Please wait a minute...

Frontiers of Medicine

Front Med    2013, Vol. 7 Issue (1) : 111-121
Progress on the research and development of human enterovirus 71 (EV71) vaccines
Zhenglun Liang, Qunying Mao, Fan Gao, Junzhi Wang()
National Institutes for Food and Drug Control, Beijing 100050, China
Download: PDF(219 KB)   HTML
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks

Enterovirus 71 (EV71) infections, which can cause severe complications, have become one of the serious public health issues in the Western Pacific region and China. To date, a number of pharmaceutical companies and institutes have initiated the research and development of EV71 vaccines as a countermeasure. As is the case with innovative vaccine development, there are several critical bottlenecks in EV71 vaccine development that must be overcome before the clinical trials, including the selection of vaccine strain, standardization of the procedure for quantifying neutralizing antibody (NTAb) and antigen, establishment and application of a reference standard and biological standards, development of animal models for the evaluation of protective efficacy, and identification of the target patient population. To tackle these technical obstacles, researchers in Mainland of China have conducted a series of studies concerning the screening of vaccine strains and the establishment of criteria, biological standards and detection methods, thereby advancing EV71 vaccine development. This review summarizes recent worldwide progress on the quality control and evaluation of EV71 vaccines.

Keywords enterovirus 71 (EV71)      hand, foot, and mouth disease (HFMD)      vaccine     
Corresponding Author(s): Wang Junzhi,   
Issue Date: 05 March 2013
 Cite this article:   
Zhenglun Liang,Qunying Mao,Fan Gao, et al. Progress on the research and development of human enterovirus 71 (EV71) vaccines[J]. Front Med, 2013, 7(1): 111-121.
E-mail this article
E-mail Alert
Articles by authors
Zhenglun Liang
Qunying Mao
Fan Gao
Junzhi Wang
Fig.1  Incidence of HFMD (cumulative number, as well as severe and fatal cases) in China (Mainland and Taiwan) from 1998 to 2012. Data Source:; (Accessed on July 2, 2012)
Fig.1  Incidence of HFMD (cumulative number, as well as severe and fatal cases) in China (Mainland and Taiwan) from 1998 to 2012. Data Source:; (Accessed on July 2, 2012)
VaccineAntigen (adjuvant)DoseAdministration(number of times)Neutralizing antibodytiterProtectiveefficacyAnimal model (age)Reference
Formalin-inactivatedEV71-075 (B4, alum)107 TCID50i.p. (2)76–173ICR mice (3–4 weeks)[62]
EV71-117 (B4, alum)107 TCID5076–173
Heat-inactivatedB4 (FC)10 μgi.p. (3)64BALB/c mice (6 weeks)[22]
VP1 polypeptideSP55 (FC)50 μg8
VP1 polypeptideSP70 (FC)50 μg32
Heat-inactivatedC2 (FC)10 μgi.p. (2)2 04812/19Immunization:ICR female adult miceChallenge:ICR neonatal mice (1 day)[30]
VLP-baculovirusC2 (FC)10 μg8 19216/18
Formalin-inactivatedB3 (alum)20 μgi.p. (2)>512ICR mice (4–6 weeks)[24]
4 μgs.c. (2)0/8ICR mice (14 days)
Live virusStrain 0875 × 106 TCID50i.p. (2)288BALB/c mice (6 weeks)[63]
Strain 085294
Heat-inactivatedStrain 087 (Al(OH)3)448
Strain 085 (Al(OH)3)384
VLP-baculovirusC2 (FC)10 μgi.p. (2)1 448BALB/c mice (6–8 weeks)[31]
