期刊论文详细信息
BMC Microbiology
Immunization of N terminus of enterovirus 71 VP4 elicits cross-protective antibody responses
Yi Zeng2  Wang Sheng2  Xin Sun5  Paul KS Chan3  Shan Cen1  Yuming Huang4  Xiangqian Xiao2  Wei Liu2  Yu Bai2  Miao Zhao2 
[1] Department of Virology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Science, Beijing PR China;College of Life Science and Bioengineering, Beijing University of Technology, 100, Pingleyuan, Chaoyang District, Beijing 100124, PR China;Department of Microbiology, Chinese University of Hong Kong, Hong Kong PR China;Department of Neurology, Beijing Ditan Hospital, Capital Medical University, Beijing PR China;Research Center for Life Science, Beihua University, 3999, Binjiangdong Road, Jinlin, Jilin Province 132013, PR China
关键词: Chimeric virus-like particle;    Peptide;    VP4;    Vaccine;    Enterovirus 71;   
Others  :  1142411
DOI  :  10.1186/1471-2180-13-287
 received in 2013-09-20, accepted in 2013-12-02,  发布年份 2013
PDF
【 摘 要 】

Background

Enterovirus 71 (EV71) is major cause of hand, foot and mouth disease. Large epidemics of EV71 infection have been recently reported in the Asian-Pacific region. Currently, no vaccine is available to prevent EV71 infection.

Results

The peptide (VP4N20) consisting of the first 20 amino acids at the N-terminal of VP4 of EV71 genotype C4 were fused to hepatitis B core (HBcAg) protein. Expression of fusion proteins in E. coli resulted in the formation of chimeric virus-like particles (VLPs). Mice immunized with the chimeric VLPs elicited anti-VP4N20 antibody response. In vitro microneutralization experiments showed that anti-chimeric VLPs sera were able to neutralize not only EV71 of genotype C4 but also EV71 of genotype A. Neonatal mice model confirmed the neutralizing ability of anti-chimeric VLPs sera. Eiptope mapping led to the identification of a “core sequence” responsible for antibody recognition within the peptide.

Conclusions

Immunization of chimeric VLPs is able to elicit antibodies displaying a broad neutralizing activity against different genotypes of EV71 in vitro. The “core sequence” of EV71-VP4 is highly conserved across EV71 genotypes. The chimeric VLPs have a great potential to be a novel vaccine candidate with a broad cross-protection against different EV71 genotypes.

【 授权许可】

   
2013 Zhao et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20150328051140886.pdf 1938KB PDF download
Figure 8. 75KB Image download
Figure 7. 71KB Image download
Figure 6. 59KB Image download
Figure 5. 71KB Image download
Figure 4. 69KB Image download
Figure 3. 79KB Image download
Figure 2. 37KB Image download
Figure 1. 56KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

Figure 7.

Figure 8.

