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Open Access Research

Recombinant tandem multi-linear neutralizing epitopes of human enterovirus 71 elicited protective immunity in mice

Yue-Xiang Li12, Hui Zhao2, Rui-Yuan Cao2, Yong-Qiang Deng2, Jian-Feng Han2, Shun-Ya Zhu2, Jie Ma2, Long Liu12, E-De Qin12 and Cheng-Feng Qin12*

  • * Corresponding author: Cheng-Feng Qin qincf@bmi.ac.cn

  • † Equal contributors

Author Affiliations

1 Graduate School, Anhui Medical University, Hefei 230032, Anhui, China

2 Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China

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Virology Journal 2014, 11:79  doi:10.1186/1743-422X-11-79

Published: 6 May 2014

Abstract

Background

Human Enterovirus 71 (EV71) has emerged as the leading cause of viral encephalitis in children, especially in the Asia-Pacific regions. EV71 vaccine development is of high priority at present, and neutralization antibodies have been documented to play critical roles during in vitro and in vivo protection against EV71 infection.

Results

In this study, a novel strategy to produce EV71 vaccine candidate based on recombinant multiple tandem linear neutralizing epitopes (mTLNE) was proposed. The three well identified EV71 linear neutralizing epitopes in capsid proteins, VP1-SP55, VP1-SP70 and VP2-SP28, were sequentially linked by a Gly-Ser linker ((G4S)3), and expressed in E.coli in fusion with the Trx and His tag at either terminal. The recombinant protein mTLNE was soluble and could be purified by standard affinity chromatography. Following three dosage of immunization in adult mice, EV71-specific IgG and neutralization antibodies were readily induced by recombinant mTLNE. IgG subtyping demonstrated that lgG1 antibodies dominated the mTLNE-induced humoral immune response. Especially, cytokine profiling in spleen cells from the mTLNE-immunized mice revealed high production of IL-4 and IL-6. Finally, in vivo challenge experiments showed that passive transfer with anti-mTLNE sera conferred full protection against lethal EV71 challenge in neonatal mice.

Conclusion

Our results demonstrated that this rational designed recombinant mTLNE might have the potential to be further developed as an EV71 vaccine in the future.

Keywords:
Enterovirus 71; Vaccine; Linear neutralizing epitopes