B5 (FC)10 μg5 793
Formalin-inactivatedC2 (MP4, alum)20 μgs.c. (3)256100%Vaccination:BALB/c female adult miceChallenge:BALB/c neonatal mice (1 day)[64]
Formalin-inactivatedC4 (Vac-1, alum)3.125 Ui.p. (2)6 (C4)0/11Vaccination:BALB/c female adult miceChallenge:BALB/c neonatal mice (5 days)[54]
12.5 U50 (C4)10/16
50 U200 (C4)16/16
200 U50 (C4)21/21
800 U128 (C4)18/18
C4 (Vac-2, alum)3.125 Ui.p. (2)6023/25Vaccination:BALB/c female adult miceChallenge:BALB/c neonatal mice (5 days)
12.5 U6416/24
50 U19217/17
200 U19221/21
800 U>256 (C4)25/25
Formalin-inactivatedB4, alum (E particle)0.5 μgi.m. (2)188BALB/c mice (6–8 weeks)[26]
2.5 μg906
B4, alum (F particle)0.5 μg1 604
2.5 μg2 020
Formalin-inactivatedB4 (PBS)1 μgi.m. (2)105BALB/c mice (6–8 weeks)[21]
5 μg214
B4 (AlPO4)1 μg322
2 μg416
5 μg624
B4 (Al(OH)3)1 μg47
2 μg62
Formalin-inactivatedC4 (Al(OH)3)100 Ui.m. (1)7.4Infants(Prevaccination antibody titer:<8)[34]
200 U2.5
400 U6.8
100 Ui.m. (2)28.5
200 U39.9
400 U127.3
100 Ui.m. (3)202.7
200 U296.8
400 U639.5
Formalin-inactivatedC4 (Al(OH)3)40 EUs.c. (2)500100%Vaccination:BALB/c female adult miceChallenge:BALB/c neonatal mice(2 days)[20]
160 EU800100%
640 EU850100%
Live virusC4104 CCID50s.c. (2)950
Formalin-inactivatedC4 (Al(OH)3)40 EUs.c. (2)300102 copies/100 mg of tissueRhesus monkeys (2–3.5 years)
160 EU600No virus load in anytissue
640 EU600No virus load in anytissue
Live virusC4105 CCID50s.c. (2)800
Formalin-inactivatedB4 (alum)2 μgi.m. (2)233–443Mice[37]
10 μg654Rats
5 μgi.m. (3)13 575–17 093Rabbits
10 μg13 318–19 308
5 μgi.m. (3)3 169Macaques
10 μg5 623–8 912
VLP-baculovirusC2 (Al(OH)3)20 μgi.m. (3)16 384Macaques[32]
100 μg256
Formalin-inactivatedC2 (neu, Al(OH)3)20 μgi.m. (3)256
Tab.1  Literature published from 2007 to 2012 on EV71 vaccine candidates
No.Research unitsStrain genotypeCell matrixProduction techniqueDevelopment progressClinicalTrials.Gov Identifier
1Beijing Vigoo Biological Co., Ltd.C4VeroBioreactor, inactivationPhase III clinical trialNCT01508247
2Sinovac Biotech Co., Ltd. [34]C4VeroCell factory, inactivationPhase III clinical trialNCT01507857
3Institute of Medical Biology, CAMSC4KMB17Roller bottle, inactivationPhase III clinical trialNCT01569581
4National Health Research Institutes, Taiwan, China [37]B4VeroRoller bottle, inactivationPhase I clinical trialNCT01268787
5Invitrogen Pte. Ltd., Singapore [2]–, inactivationPhase I clinical trialNCT01376479
6Adimmune, Taiwan, China [2]VeroBioreactor, inactivationPreclinical phase
7Beijing Luzhu Biopharmaceutical Co., Ltd., etc.C4Vero–, inactivationPreclinical phase
Tab.2  Progress in the development of inactivated EV71 vaccines
1 Xu J, Qian Y, Wang S, Serrano JM, Li W, Huang Z, Lu S. EV71: an emerging infectious disease vaccine target in the Far East? Vaccine 2010; 28(20):3516–3521 20304038
doi: 10.1016/j.vaccine.2010.03.003
2 Lee MS, Chang LY. Development of enterovirus 71 vaccines. Expert Rev Vaccines 2010; 9(2): 149–156
doi: 10.1586/erv.09.152 pmid:20109026
3 Bible JM, Pantelidis P, Chan PK, Tong CY. Genetic evolution of enterovirus 71: epidemiological and pathological implications. Rev Med Virol 2007; 17(6): 371–379
doi: 10.1002/rmv.538 pmid:17487831
