Immune responses against enterovirus A71 infection: Implications for vaccine success.
enterovirus
enterovirus A71
epitope
immune response
vaccine
Journal
Reviews in medical virology
ISSN: 1099-1654
Titre abrégé: Rev Med Virol
Pays: England
ID NLM: 9112448
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
20
08
2018
revised:
24
05
2019
accepted:
31
05
2019
pubmed:
2
8
2019
medline:
9
4
2020
entrez:
2
8
2019
Statut:
ppublish
Résumé
Enterovirus A71 (EV-A71) from the Picornaviridae family is an important emerging pathogen causing hand, foot, and mouth disease (HFMD) outbreaks worldwide. EV-A71 also caused fatal neurological complications in young children especially in Asia. On the basis of seroepidemiological studies from many Asian countries, EV-A71 infection is very common. Children of very young age are particularly vulnerable. Large-scale epidemics that occur every 3 to 4 years are associated with accumulation of an immunologically naive younger population. Capsid proteins especially VP1 with the presence of major B- and T-cell epitopes are the most antigenic proteins. The nonstructural proteins mainly contribute to T-cell epitopes that induce cross-reactive immune responses against other enteroviruses. Dominant epitopes and their neutralization magnitudes differ in mice, rabbits, and humans. Neutralizing antibody is sufficient for immune protection, but poorer cellular immunity may lead to severe neurological complications and deaths. Some chemokines/cytokines are consistently found in severely ill patients, for example, IL-6, IL-10, IL-17A, MCP-1, IL-8, MIG, IP-10, IFN-γ, and G-CSF. An increase in white cell counts is a risk factor for severe HFMD. Recent clinical trials on EV-A71 inactivated vaccine showed >90% efficacy and a robust neutralization response that was protective, indicating neutralizing antibody correlates for protection. No protection against other enteroviruses was observed. A comprehensive understanding of the immune responses to EV-A71 infection will benefit the development of diagnostic tools, potential therapeutics, and subunit vaccine candidates. Future development of a multivalent enterovirus vaccine will require knowledge of correlates of protection, understanding of cross-protection and memory T-cell responses among enteroviruses.
Substances chimiques
Viral Vaccines
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2073Informations de copyright
© 2019 John Wiley & Sons, Ltd.
Références
Brown BA, Pallansch MA. Complete nucleotide sequence of enterovirus 71 is distinct from poliovirus. Virus Res. 1995;39:195-205.
Chan YF, Sam IC, Wee KL, AbuBakar S. Enterovirus 71 in Malaysia: a decade later. Neurol Asia. 2011;16:1-15.
Wang YF, Chou CT, Lei HY, et al. A mouse-adapted enterovirus 71 strain causes neurological disease in mice after oral infection. J Virol. 2004;78(15):7916-7924.
He Y, Ong KC, Gao Z, et al. Tonsillar crypt epithelium is an important extra-central nervous system site for viral replication in EV71 encephalomyelitis. Am J Pathol. 2014;184(3):714-720.
Chen CS, Yao YC, Lin SC, et al. Retrograde axonal transport: a major transmission route of enterovirus 71 in mice. J Virol. 2007;81(17):8996-9003.
Wong SS, Yip CC, Lau SK, Yuen KY. Human enterovirus 71 and hand, foot and mouth disease. Epidemiol Infect. 2010;138(8):1071-1089.
Cheng HY, Huang YC, Yen TY, et al. The correlation between the presence of viremia and clinical severity in patients with enterovirus 71 infection: a multi-center cohort study. BMC Infect Dis. 2014;14(1):417.
Chung PW, Huang YC, Chang LY, Lin TY, Ning HC. Duration of enterovirus shedding in stool. J Microbiol Immunol Infect. 2001;34:167-170.
Wu Q, Fu X, Jiang L, et al. Prevalence of enteroviruses in healthy populations and excretion of pathogens in patients with hand, foot, and mouth disease in a highly endemic area of southwest China. PLoS ONE. 2017;12(7):e0181234.
Li J, Lin C, Qu M, et al. Excretion of enterovirus 71 in persons infected with hand, foot and mouth disease. Virol J. 2013;10(1):31.
Perez-Velez CM, Anderson MS, Robinson CC, et al. Outbreak of neurologic enterovirus type 71 disease: a diagnostic challege. Clin Infect Dis. 2007;45(8):950-957.
Wang SM, Lei HY, Su LY, et al. Cerebrospinal fluid cytokines in enterovirus 71 brain stem encephalits and echovirus meningitis infections of varying severity. Clin Microbiol Infect. 2007;13(7):677-682.
Koh WM, Bogich T, Siegel K, et al. The epidemiology of hand, foot and mouth disease in Asia: a systematic review and analysis. Pediatr Infect Dis J. 2016;35(10):e285-e300.
Aw-Yong KL, Sam IC, Koh MT, Chan YF. Causative agents of hand, foot and mouth disease in University Malaya Medical Centre, Kuala Lumpur, Malaysia in 2012-2013. Trop Biomed. 2017;34:240-248.
Chan YF, Wee KL, Chiam CW, et al. Comparative genetic analysis of VP4, VP1 and 3D gene regions of enterovirus 71 and coxsackievirus A16 circulating in Malaysia between 1997-2008. Trop Biomed. 2012;29:451-466.
