疫,2009,15(2):135-140.
- [19]Zhao K,Han X,Wang G,et al.Circulating coxsackievirus A16identified as recombinant type A human enterovirus,China[J].Emerg Infect Dis,2011,17:1537-1740.
- [20]杨文升.104例儿童重症手足口病的临床特征分析[J].重庆医学,2011,40(17):1722-1727.
- [21]Jia L,Zhao C S,Zhang L,et al.Comparisons of epidemiological and clinical characteristics in children with hand-foot-mouth disease caused by Enterovirus 71and Coxackievirus A16[J].Zhong guo Dang Dai Er Ke Za Zhi,2011Aug,13(8):635-637.
- [22]Qu M,Li J,Jia L,et al.Etiology of hand-foot-andmouth disease and genetic characteristics of Coxsackievirus A16in Beijing,2009[J].Bing Du Xue Bao,2010Nov,26(6):432-436.
- [23]Zhu F C,Meng F Y,Li J X,et al.Efficacy,safety,and immunology of an inactivated alum-adjuvant enterovirus 71vaccine in children in China:a multicentre,randomised,double-blind,placebo-controlled,phase 3trial[J].Lancet,2013,381(9882):2024-2032.
- [24]Cai Y,Liu Q,Huang X,et al.Active immunization with a Coxsackievirus A16 experimental inactivated vaccine induces neutralizing antibodies and protects mice against lethal infection[J].Vaccine,2013,31:2215-2221.
- [25]Chong P,Guo M S,Lin F H,et al.Immunological and biochemical characterization of coxsackie virus A16viral particles[J/OL].PLoS One,2012,7:e49973.
- [26]Wu T C,Wang Y F,Lee Y P,et al.Immunity to avirulent enterovirus 71and coxsackie A16virus protects against enterovirus 71infection in mice[J].J Virol,2007,81:10310-10315.
- [27]Mao Q,Wang Y,Gao R,et al.A neonatal mouse model of coxsackievirus A16for vaccine evaluation[J].J Virol,2012,86:11967-11976.
- [28]杨永娟,郝春生,李懿等.柯萨奇病毒A组16型VP1蛋白的原核表达及其免疫原性[J].中国生物制品学杂志,2013,26(1):1-4.
- [29]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.
- [30]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.
- [31]Merck&Co.Gardasil[Human papillomavirus quadrivalent(types 6,11,16,and 18)vaccine,recombinant].http://www.merck.com/product/usa/picirculars/g/gardasil/gardasil_pi.pdf(accessed June 02,2013).
- [32]GlaxoSmithKline.Cervarix[Human papillomavirus bivalent(types 16and 18)vaccine,recombinant].http://us.gsk.com/products/assets/us_cervarix.pdf(accessed June 02,2013).
- [33]Liu Q,Yan K,Feng Y,et al.A virus-like particle vaccine for coxsackievirus A16potently elicits neutralizing antibodies that protect mice against lethal challenge[J].Vaccine,2012,30:6642-6648.
- [34]Liu F,Liu Q,Cai Y,et al.Construction and characterization of an infectious clone of coxsackievirus A16[J].Virol J,2011,8:534.
- [35]Chen L,Mou X,Zhang Q,et al.Detection of human enterovirus 71and coxsackievirus A16in children with hand,foot and mouth disease in China[J].Mol Med Report,2012,5:1001-1004.
- [36]Ma E,Fung C,Yip S H,et al.Estimation of the basic reproduction number of enterovirus 71and coxsackievirus A16in hand,foot,and mouth disease outbreaks[J].Pediatr Infect Dis,2011,30:675-679.