4 Schmidt NJ, Lennette EH, Ho HH. An apparently new enterovirus isolated from patients with disease of the central nervous system. J Infect Dis 1974; 129(3): 304–309
doi: 10.1093/infdis/129.3.304 pmid:4361245
5 McMinn PC, Stratov I, Nagarajan L, Davis S. Neurological manifestations of enterovirus 71 infection in children during a hand, foot and mouth disease outbreak in Western Australia. Clin Infect Dis 2001; 32: 236–242
doi: 10.1086/318454 pmid:11170913
6 Chumakov M, Voroshilova M, Shindarov L, Lavrova I, Gracheva L, Koroleva G, Vasilenko S, Brodvarova I, Nikolova M, Gyurova S, Gacheva M, Mitov G, Ninov N, Tsylka E, Robinson I, Frolova M, Bashkirtsev V, Martiyanova L, Rodin V. Enterovirus 71 isolated from cases of epidemic poliomyelitis-like disease in Bulgaria. Arch Virol 1979; 60(3–4): 329–340
doi: 10.1007/BF01317504 pmid:228639
7 Nagy G, Takátsy S, Kukán E, Mihály I, D?m?k I. Virological diagnosis of enterovirus type 71 infections: experiences gained during an epidemic of acute CNS diseases in Hungary in 1978. Arch Virol 1982; 71(3): 217–227
doi: 10.1007/BF01314873 pmid:6285858
8 Mizuta K, Abiko C, Murata T, Matsuzaki Y, Itagaki T, Sanjoh K, Sakamoto M, Hongo S, Murayama S, Hayasaka K. Frequent importation of enterovirus 71 from surrounding countries into the local community of Yamagata, Japan, between 1998 and 2003. J Clin Microbiol 2005; 43(12): 6171–6175
doi: 10.1128/JCM.43.12.6171-6175.2005 pmid:16333123
9 Ma E, Lam T, Chan KC, Wong C, Chuang SK. Changing epidemiology of hand, foot, and mouth disease in Hong Kong, 2001–2009. Jpn J Infect Dis 2010; 63(6): 422–426
10 Ho M, Chen ER, Hsu KH, Twu SJ, Chen KT, Tsai SF, Wang JR, Shih SR. An epidemic of enterovirus 71 infection in Taiwan. Taiwan Enterovirus Epidemic Working Group . N Engl J Med . 1999; 341(13): 929–935
11 Sarma N, Sarkar A, Mukherjee A, Ghosh A, Dhar S, Malakar R. Epidemic of hand, foot and mouth disease in West Bengal, India in August, 2007: a multicentric study. Indian J Dermatol 2009; 54(1): 26–30
doi: 10.4103/0019-5154.48982 pmid:20049265
12 Kim KH. Enterovirus 71 infection: An experience in Korea, 2009. Korean J Pediatr 2010; 53(5): 616–622
doi: 10.3345/kjp.2010.53.5.616 pmid:21189926
13 Chan LG, Parashar UD, Lye MS, Ong FG, Zaki SR, Alexander JP, Ho KK, Han LL, Pallansch MA, Suleiman AB, Jegathesan M, Anderson LJ; Outbreak Study Group. Deaths of children during an outbreak of hand, foot, and mouth disease in sarawak, malaysia: clinical and pathological characteristics of the disease. Clin Infect Dis 2000; 31(3): 678–683
doi: 10.1086/314032 pmid:11017815
14 Tan X, Huang X, Zhu S, Chen H, Yu Q, Wang H, Huo X, Zhou J, Wu Y, Yan D, Zhang Y, Wang D, Cui A, An H, Xu W. The persistent circulation of enterovirus 71 in People’s Republic of China: causing emerging nationwide epidemics since 2008. PLoS ONE 2011; 6(9): e25662
doi: 10.1371/journal.pone.0025662 pmid:21980521
15 Tu PV, Thao NT, Perera D, Huu TK, Tien NT, Thuong TC, How OM, Cardosa MJ, McMinn PC. Epidemiologic and virologic investigation of hand, foot, and mouth disease, southern Vietnam, 2005. Emerg Infect Dis 2007; 13(11): 1733–1741
doi: 10.3201/eid1311.070632 pmid:18217559
16 Chua KB, Kasri AR. Hand foot and mouth disease due to enterovirus 71 in Malaysia. Virol Sin 2011; 26(4): 221–228