Chang LY, King CC, Hsu KH, et al. Risk factors of enterovirus 71 infection and associated hand, foot, and mouth disease/herpangina in children during an epidemic in Taiwan. Pediatrics. 2002;109(6):e88.
Chan LG, Parashar UD, Lye MS, et al. Deaths of children during an outbreak of hand, foot, and mouth disease in Sarawak, Malaysia: clinical and pathological characteristics of the disease. For the Outbreak Study Group. Clin Infect Dis. 2000;31(3):678-683.
Ong KC, Wong KT. Understanding enterovirus 71 neuropathogenesis and its impact on other neurotropic enteroviruses. Brain Pathol. 2015;25:614-624.
Yip CC, Lau SK, Woo PC, Yuen KY. Human enterovirus 71 epidemics: what's next? Emerg Health Threats J. 2013;6(1):19780.
Ooi MH, Wong SC, Lewthwaite P, Cardosa MJ, Solomon T. Clinical feactures, diagnosis, and management of enterovirus 71. Lancet Neurol. 2010;9:1097-1105.
Chang LY, Hsia SH, Wu CT, et al. Outcome of enterovirus 71 infections with or without stage-based management: 1998 to 2002. Pediatr Infect Dis J. 2004;23(4):327-332.
Chua KB, Kasri AR. Hand foot and mouth disease due to enterovirus 71 in Malaysia. Virol Sin. 2011;26:221-228.
Cardosa MJ, Krishnan S, Tio PH, Perera D, Wong SC. Isolation of subgenus B adenovirus during a fatal outbreak of enterovirus 71-associated hand, foot, and mouth disease in Sibu, Sarawak. Lancet. 1999;354:987-991.
Ho M. Enterovirus 71: the virus, its infections and outbreaks. J Microbiol Immunol Infect. 2000;33:205-216.
Lu CY, Lee CY, Kao CL, et al. Incidence and case-fatality rates resulting from the 1998 enterovirus 71 outbreak in Taiwan. J Med Virol. 2002;67(2):217-223.
Sabanathan S, Thwaites L, Wills B, Qui PT, van Doorn HR. Enterovirus 71 related severe hand, foot and mouth disease outbreaks in South-East Asia: current situation and ongoing challenges. J Epidemiol Community Health. 2014;68(6):500-502.
Gao LD, Hu SX, Zhang H, et al. Correlation analysis of EV71 detection and case severity in hand, foot, and mouth disease in the Hunan Province of China. PLoS ONE. 2014;9(6):e100003.
Xing W, Liao Q, Viboud C, et al. Hand, foot, and mouth disease in China, 2008-12: an epidemiological study. Lancet Infect Dis. 2014;14(4):308-318.
Zhang J, Sun J, Chang Z, Zhang W, Wang Z, Feng Z. Characterization of hand, foot, and mouth disease in China between 2008 and 2009. Biomed Envirion Sci. 2011;24:214-221.
Koh WM, Badaruddin H, La H, Chen MI, Cook AR. Severity and burden of hand, foot and mouth disease in Asia: a modelling study. BMJ Glob Health. 2018;3:e000442.
Ang LW, Phoon MC, Wu Y, Cutter J, James L, Chow VT. The changing seroepidemiology of enterovirus 71 infection among children and adolescents in Singapore. BMC Infect Dis. 2011;11:270.
Ang LW, Tay J, Phoon MC, et al. Seroepidemiology of coxsackievirus A6, coxsackievirus A16, and enterovirus 71 infections among children and adolescents in Singapore, 2008-2010. PLoS ONE. 2015;10(5):e0127999.
Ooi EE, Phoon MC, Ishak B, Chan SH. Seroepidemiology of human enterovirus 71, Singapore. Emerg Infect Dis. 2002;8:995-997.
Horwood PF, Andronico A, Tarantola A, et al. Seroepidemiology of human enterovirus 71 infection among children, Cambodia. Emerg Infect Dis. 2016;22(1):92-95.
Tran CB, Nguyen HT, Phan HT, et al. The seroprevalence and seroincidence of enterovirus71 infection in infants and children in Ho Chi Minh City, Viet Nam. PLoS ONE. 2011;6(7):e21116.
Linsuwanon P, Puenpa J, Huang SW, et al. Epidemiology and seroepidemiology of human enterovirus 71 among Thai populations. J Biomed Sci. 2014;21(1):16.
Mizuta K, Aoki Y, Suto A, et al. Cross-antigenicity among EV71 strains from different genogroups isolated in Yamagata, Japan, between 1990 and 2007. Vaccine. 2009;27(24):3153-3158.
NikNadia N, Sam IC, Khaidir N, et al. Risk factors for enterovirus A71 seropositivity in rural indigenous populations in West Malaysia. PLoS ONE. 2016;11(2):e0148767.
NikNadia N, Sam IC, Rampal S, et al. Cyclical patterns of hand, foot and mouth disease caused by enterovirus A71 in Malaysia. PLoS Negl Trop Dis. 2016;10(3):e0004562.