【 参考文献 】
  • [1]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.
  • [2]Brown BA, Pallansch MA: Complete nucleotide sequence of enterovirus 71 is distinct from poliovirus. Virus Res 1995, 39(2–3):195-205.
  • [3]Chung Y-C, Ho M-S, Wu J-C, Chen W-J, Huang J-H, Chou S-T, Hu Y-C: Immunization with virus-like particles of enterovirus 71 elicits potent immune responses and protects mice against lethal challenge. Vaccine 2008, 26(15):1855-1862.
  • [4]Tuthill T, Groppelli E, Hogle J, Rowlands D: Picornaviruses. In Cell Entry by Non-Enveloped Viruses. 343rd edition. Edited by Johnson JE. Germany: Springer Berlin Heidelberg; 2010:43-89.
  • [5]Chow M, Newman JFE, Filman D, Hogle JM, Rowlands DJ, Brown F: Myristylation of picornavirus capsid protein VP4 and its structural significance. Nature 1987, 327(6122):482-486.
  • [6]Lewis JK, Bothner B, Smith TJ, Siuzdak G: Antiviral agent blocks breathing of the common cold virus. Proc Natl Acad Sci 1998, 95(12):6774-6778.
  • [7]Wang X, Peng W, Ren J, Hu Z, Xu J, Lou Z, Li X, Yin W, Shen X, Porta C, et al.: A sensor-adaptor mechanism for enterovirus uncoating from structures of EV71. Nat Struct Mol Biol 2012, 19(4):424-429.
  • [8]McMinn PC: An overview of the evolution of enterovirus 71 and its clinical and public health significance. FEMS Microbiol Rev 2002, 26(1):91-107.
  • [9]Suzuki Y, Taya K, Nakashima K, Ohyama T, Kobayashi JM, Ohkusa Y, Okabe N: Risk factors for severe hand foot and mouth disease. Pediatr Int 2010, 52(2):203-207.
  • [10]Guan D, van der Sanden S, Zeng H, Li W, Zheng H, Ma C, Su J, Liu Z, Guo X, Zhang X, et al.: Population Dynamics and Genetic Diversity of C4 Strains of Human Enterovirus 71 in Mainland China, 1998–2010. PLoS ONE 2012, 7(9):e44386.
  • [11]Wu Y, Yeo A, Phoon MC, Tan EL, Poh CL, Quak SH, Chow VTK: The largest outbreak of hand; foot and mouth disease in Singapore in 2008: The role of enterovirus 71 and coxsackievirus A strains. Int J Infect Dis 2010, 14(12):e1076-e1081.
  • [12]Iwai M, Masaki A, Hasegawa S, Obara M, Horimoto E, Nakamura K, Tanaka Y, Endo K, Tanaka K, Ueda J, et al.: Genetic changes of coxsackievirus A16 and enterovirus 71 isolated from hand, foot, and mouth disease patients in Toyama, Japan between 1981 and 2007. Japanese journal of infectious diseases 2009, 62(4):254-259.
  • [13]Chen S-C, Chang H-L, Yan T-R, Cheng Y-T, Chen K-T: An Eight-Year Study of Epidemiologic Features of Enterovirus 71 Infection In Taiwan. AmJTrop Med Hyg 2007, 77(1):188-191.
  • [14]Chen K-T, Chang H-L, Wang S-T, Cheng Y-T, Yang J-Y: Epidemiologic Features of Hand-Foot-Mouth Disease and Herpangina Caused by Enterovirus 71 in Taiwan, 1998–2005. Pediatrics 2007, 120(2):e244-e252.
  • [15]Solomon T, Lewthwaite P, Perera D, Cardosa MJ, McMinn P, Ooi MH: Virology, epidemiology, pathogenesis, and control of enterovirus 71. Lancet Infect Dis 2010, 10(11):778-790.
  • [16]Liu C-C, Chou A-H, Lien S-P, Lin H-Y, Liu S-J, Chang J-Y, Guo M-S, Chow Y-H, Yang W-S, Chang KH-W, et al.: Identification and characterization of a cross-neutralization epitope of Enterovirus 71. Vaccine 2011, 29(26):4362-4372.
  • [17]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. Virology journal 2010, 7:106. BioMed Central Full Text
  • [18]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.
  • [19]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 and infection/Institut Pasteur 2007, 9(11):1299-1306.
  • [20]Liu JN, Wang W, Duo JY, Hao Y, Ma CM, Li WB, Lin SZ, Gao XZ, Liu XL, Xu YF, et al.: Combined peptides of human enterovirus 71 protect against virus infection in mice. Vaccine 2010, 28(46):7444-7451.
  • [21]Yoke-Fun C, AbuBakar S: Phylogenetic evidence for inter-typic recombination in the emergence of human enterovirus 71 subgenotypes. BMC microbiology 2006, 6:74. BioMed Central Full Text