doi: 10.1007/s12250-011-3195-8 pmid:21847753
17 Wang SM, Ho TS, Lin HC, Lei HY, Wang JR, Liu CC. Reemerging of enterovirus 71 in Taiwan: the age impact on disease severity. Eur J Clin Microbiol Infect Dis 2012; 31(6): 1219–1224
doi: 10.1007/s10096-011-1432-6 pmid:21983920
18 AbuBakar S, Sam IC, Yusof J, Lim MK, Misbah S, Hooi PS, MatRahim N. Enterovirus 71 outbreak, Brunei. Emerg Infect Dis 2009; 15(1): 79–82
doi: 10.3201/eid1501.080264 pmid:19116058
19 National notifiable diseases announced by Ministry of Health of the People’s Republic of China. (Accessed on March 22, 2012)
20 Dong C, Liu L, Zhao H, Wang J, Liao Y, Zhang X, Na R, Liang Y, Wang L, Li Q. Immunoprotection elicited by an enterovirus type 71 experimental inactivated vaccine in mice and rhesus monkeys. Vaccine 2011; 29(37): 6269–6275
doi: 10.1016/j.vaccine.2011.06.044 pmid:21722686
21 Chang JY, Chang CP, Tsai HH, Lee CD, Lian WC, Ih Jen Su, Sai IH, Liu CC, Chou AH, Lu YJ, Chen CY, Lee PH, Chiang JR, Chong PC. Selection and characterization of vaccine strain for Enterovirus 71 vaccine development. Vaccine 2012; 30(4): 703–711
doi: 10.1016/j.vaccine.2011.11.087 pmid:22142585
22 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
doi: 10.1016/j.virusres.2006.12.005 pmid:17222936
23 Arita M, Nagata N, Iwata N, Ami Y, Suzaki Y, Mizuta K, Iwasaki T, Sata T, Wakita T, Shimizu H. 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
doi: 10.1128/JVI.02856-06 pmid:17567701
24 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(1): 661–665
doi: 10.1128/JVI.00999-09 pmid:19864378
25 Liu CC, Guo MS, Lin FH, Hsiao KN, Chang KH, Chou AH, Wang YC, Chen YC, Yang CS, Chong PC. Purification and characterization of enterovirus 71 viral particles produced from vero cells grown in a serum-free microcarrier bioreactor system. PLoS ONE 2011; 6(5): e20005
doi: 10.1371/journal.pone.0020005 pmid:21603631
26 Wang X, Peng W, Ren J, Hu Z, Xu J, Lou Z, Li X, Yin W, Shen X, Porta C, Walter TS, Evans G, Axford D, Owen R, Rowlands DJ, Wang J, Stuart DI, Fry EE, Rao Z. A sensor-adaptor mechanism for enterovirus uncoating from structures of EV71. Nat Struct Mol Biol 2012; 19(4): 424–429
doi: 10.1038/nsmb.2255 pmid:22388738
27 Plevka P, Perera R, Cardosa J, Kuhn RJ, Rossmann MG. Crystal structure of human enterovirus 71. Science 2012; 336(6086): 1274
doi: 10.1126/science.1218713 pmid:22383808
28 Chung YC, Huang JH, Lai CW, Sheng HC, Shih SR, Ho MS, Hu YC. Expression, purification and characterization of enterovirus-71 virus-like particles. World J Gastroenterol 2006; 12(6): 921–927
29 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
doi: 10.1186/1479-0556-5-6 pmid:17445254
30 Chung YC, Ho MS, Wu JC, Chen WJ, Huang JH, Chou ST, Hu YC. Immunization with virus-like particles of enterovirus 71 elicits potent immune responses and protects mice against lethal challenge. Vaccine 2008; 26(15): 1855–1862
doi: 10.1016/j.vaccine.2008.01.058 pmid:18329759
31 Chung CY, Chen CY, Lin SY, Chung YC, Chiu HY, Chi WK, Lin YL, Chiang BL, Chen WJ, Hu YC. Enterovirus 71 virus-like particle vaccine: improved production conditions for enhanced yield. Vaccine 2010; 28(43): 6951–6957
doi: 10.1016/j.vaccine.2010.08.052 pmid:20797455