Gomes Mde L, de Castro CM, Oliveira MJ, da Silva EE. Neutralizing antibodies to enterovirus 71 in Belem, Brazil. Mem Inst Oswaldo Cruz. 2002;97(1):47-49.
Luchs A, Cilli A, Russo DH, Costa FF, Carmona Rde C, Timenetsky MC. Evaluation of enterovirus 71 immune status in Sao Paulo state, Brazil. Rev Inst Med Trop Sao Paulo. 2010;52:339-341.
Ji H, Li L, Liu Y, et al. Seroepidemiology of human enterovirus 71 and coxsackievirus A16 in Jiangsu province, China. Virol J. 2012;9(1):248.
Li W, Yi L, Su J, et al. Seroprevalence of human enterovirus 71 and coxsackievirus A16 in Guangdong, China, in pre- and post-2010 HFMD epidemic period. PLoS ONE. 2013;8(12):e80515.
Liu MY, Liu J, Lai W, et al. Characterization of enterovirus 71 infection and associated outbreak of hand, foot, and mouth disease in Shawo of China in 2012. Sci Rep. 2016;6(1):38451.
Ni H, Yi B, Yin J, et al. Epidemiological and etiological characteristics of hand, foot, and mouth disease in Ningbo, China, 2008-2011. J Clin Virol. 2012;54(4):342-348.
Wang JX, Zhu SL, Wang J, et al. Seroprevalence of enterovirus A71 and coxsackievirus A16 in healthy people in Shandong province, China. PLoS ONE. 2016;11(9):e0162373.
Yu H, Wang M, Chang H, et al. Prevalence of antibodies against enterovirus 71 in children from Lu'an City in Central China. Jpn J Infect Dis. 2011;64:528-532.
Zeng M, El Khatib NF, Tu S, et al. Seroepidemiology of enterovirus 71 infection prior to the 2011 season in children in Shanghai. J Clin Virol. 2012;53(4):285-289.
Zhang D, Chen Y, Chen X, He Z, Zhu X, Hao Y. Enterovirus 71 neutralizing antibodies seroepidemiological research among children in Guangzhou, China between 2014 and 2015: a cross-sectional study. Int J Environ Res Public Health. 2017;14:319.
Zhu FC, Liang ZL, Meng FY, et al. Retrospective study of the incidence of HFMD and seroepidemiology of antibodies against EV71 and CoxA16 in prenatal women and their infants. PLoS ONE. 2012;7(5):e37206.
Zhu Z, Zhu S, Guo X, et al. Retrospective seroepidemiology indicated that human enterovirus 71 and coxsackievirus A16 circulated wildly in central and southern China before large-scale outbreaks from 2008. Virol J. 2010;7(1):300.
Diedrich S, Weinbrecht A, Schreier E. Seroprevalence and molecular epidemiology of enterovirus 71 in Germany. Arch Virol. 2009;154:1139-1142.
Rabenau HF, Richter M, Doerr HW. Hand, foot and mouth disease: seroprevalence of coxsackie A16 and enterovirus 71 in Germany. Med Microbiol Immunol. 2010;199:45-51.
Akhmadishina LV, Eremeeva TP, Trotsenko OE, Ivanova OE, Mikhailov MI, Lukashev AN. Seroepidemiology and molecular epidemiology of enterovirus 71 in Russia. PLoS ONE. 2014;9:e97404.
Luo ST, Chiang PS, Chao AS, et al. Enterovirus 71 maternal antibodies in infants, Taiwan. Emerg Infect Dis. 2009;15(4):581-584.
Yang B, Wu P, Wu JT, et al. Seroprevalence of enterovirus 71 antibody among children in China: a systematic review and meta-analysis. Pediatr Infect Dis J. 2015;34(12):1399-1406.
Lee MS, Chiang PS, Luo ST, et al. Incidence rates of enterovirus 71 infections in young children during a nationwide epidemic in Taiwan, 2008-09. PLoS Negl Trop Dis. 2012;6(2):e1476.
Lin H, Sun L, Lin J, et al. Protective effect of exclusive breastfeeding against hand, foot and mouth disease. BMC Infect Dis. 2014;14(1):645.
Yang C, Deng C, Wan J, Zhu L, Leng Q. Neutralizing antibody response in the patients with hand, foot and mouth disease to enterovirus 71 and its clinical implications. Virol J. 2011;8(1):306.
Xu F, Yan Q, Wang H, et al. Performance of detecting IgM antibodies against enterovirus 71 for early diagnosis. PLoS ONE. 2010;5(6):e11388.
Wang SY, Lin TL, Chen HY, Lin TS. Early and rapid detection of enterovirus 71 infection by an IgM-capture ELISA. J Virol Methods. 2004;119:37-43.
Chang LY, Hsiung CA, Lu CY, et al. Status of cellular rather than humoral immunity is correlated with clinical outcome of enterovirus 71. Pediatr Res. 2006;60(4):466-471.
Li GM, Chiu C, Wrammert J, et al. Pandemic H1N1 influenza vaccine induces a recall response in humans that favors broadly cross-reactive memory B cells. Proc Natl Acad Sci U S A. 2012;109(23):9047-9052.
