Abstract
BackgroundHuman 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.ResultsIn 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.ConclusionOur results demonstrated that this rational designed recombinant mTLNE might have the potential to be further developed as an EV71 vaccine in the future.
Highlights
Human enterovirus 71 (EV71), a typical single-stranded, positive-sense RNA virus, belongs to the Enterovirus genus of the Picornaviridae family
Our results demonstrated that this rational designed recombinant multiple tandem linear neutralizing epitopes (mTLNE) might have the potential to be further developed as an Enterovirus 71 (EV71) vaccine in the future
After a single purification with Ni-NTA agarose, recombinant mTLNE was isolated as a single band
Summary
Human enterovirus 71 (EV71), a typical single-stranded, positive-sense RNA virus, belongs to the Enterovirus genus of the Picornaviridae family. EV71 has emerged as the most important causative agent of Hand, Foot and Mouse disease (HFMD) affecting mostly young children, especially those younger than 5 years old. The clinical symptoms of EV71 infection include simple exanthema, serious aseptic meningitis, acute flaccid paralysis as well as brainstem encephalitis [1]. Present in most countries, the largest outbreaks of disease have been seen in the Asia-Pacific region over the past 15 years [2,3,4,5,6], Vaccination probably offers the best option for disease control, but there is no available licensed vaccine against EV71. 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
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