32 Lin YL, Yu CI, Hu YC, Tsai TJ, Kuo YC, Chi WK, Lin AN, Chiang BL. Enterovirus type 71 neutralizing antibodies in the serum of macaque monkeys immunized with EV71 virus-like particles. Vaccine 2012; 30(7): 1305–1312
doi: 10.1016/j.vaccine.2011.12.081 pmid:22214888
33 Arita M, Shimizu H, Nagata N, Ami Y, Suzaki Y, Sata T, Iwasaki T, Miyamura T. Temperature-sensitive mutants of enterovirus 71 show attenuation in cynomolgus monkeys. J Gen Virol 2005; 86(Pt 5): 1391–1401
doi: 10.1099/vir.0.80784-0 pmid:15831951
34 Li YP, Liang ZL, Gao Q, Huang LR, Mao QY, Wen SQ, Liu Y, Yin WD, Li RC, Wang JZ. Safety and immunogenicity of a novel human Enterovirus 71 (EV71) vaccine: a randomized, placebo-controlled, double-blind, Phase I clinical trial. Vaccine 2012; 30(22): 3295–3303
doi: 10.1016/j.vaccine.2012.03.010 pmid:22426327
35 Meng FY, Li JX, Li XL, Chu K, Zhang YT, Ji H, Li L, Liang ZL, Zhu FC. Tolerability and immunogenicity of an inactivated enterovirus 71 vaccine in Chinese healthy adults and children: an open label, phase 1 clinical trial. Hum Vaccin Immunother 2012; 8(5): 668–674
doi: 10.4161/hv.19521 pmid:22634437
36 Wu SC, Liu CC, Lian WC. Optimization of microcarrier cell culture process for the inactivated enterovirus type 71 vaccine development. Vaccine 2004; 22(29–30): 3858–3864
doi: 10.1016/j.vaccine.2004.05.037 pmid:15364432
37 Chou AH, Liu CC, Chang CP, Guo MS, Hsieh SY, Yang WH, Chao HJ, Wu CL, Huang JL, Lee MS, Hu AY, Lin SC, Huang YY, Hu MH, Chow YH, Chiang JR, Chang JY, Chong P. Pilot scale production of highly efficacious and stable enterovirus 71 vaccine candidates. PLoS ONE 2012; 7(4): e34834
doi: 10.1371/journal.pone.0034834 pmid:22529942
38 Inviragen Hand, Foot And Mouth Disease Vaccine Generates Immune Responses In 100% of Study Participants . (Accessed on June 22, 2012)
39 Mao Q, Li N, Yu X, Yao X, Li F, Lu F, Zhuang H, Liang Z, Wang J. Antigenicity, animal protective effect and genetic characteristics of candidate vaccine strains of enterovirus 71. Arch Virol 2012; 157(1): 37–41
doi: 10.1007/s00705-011-1136-3 pmid:21984267
40 Liang Z, Mao Q, Gao Q, Li X, Dong C, Yu X, Yao X, Li F, Yin W, Li Q, Shen X, Wang J. Establishing China’s national standards of antigen content and neutralizing antibody responses for evaluation of enterovirus 71 (EV71) vaccines. Vaccine 2011; 29(52): 9668–9674
doi: 10.1016/j.vaccine.2011.10.018 pmid:22015395
41 Mao QY, He P, Yu X, Li N, Hao CS, Gao Q, Dong CH, Liang ZL, Li FX, Shen XL, Wang JZ. Laboratory Evaluation of Method for Determination of Neutralizing Antibody against Human Enterovirus 71. Chin J Biologicals (Zhongguo Sheng Wu Zhi Pin Xue Za Zhi) 2010; 23(8): 885–888 (in Chinese)
42 Liu CC, Chang HW, Yang G, Chiang JR, Chow YH, Sai IH, Chang JY, Lin SC, Sia C, Hsiao CH, Chou AH, Chong P. Development of a quantitative enzyme linked immunosorbent assay for monitoring the Enterovirus 71 vaccine manufacturing process. J Virol Methods 2011; 176(1–2): 60–68
doi: 10.1016/j.jviromet.2011.06.001 pmid:21704080
43 Jia H, Cai F, Gao Q, Zhang JS, Jing SR. Development of A Quantitative ELISA Method for EV71 Antigen. Chin J Biologicals (Zhongguo Sheng Wu Zhi Pin Xue Za Zhi) 2010; 23(1): 87–90 (in Chinese)