Morbach H, Eichhorn EM, Liese JG, Girschick HJ. Reference values for B cell subpopulations from infancy to adulthood. Clin Exp Immunol. 2010;162(2):271-279.
Huang KY, Lin JJ, Chiu CH, et al. A potent virus-specific antibody-secreting cell response to acute enterovirus 71 infection in children. J Infect Dis. 2015;212(5):808-817.
Gao F, Wang YP, Mao QY, et al. Enterovirus 71 viral capsid protein linear epitopes: identification and characterization. Virol J. 2012;9(1):26.
Liu CC, Chou AH, Lien SP, et al. Identification and characterization of a cross-neutralization epitope of enterovirus 71. Vaccine. 2011;29(26):4362-4372.
Zhang J, Huang H, Xu L, Lou C, Pan M. Screening and identification of linear B cell epitopes within the nonstructural proteins of enterovirus 71. Viral Immunol. 2019;32(2):84-88.
Foo DG, Alonso S, Phoon MC, Ramachandran NP, Chow VT, Poh CL. Identification of neutralizing linear epitopes from the VP1 capsid protein of enterovirus 71 using synthetic peptides. Virus Res. 2007;125(1):61-68.
Aw-Yong KL, Sam IC, Koh MT, Chan YF. Immunodominant IgM and IgG epitopes recognized by antibodies induced in enterovirus A71-associated hand, foot and mouth disease patients. PLoS ONE. 2016;11:e0165659.
Zhang H, Song Z, Yu H, et al. Genome-wide linear B-cell epitopes of enterovirus 71 in a hand, foot and mouth disease (HFMD) population. J Clin Virol. 2018;105:41-48.
Cello J, Samuelson A, Stalhandske P, Svennerholm B, Jeansson S, Forsgren M. Identification of group-common linear epitopes in structural and nonstructural proteins of enteroviruses by using synthetic peptides. J Clin Microbiol. 1993;31:911-916.
Sivasamugham LA, Cardosa MJ, Tan WS, Yusoff K. Recombinant Newcastle disease virus capsids displaying enterovirus 71 VP1 fragment induce a strong immune response in rabbits. J Med Virol. 2006;78(8):1096-1104.
Foo DG, Alonso S, Chow VT, Poh CL. Passive protection against lethal enterovirus 71 infection in newborn mice by neutralizing antibodies elicited by a synthetic peptide. Microbes Infect. 2007;9(11):1299-1306.
NikNadia N, Tan CW, Ong KC, Sam IC, Chan YF. Identification and characterization of neutralization epitopes at VP2 and VP1 of enterovirus A71. J Med Virol. 2018;90(6):1164-1167.
Cello J, Strannegard O, Svennerholm B. A study of the cellular immune response to enteroviruses in humans: identification of cross-reactive T cell epitopes on the structural proteins of enteroviruses. J Gen Virol. 1996;77(9):2097-2108.
Foo DG, Macary PA, Alonso S, Poh CL. Identification of human CD4 T-cell epitopes on the VP1 capsid protein of enterovirus 71. Viral Immunol. 2008;21(2):215-224.
Wei R, Yang C, Zeng M, et al. A dominant EV71-specific CD4+ T cell epitope is highly conserved among human enteroviruses. PLoS ONE. 2012;7(12):e51957.
Tan S, Tan X, Sun X, et al. VP2 dominated CD4+ T cell responses against enterovirus 71 and cross-reactivity against coxsackievirus A16 and polioviruses in a healthy population. J Immunol. 2013;191(4):1637-1647.
Dang S, Gao N, Li Y, et al. Dominant CD4-dependent RNA-dependent RNA polymerase-specific T-cell responses in children acutely infected with human enterovirus 71 and healthy adult controls. Immunology. 2014;142(1):89-100.
Minor PD, Ferguson M, Evans DM, Almond JW, Icenogle JP. Antigenic structure of polioviruses of serotypes 1, 2 and 3. J Gen Virol. 1986;67:1283-1291.
Wang SM, Chen IC, Su LY, Huang KJ, Lei HY, Liu CC. Enterovirus 71 infection of monocytes with antibody-dependent enhancement. Clin Vaccine Immunol. 2010;17(10):1517-1523.
Han JF, Cao RY, Deng YQ, et al. Antibody dependent enhancement infection of enterovirus 71 in vitro and in vivo. Virol J. 2011;8(1):106.
Cao RY, Dong DY, Liu RJ, et al. Human IgG subclasses against enterovirus type 71: neutralization versus antibody dependent enhancement of infection. PLoS ONE. 2013;8(5):e64024.
Yang KD, Yang MY, Li CC, et al. Altered cellular but not humoral reactions in children with complicated enterovirus 71 infections in Taiwan. J Infect Dis. 2001;183(6):850-856.
Wang SM, Lei HY, Huang KJ, et al. Pathogenesis of enterovirus 71 brainstem encephalitis in pediatric patients: roles of cytokines and cellular immune activation in patients with pulmonary edema. J Infect Dis. 2003;188(4):564-570.
Li S, Cai C, Feng J, et al. Peripheral T lymphocyte subset imbalances in children with enterovirus 71-induced hand, foot and mouth disease. Virus Res. 2014;180:84-91.