  • [22]Huang SW, Kiang D, Smith DJ, Wang JR: Evolution of re-emergent virus and its impact on enterovirus 71 epidemics. Experimental biology and medicine (Maywood, NJ) 2011, 236(8):899-908.
  • [23]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. The New England journal of medicine 1999, 341(13):929-935.
  • [24]Zhang Y, Zhu Z, Yang W, Ren J, Tan X, Wang Y, Mao N, Xu S, Zhu S, Cui A, et al.: An emerging recombinant human enterovirus 71 responsible for the 2008 outbreak of hand foot and mouth disease in Fuyang city of China. Virology journal 2010, 7:94. BioMed Central Full Text
  • [25]Zhang Y, Tan X, Cui A, Mao N, Xu S, Zhu Z, Zhou J, Shi J, Zhao Y, Wang X, et al.: Complete genome analysis of the C4 subgenotype strains of enterovirus 71: predominant recombination C4 viruses persistently circulating in China for 14 years. PLoS One 2013, 8(2):e56341.
  • [26]Wu CN, Lin YC, Fann C, Liao NS, Shih SR, Ho MS: Protection against lethal enterovirus 71 infection in newborn mice by passive immunization with subunit VP1 vaccines and inactivated virus. Vaccine 2001, 20(5–6):895-904.
  • [27]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.
  • [28]Tung WS, Bakar SA, Sekawi Z, Rosli R: DNA vaccine constructs against enterovirus 71 elicit immune response in mice. Genetic vaccines and therapy 2007, 5:6. BioMed Central Full Text
  • [29]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 and infection/Institut Pasteur 2006, 8(7):1671-1678.
  • [30]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. Journal of virology 2007, 81(17):9386-9395.
  • [31]Dong C, Wang J, Liu L, Zhao H, Shi H, Zhang Y, Jiang L, Li Q: Optimized development of a candidate strain of inactivated EV71 vaccine and analysis of its immunogenicity in rhesus monkeys. Human vaccines 2010, 6(12):1028-1037.
  • [32]Liu L, Zhang Y, Wang J, Zhao H, Jiang L, Che Y, Shi H, Li R, Mo Z, Huang T, et al.: Study of the integrated immune response induced by an inactivated EV71 vaccine. PLoS One 2013, 8(1):e54451.
  • [33]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.
  • [34]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.
  • [35]Brown BA, Oberste MS, Alexander JP Jr, Kennett ML, Pallansch MA: Molecular epidemiology and evolution of enterovirus 71 strains isolated from 1970 to 1998. Journal of virology 1999, 73(12):9969-9975.
  • [36]Roivainen M, Piirainen L, Ryä T, Närvänen A, Hovi T: An Immunodominant N-Terminal Region of VP1 Protein of Poliovirion That Is Buried in Crystal Structure Can Be Exposed in Solution. Virology 1993, 195(2):762-765.
  • [37]Li Q, Yafal AG, Lee YM, Hogle J, Chow M: Poliovirus neutralization by antibodies to internal epitopes of VP4 and VP1 results from reversible exposure of these sequences at physiological temperature. J Virol 1994, 68(6):3965-3970.
  • [38]Katpally U, Fu TM, Freed DC, Casimiro DR, Smith TJ: Antibodies to the buried N terminus of rhinovirus VP4 exhibit cross-serotypic neutralization. Journal of virology 2009, 83(14):7040-7048.
  • [39]Hogle J, Chow M, Filman D: Three-dimensional structure of poliovirus at 2.9 A resolution. Science 1985, 229(4720):1358-1365.
  • [40]Fricks CE, Hogle JM: Cell-induced conformational change in poliovirus: externalization of the amino terminus of VP1 is responsible for liposome binding. J Virol 1990, 64(5):1934-1945.
  • [41]Greve JM, Forte CP, Marlor CW, Meyer AM, Hoover-Litty H, Wunderlich D, McClelland A: Mechanisms of receptor-mediated rhinovirus neutralization defined by two soluble forms of ICAM-1. J Virol 1991, 65(11):6015-6023.
  • [42]Davis MP, Bottley G, Beales LP, Killington RA, Rowlands DJ, Tuthill TJ: Recombinant VP4 of human rhinovirus induces permeability in model membranes. Journal of virology 2008, 82(8):4169-4174.
  文献评价指标  
  下载次数:32次 浏览次数:11次