44 Long RX, Xie ZP, Yang R, Li H, Bai HZ, Dong CH, Liu LD, Li QH. Development and Application of BA-ELISA Method for EV71 Antigen. Chin J Biologicals (Zhongguo Sheng Wu Zhi Pin Xue Za Zhi) 2009; 22: 1230–1232 (in Chinese)
45 Yu CK, Chen CC, Chen CL, Wang JR, Liu CC, Yan JJ, Su IJ. Neutralizing antibody provided protection against enterovirus type 71 lethal challenge in neonatal mice. J Biomed Sci 2000; 7(6): 523–528
doi: 10.1007/BF02253368 pmid:11060501
46 Chen YC, Yu CK, Wang YF, Liu CC, Su IJ, Lei HY. A murine oral enterovirus 71 infection model with central nervous system involvement. J Gen Virol 2004; 85(Pt 1): 69–77
doi: 10.1099/vir.0.19423-0 pmid:14718621
47 Wang YF, Chou CT, Lei HY, Liu CC, Wang SM, Yan JJ, Su IJ, Wang JR, Yeh TM, Chen SH, Yu CK. A mouse-adapted enterovirus 71 strain causes neurological disease in mice after oral infection. J Virol 2004; 78(15): 7916–7924
doi: 10.1128/JVI.78.15.7916-7924.2004 pmid:15254164
48 Liu ML, Lee YP, Wang YF, Lei HY, Liu CC, Wang SM, Su IJ, Wang JR, Yeh TM, Chen SH, Yu CK. Type I interferons protect mice against enterovirus 71 infection. J Gen Virol 2005; 86(Pt 12): 3263–3269
doi: 10.1099/vir.0.81195-0 pmid:16298971
49 Ong KC, Badmanathan M, Devi S, Leong KL, Cardosa MJ, Wong KT. Pathologic characterization of a murine model of human enterovirus 71 encephalomyelitis. J Neuropathol Exp Neurol 2008; 67(6): 532–542
doi: 10.1097/NEN.0b013e31817713e7 pmid:18520772
50 Nishimura Y, Shimojima M, Tano Y, Miyamura T, Wakita T, Shimizu H. Human P-selectin glycoprotein ligand-1 is a functional receptor for enterovirus 71. Nat Med 2009; 15(7): 794–797
doi: 10.1038/nm.1961 pmid:19543284
51 Yamayoshi S, Yamashita Y, Li J, Hanagata N, Minowa T, Takemura T, Koike S. Scavenger receptor B2 is a cellular receptor for enterovirus 71. Nat Med 2009; 15(7): 798–801
doi: 10.1038/nm.1992 pmid:19543282
52 Liu J, Dong W, Quan X, Ma C, Qin C, Zhang L. Transgenic expression of human P-selectin glycoprotein ligand-1 is not sufficient for enterovirus 71 infection in mice. Arch Virol 2012; 157(3): 539–543
doi: 10.1007/s00705-011-1198-2 pmid:22187102
53 Khong WX, Yan B, Yeo H, Tan EL, Lee JJ, Ng JK, Chow VT, Alonso S. A non-mouse-adapted enterovirus 71 (EV71) strain exhibits neurotropism, causing neurological manifestations in a novel mouse model of EV71 infection. J Virol 2012; 86(4): 2121–2131
doi: 10.1128/JVI.06103-11 pmid:22130542
54 Bek EJ, Hussain KM, Phuektes P, Kok CC, Gao Q, Cai F, Gao Z, McMinn PC. Formalin-inactivated vaccine provokes cross-protective immunity in a mouse model of human enterovirus 71 infection. Vaccine 2011; 29(29–30): 4829–4838
doi: 10.1016/j.vaccine.2011.04.070 pmid:21550375
55 Nagata N, Shimizu H, Ami Y, Tano Y, Harashima A, Suzaki Y, Sato Y, Miyamura T, Sata T, Iwasaki T. Pyramidal and extrapyramidal involvement in experimental infection of cynomolgus monkeys with enterovirus 71. J Med Virol 2002; 67(2): 207–216
doi: 10.1002/jmv.2209 pmid:11992581
56 Liu L, Zhao H, Zhang Y, Wang J, Che Y, Dong C, Zhang X, Na R, Shi H, Jiang L, Wang L, Xie Z, Cui P, Xiong X, Liao Y, Zhao S, Gao J, Tang D, Li Q. Neonatal rhesus monkey is a potential animal model for studying pathogenesis of EV71 infection. Virology 2011; 412(1): 91–100
doi: 10.1016/j.virol.2010.12.058 pmid:21262515