Wu J, Cui D, Yang X, et al. Increased frequency of circulating follicular helper T cells in children with hand, foot, and mouth disease caused by enterovirus 71 infection. J Immunol Res. 2014;2014:651872.
Lin TY, Chang LY, Huang YC, Hsu KH, Chiu CH, Yang KD. Different proinflammatory reactions in fatal and non-fatal enterovirus 71 infections: implications for early recognition and therapy. Acta Paediatr. 2002;91(6):632-635.
Lin TY, Hsia SH, Huang YC, Wu CT, Chang LY. Proinflammatory cytokine reactions in enterovirus 71 infections of the central nervous system. Clin Infect Dis. 2003;36(3):269-274.
Griffiths MJ, Ooi MH, Wong SC, et al. In enterovirus 71 encephalitis with cardio-respiratory compromise, elevated interleukin 1beta, interleukin 1 receptor antagonist, and granulocyte colony-stimulating factor levels are markers of poor prognosis. J Infect Dis. 2012;206(6):881-892.
Chen Z, Li R, Xie Z, Huang G, Yuan Q, Zeng J. IL-6, IL-10 and IL-13 are associated with pathogenesis in children with enterovirus 71 infection. Int J Clin Exp Med. 2014;7(9):2718-2723.
Zheng W, Shi H, Chen Y, Xu Z, Chen J, Jin L. Alteration of serum high-mobility group protein 1 (HMGB1) levels in children with enterovirus 71-induced hand, foot, and mouth disease. Medicine. 2017;96(17):e6764.
Zhang Y, Liu H, Wang L, et al. Comparative study of the cytokine/chemokine response in children with differing disease severity in enterovirus 71-induced hand, foot, and mouth disease. PLoS ONE. 2013;8(6):e67430.
Ye N, Gong X, Pang LL, et al. Cytokine responses and correlations thereof with clinical profiles in children with enterovirus 71 infections. BMC Infect Dis. 2015;15(1):225.
Wang CF, Cai CY, Li SX, Zheng JF, Ye B, Chen ZM. Cytokine response differences in enterovirus 71 and other enterovirus-caused hand foot and mouth disease complicated with aseptic meningitis. HK J Paediatr (New Series). 2017;22:80-87.
Marron MP, Raffel LJ, Garchon HJ, et al. Insulin-dependent diabetes mellitus (IDDM) is associated with CTLA4 polymorphisms in multiple ethnic groups. Hum Mol Genet. 1997;6(8):1275-1282.
Li MZ, Pang LL, Bai AY, et al. Association of chemotactic chemokine ligand 5 polymorphisms with the risk of developing severe enterovirus 71 infection. Am J Trop Med Hyg. 2015;93(4):709-713.
Peck A, Mellins ED. Plasticity of T-cell phenotype and function: the T helper type 17 example. Immunology. 2010;129(2):147-153.
Fu D, Li CR, He YX, et al. Changes of immune function in patients with enterovirus 71 infection. Zhonghua Er Ke Za Zhi. 2009;47(11):829-834. (Article in Chinese).
Ma CS, Suryani S, Avery DT, et al. Early commitment of naive human CD4(+) T cells to the T follicular helper (T (FH)) cell lineage is induced by IL-12. Immunol Cell Biol. 2009;87(8):590-600.
Weber CA, Mehta PJ, Ardito M, Moise L, Martin B, De Groot AS. T cell epitope: friend or foe? Immunogenicity of biologics in context. Adv Drug Deliv Rev. 2009;61:965-976.
Jin Y, Zhang R, Wu W, Duan G. Antiviral and inflammatory cellular signaling associated with enterovirus 71 infection. Viruses. 2018;10:E155.
Pathinayake PS, Hsu AC, Wark PA. Innate immunity and immune evasion by enterovirus 71. Viruses. 2015;7:6613-6630.
Harris KG, Coyne CB. Enter at your own risk: how enteroviruses navigate the dangerous world of pattern recognition receptor signaling. Cytokine. 2013;63(3):230-236.
Cox JA, Hiscox JA, Solomon T, Ooi MH, Ng LFP. Immunopathogenesis and virus-host interactions of enterovirus 71 in patients with hand, foot and mouth disease. Front Microbiol. 2017;8:2249.
Zhang Y, Li J, Li Q. Immune evasion of enteroviruses under innate immune monitoring. Front Microbiol. 2018;9:1866.
Wang W, Li W, Yang X, et al. Interleukin-8 is elevated in severe hand, foot, and mouth disease. J Infect Dev Ctries. 2014;8:94-100.
Wang SM, Lei HY, Yu CK, Wang JR, Su IJ, Liu CC. Acute chemokine response in the blood and cerebrospinal fluid of children with enterovirus 71-associated brainstem encephalitis. J Infect Dis. 2008;198(7):1002-1006.
Zhao MQ, Wang LH, Lian GW, et al. Characterization of lymphocyte subsets in peripheral blood cells of children with EV71 infection. J Microbiol Immunol Infect. 2019. https://doi.org/10.1016/j.jmii.2019.03.001
Chen J, Tong J, Liu H, et al. Increased frequency of Th17 cells in the peripheral blood of children infected with enterovirus 71. J Med Virol. 2012;84(5):763-767.
Zeng M, Zheng X, Wei R, et al. The cytokine and chemokine profiles in patients with hand, foot and mouth disease of different severities in Shanghai, China, 2010. PLoS Negl Trop Dis. 2013;7(12):e2599.
Zhang SY, Xu MY, Xu HM, et al. Immunologic characterization of cytokine responses to enterovirus 71 and coxsackievirus A16 infection in children. Medicine. 2015;94(27):e1137.
Wang J, Pu J, Liu L, et al. Clinical and associated immunological manifestations of HFMD caused by different viral infections in children. Glob Pediatr Health. 2016;3:2333794X16643723.
Teo FMS, Nyo M, Wong AA, et al. Cytokine and chemokine profiling in patients with hand, foot and mouth disease in Singapore and Malaysia. Sci Rep. 2018;8(1):4087.
Wang SM, Lei HY, Huang MC, et al. Modulation of cytokine production by intravenous immunoglobulin in patients with enterovirus 71-associated brainstem encephalitis. J Clin Virol. 2006;37(1):47-52.
Shao J, Zhang J, Wu X, et al. Comparing the primary and recall immune response induced by a new EV71 vaccine using systems biology approaches. PLoS ONE. 2015;10(10):e0140515.
Chang LY, Lin TY, Hsu KH, et al. Clinical features and risk factors of pulmonary oedema after enterovirus-71-related hand, foot, and mouth disease. Lancet. 1999;354(9191):1682-1686.
Huang HI, Weng KF, Shih SR. Viral and host factors that contribute to pathogenicity of enterovirus 71. Future Microbiol. 2012;7(4):467-479.
Machida K, Cheng KT, Sung VM, Levine AM, Foung S, Lai MM. Hepatitis C virus induces toll-like receptor 4 expression, leading to enhanced production of beta interferon and interleukin-6. J Virol. 2006;80(2):866-874.
Khong WX, Foo DG, Trasti SL, Tan EL, Alonso S. Sustained high levels of interleukin-6 contribute to the pathogenesis of enterovirus 71 in a neonate mouse model. J Virol. 2011;85:3067-3076.
Yuan J, Liu Z, Lim T, et al. CXCL10 inhibits viral replication through recruitment of natural killer cells in coxsackievirus B3-induced myocarditis. Circ Res. 2009;104(5):628-638.
Shen FH, Tsai CC, Wang LC, et al. Enterovirus 71 infection increases expression of interferon-gamma-inducible protein 10 which protects mice by reducing viral burden in multiple tissues. J Gen Virol. 2013;94(Pt_5):1019-1027.
Boehm U, Klamp T, Groot M, Howard JC. Cellular responses to interferon-gamma. Annu Rev Immunol. 1997;15:749-795.
Biondillo DE, Konicek SA, Iwamoto GK. Interferon-gamma regulation of interleukin 6 in monocytic cells. Am J Physiol. 1994;267:L564-L568.
Martin S, Maruta K, Burkart V, Gillis S, Kolb H. IL-1 and IFN-gamma increase vascular permeability. Immunology. 1988;64:301-305.
Ramshaw IA, Ramsay AJ, Karupiah G, Rolph MS, Mahalingam S, Ruby JC. Cytokines and immunity to viral infections. Immunol Rev. 1997;159:119-135.
Rasti M, Khanbabaei H, Teimoori A. An update on enterovirus 71 infection and interferon type I response. Rev Med Virol. 2019;29(1):e2016.
Lee AJ, Ashkar AA. The dual nature of type I and type II interferons. Front Immunol. 2018;9:2061.
Mogensen TH, Paludan SR. Molecular pathways in virus-induced cytokine production. Microbiol Mol Biol Rev. 2001;65(1):131-150.
Chew SP, Chong SL, Barbier S, Matthew A, Lee JH, Chan YH. Risk factors for severe hand foot mouth disease in Singapore: a case control study. BMC Infect Dis. 2015;15:486.
Tecchio C, Micheletti A, Cassatella MA. Neutrophil-derived cytokines: facts beyond expression. Front Immunol. 2014;5:508.
Gabriel C, Her Z, Ng LF. Neutrophils: Neglected players in viral diseases. DNA Cell Biol. 2013;32:665-675.
Galani IE, Andreakos E. Neutrophils in viral infections: current concepts and caveats. J Leukoc Biol. 2015;98:557-564.
Jenne CN, Wong CH, Zemp FJ, et al. Neutrophils recruited to sites of infection protect from virus challenge by releasing neutrophil extracellular traps. Cell Host Microbe. 2013;13(2):169-180.
Ooi MH, Wong SC, Mohan A, et al. Identification and validation of clinical predictors for the risk of neurological involvement in children with hand, foot, and mouth disease in Sarawak. BMC Infect Dis. 2009;9(1):3.
Xing J, Liu D, Shen S, et al. Pathologic studies of fatal encephalomyelitis in children caused by enterovirus 71. Am J Clin Pathol. 2016;146(1):95-106.
Pang L, Gong X, Liu N, et al. A polymorphism in melanoma differentiation-associated gene 5 may be a risk factor for enterovirus 71 infection. Clin Microbiol Infect. 2014;20(10):O711-O717.