57 Chang LY, King CC, Hsu KH, Ning HC, Tsao KC, Li CC, Huang YC, Shih SR, Chiou ST, Chen PY, Chang HJ, Lin TY. 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
doi: 10.1542/peds.109.6.e88 pmid:12042582
58 Ooi EE, Phoon MC, Ishak B, Chan SH. Seroepidemiology of human enterovirus 71, Singapore. Emerg Infect Dis 2002; 8(9): 995–997
doi: 10.3201/eid0809.010397 pmid:12194783
59 Luo ST, Chiang PS, Chao AS, Liou GY, Lin R, Lin TY, Lee MS. Enterovirus 71 maternal antibodies in infants, Taiwan. Emerg Infect Dis 2009; 15(4): 581–584
60 Mao QY, Liao XY, Yu X, Li N, Zhu FC, Zeng Y, Liang ZL, Li FX, Wang JZ, Lu FM, Zhuang H. Dynamic change of mother-source neutralizing antibodies against enterovirus 71 and coxsackievirus A16 in infants. Chin Med J (Engl) 2010; 123(13): 1679–1684
61 Mao QY, Yang ZW, Yu X, Jing P, He P, Huang WJ, Wu XY, Wan ZJ, Liang ZL, Li FX, Wang JZ. Epidemic Tendency of Neutralizing Antibody against Enterovirus 71 and Coxsackievirus A 16 in Infants in Rural Area of Kaifeng City, Henan Province, China. Chin J Biologicals (Zhongguo Sheng Wu Zhi Pin Xue Za Zhi) 2009; 22(9): 911–913 (in Chinese)
62 Liu CC, Lian WC, Butler M, Wu SC. High immunogenic enterovirus 71 strain and its production using serum-free microcarrier Vero cell culture. Vaccine 2007; 25(1): 19–24
doi: 10.1016/j.vaccine.2006.06.083 pmid:16919374
63 Li XL, Zhang ZY, Wang XX, Yang YJ, Hao CS, Zhao M, He WW, Zhang C, Shen XL. Identification and immunogenidty of enterovirus 71 isolates. Chin J Microbiol Immunol (Zhonghua Wei Sheng Wu Xue He Mian Yi Xue Za Zhi) 2009; 29(10): 944–948 (in Chinese)
64 Chen CW, Lee YP, Wang YF, Yu CK. Formaldehyde-inactivated human enterovirus 71 vaccine is compatible for co-immunization with a commercial pentavalent vaccine. Vaccine 2011; 29(15): 2772–2776
doi: 10.1016/j.vaccine.2011.01.094 pmid:21315698
Related articles from Frontiers Journals
[1] Qian Wang, Linqi Zhang. Broadly neutralizing antibodies and vaccine design against HIV-1 infection[J]. Front. Med., 2020, 14(1): 30-42.
[2] Xiaoxin Wu, Lanlan Xiao, Lanjuan Li. Research progress on human infection with avian influenza H7N9[J]. Front. Med., 2020, 14(1): 8-20.
[3] Daniel Stadlbauer, Raffael Nachbagauer, Philip Meade, Florian Krammer. Universal influenza virus vaccines: what can we learn from the human immune response following exposure to H7 subtype viruses?[J]. Front. Med., 2017, 11(4): 471-479.
[4] Ali A. Rabaan, Ali M. Bazzi, Shamsah H. Al-Ahmed, Jaffar A. Al-Tawfiq. Molecular aspects of MERS-CoV[J]. Front. Med., 2017, 11(3): 365-377.
[5] Zeyu Chen,Rong Guo,Jianghong Xu,Chuangjun Qiu. Immunogenicity and protective immunity against otitis media caused by pneumococcus in mice of Hib conjugate vaccine with PsaA protein carrier[J]. Front. Med., 2016, 10(4): 490-498.
[6] Yumei Wen, Xuanyi Wang, Bin Wang, Zhenhong Yuan. Vaccine therapies for chronic hepatitis B: can we go further?[J]. Front Med, 2014, 8(1): 17-23.
[7] HE Yu, YANG Shuhua, LIU Yong, LI Tao. Antitumor immunity of human SART3 gene vaccine against mouse tumor [J]. Front. Med., 2008, 2(1): 51-57.
[8] XU Qingwen, CHEN Weifeng. Developing effective tumor vaccines: basis, challenges and perspectives[J]. Front. Med., 2007, 1(1): 11-19.
Full text