Li JA, Chen ZB, Lv TG, Han ZL. Genetic polymorphism of CCL2-2518, CXCL10-201, IL8+781 and susceptibility to severity of enterovirus-71 infection in a Chinese population. Inflamm Res. 2014;63:549-556.
Zhao N, Chen HL, Chen ZZ, Li J, Chen ZB. IL-10-592 polymorphism is associated with IL-10 expression and severity of enterovirus 71 infection in chinese children. J Clin Virol. 2017;95:42-46.
Xu D, Li J, Huang X, Lin A, Gai Z, Chen Z. Impact of IL-8-251A/T gene polymorphism on severity of disease caused by enterovirus 71 infection. Arch Virol. 2016;161(1):203-207.
Yuan A, Li J, Liu P, et al. Association of interleukin-6-572C/G gene polymorphism and serum or cerebrospinal fluid interleukin-6 level with enterovirus 71 encephalitis in Chinese Han patients with hand, foot, and mouth disease. Inflammation. 2015;38(2):728-735.
Han ZL, Li JA, Chen ZB. Genetic polymorphism of CCL2-2510 and susceptibility to enterovirus 71 encephalitis in a Chinese population. Arch Virol. 2014;159(9):2503-2507.
Wang SM, Ho TS, Shen CF, Liu CC. Enterovirus 71, one virus and many stories. Pediatr Neonatol. 2008;49:113-115.
Cao R, Han J, Deng Y, Yu M, Qin E, Qin C. Presence of high-titer neutralizing antibodies against enterovirus 71 in intravenous immunoglobulin manufactured from Chinese donors. Clin Infect Dis. 2010;50:125-126.
Jolles S, Sewell WA, Misbah SA. Clinical uses of intravenous immunoglobulin. Clin Exp Immunol. 2005;142:1-11.
Ng Q, He F, Kwang J. Recent progress towards novel EV71 anti-therapeutics and vaccines. Viruses. 2015;7:6441-6457.
Ameratunga R, Sinclair J, Kolbe J. Increased risk of adverse events when changing intravenous immunoglobulin preparations. Clin Exp Immunol. 2004;136:111-113.
Chea S, Cheng YB, Chokephaibulkit K, et al. Workshop on use of intravenous immunoglobulin in hand, foot and mouth disease in Southeast Asia. Emerg Infect Dis. 2015;21:e140992.
Chang GH, Luo YJ, Wu XY, Si BY, Lin L, Zhu QY. Monoclonal antibody induced with inactived EV71-Hn2 virus protects mice against lethal EV71-Hn2 virus infection. Virol J. 2010;7:106.
Deng YQ, Ma J, Xu LJ, et al. Generation and characterization of a protective mouse monoclonal antibody against human enterovirus 71. Appl Microbiol Biotechnol. 2015;99(18):7663-7671.
Kiener TK, Jia Q, Lim XF, et al. Characterization and specificity of the linear epitope of the enterovirus 71 VP2 protein. Virol J. 2012;9(1):55.
Kiener TK, Jia Q, Meng T, Chow VT, Kwang J. A novel universal neutralizing monoclonal antibody against enterovirus 71 that targets the highly conserved “knob” region of VP3 protein. PLoS Negl Trop Dis. 2014;8:e2895.
Li X, Mao C, Ma S, et al. Generation of neutralizing monoclonal antibodies against enterovirus 71 using synthetic peptides. Biochem Biophys Res Commun. 2009;390(4):1126-1128.
Lim XF, Jia Q, Khong WX, et al. Characterization of an isotype-dependent monoclonal antibody against linear neutralizing epitope effective for prophylaxis of enterovirus 71 infection. PLoS ONE. 2012;7(1):e29751.
Liu ML, Lee YP, Wang YF, et al. Type I interferons protect mice against enterovirus 71 infection. J Gen Virol. 2005;86(12):3263-3269.
Li Z, Wang H, Chen Y, et al. Interleukin-18 protects mice from enterovirus 71 infection. Cytokine. 2017;96:132-137.
Ch'ng WC, Saw WT, Yusoff K, Shafee N. Immunogenicity of a truncated enterovirus 71 VP1 protein fused to a Newcastle disease virus nucleocapsid protein fragment in mice. Acta Virol. 2011;55:227-233.
Wang M, Jiang S, Wang Y. Recombinant VP1 protein expressed in Pichia pastoris induces protective immune responses against EV71 in mice. Biochem Biophys Res Commun. 2013;430:387-393.
Lin YL, Yu CI, Hu YC, et al. Enterovirus type 71 neutralizing antibodies in the serum of macaque monkeys immunized with EV71 virus-like particles. Vaccine. 2012;30(7):1305-1312.
Tung WS, Bakar SA, Sekawi Z, Rosli R. DNA vaccine constructs against enterovirus 71 elicit immune response in mice. Genet Vaccines Ther. 2007;5(1):6.
Liu JN, Wang W, Duo JY, et al. Combined peptides of human enterovirus 71 protect against virus infection in mice. Vaccine. 2010;28(46):7444-7451.
Chiu CH, Chu C, He CC, Lin TY. Protection of neonatal mice from lethal enterovirus 71 infection by maternal immunization with attenuated Salmonella enterica serovar Typhimurium expressing VP1 of enterovirus 71. Microbes Infect. 2006;8:1671-1678.
Arita M, Nagata N, Iwata N, et al. An attenuated strain of enterovirus 71 belonging to genotype a showed a broad spectrum of antigenicity with attenuated neurovirulence in cynomolgus monkeys. J Virol. 2007;81(17):9386-9395.
Dong C, Liu L, Zhao H, et al. Immunoprotection elicited by an enterovirus type 71 experimental inactivated vaccine in mice and rhesus monkeys. Vaccine. 2011;29(37):6269-6275.
Bek EJ, Hussain KM, Phuektes P, et al. Formalin-inactivated vaccine provokes cross-protective immunity in a mouse model of human enterovirus 71 infection. Vaccine. 2011;29(29-30):4829-4838.
Ong KC, Devi S, Cardosa MJ, Wong KT. Formaldehyde-inactivated whole-virus vaccine protects a murine model of enterovirus 71 encephalomyelitis against disease. J Virol. 2010;84:661-665.
Fang CY, Liu CC. Recent development of enterovirus A vaccine candidates for the prevention of hand, foot, and mouth disease. Expert Rev Vaccines. 2018;17:819-831.
Zhang D, Lu J, Lu J. Enterovirus 71 vaccine: close but still far. Int J Infect Dis. 2010;14:e739-e743.
Chong P, Liu CC, Chow YH, Chou AH, Klein M. Review of enterovirus 71 vaccines. Clin Infect Dis. 2015;60:797-803.
Li YX, Zhao H, Cao RY, et al. Recombinant tandem multi-linear neutralizing epitopes of human enterovirus 71 elicited protective immunity in mice. Virol J. 2014;11(1):79.
Zhao M, Bai Y, Liu W, et al. Immunization of N terminus of enterovirus 71 VP4 elicits cross-protective antibody responses. BMC Microbiol. 2013;13(1):287.
Li R, Liu L, Mo Z, et al. An inactivated enterovirus 71 vaccine in healthy children. N Engl J Med. 2014;370(9):829-837.
Liu L, Mo Z, Liang Z, et al. Immunity and clinical efficacy of an inactivated enterovirus 71 vaccine in healthy Chinese children: a report of further observations. BMC Med. 2015;13(1):226.
Zhu F, Xu W, Xia J, et al. Efficacy, safety, and immunogenicity of an enterovirus 71 vaccine in China. N Engl J Med. 2014;370(9):818-828.
Hu Y, Zeng G, Chu K, et al. Five-year immunity persistence following immunization with inactivated enterovirus 71 type (EV71) vaccine in healthy children: a further observation. Hum Vaccin Immunother. 2018;14(6):1517-1523.
Zhu FC, Meng FY, Li JX, et al. Efficacy, safety, and immunology of an inactivated alum-adjuvant enterovirus 71 vaccine in children in China: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2013;381(9882):2024-2032.
Wei M, Meng F, Wang S, et al. 2-year efficacy, immunogenicity, and safety of Vigoo enterovirus 71 vaccine in healthy Chinese children: a randomized open-label study. J Infect Dis. 2017;215(1):56-63.
China Food and Drug Administration. The Food and Drug Administration approved the production of enterovurs 71 inactivated vaccine. http://samr.cfda.gov.cn/WS01/CL0051/136853.html. 2015. Accessed February 23, 2019. (Article in Chinese)
China Food and Drug Administration. Announcement of approved drugs by the Food and Drug Administration (no. 4, 2016). http://samr.cfda.gov.cn/WS01/CL0087/142000.html. 2016. Accessed February 23, 2019. (Article in Chinese)
Hubei Provincial Drug Administration. Announcement of Hubei province drug registration review approval report in 2016 issued by Provincial Food and Drug Administration Office. http://www.hubfda.gov.cn/zxbw/gztz/eslb/30764.htm. 2017. Accessed February 23, 2019. (Article in Chinese)
Zhu W, Jin P, Li JX, Zhu FC, Liu P. Correlates of protection for inactivated enterovirus 71 vaccine: the analysis of immunological surrogate endpoints. Expert Rev Vaccines. 2017;16(9):945-949.
Liu L, Zhang Y, Wang J, et al. Study of the integrated immune response induced by an inactivated EV71 vaccine. PLoS ONE. 2013;8(1):e54451.
Zhang Y, Wang L, Liao Y, et al. Similar protective immunity induced by an inactivated enterovirus 71 (EV71) vaccine in neonatal rhesus macaques and children. Vaccine. 2015;33(46):6290-6297.
Ter Horst R, Jaeger M, Smeekens SP, et al. Host and environmental factors influencing individual human cytokine responses. Cell. 2016;167(4):1111-1124.
Huang J, Liao Q, Ooi MH, et al. Epidemiology of recurrent hand, foot and mouth disease, China, 2008-2015. Emerg Infect Dis. 2018;24(3):432.
Takahashi S, Liao Q, Van Boeckel TP, et al. Hand, foot, and mouth disease in China: modeling epidemic dynamics of enterovirus serotypes and implications for vaccination. PLoS Med. 2016;13(2):e1001958.