Combined peptides of human enterovirus 71 protect against virus infection in mice.

Human enterovirus 71 (EV71) is a cause of hand, foot and mouth disease (HMFD) in children under 6 years old, and could cause serious neurological complications in some patients. Numerous large outbreaks of EV71 caused HMFD have occurred recently in Asia, especially in China. The cross-reactivity of EV71 with human brain tissue was observed and the cross-reactivity inducing regions were identified in previously study, which suggested that there were two regions in structural proteins of virus should be avoided in the vaccine. Six peptides without cross-reactivity were selected and combined into three vaccine candidates and applied in further evaluation in neonatal mice. The Vac6 comprising the peptides of P(70-159), P(140-249), P(324-443) and P(746-876) of the structural proteins could provide effective protection on pups against virus infection, as shown in viral copies detection and histopathology examination. Immunohistochemical staining results indicated that Vac6 had no cross-reactivity with human brain tissues. Our results suggested that Vac6 could have potential clinical value against EV71 epidemics caused mainly by C4 strains in the mainland of China.

The cross-reactivity of the enterovirus 71 to human brain tissue and identification of the cross-reactivity related fragments.

BACKGROUND: EV71 occasionally cause a series of severe neurological symptoms, including aseptic meningitis, encephalitis, and poliomyelitis-like paralysis. However, the neurological destruction mechanism was remained to be clarified. This study described the cross reaction between EV71 induced IgG and human brain tissue. RESULTS: Cross reaction of the IgG from 30 EV71 infected patients' sera to human tissues of cerebra was observed, which suggested that some EV71 antigens could induce IgG cross-reactivity to human cerebra. To identify the regions of EV71 virus that containing above antigens, the polypeptide of virus was divided into 19 peptides by expression in prokaryotes cell. Mouse anti-sera of these peptides was prepared and applied in immunohistochemical staining with human adult and fetus brain tissue, respectively. The result indicated the 19 peptides can be classified into three groups: strong cross-reactivity, weak cross-reactivity and no cross-reactivity with human brain tissue according the cross reaction activity. Then, the increased Blood Brain Barrier (BBB) permeability and permits IgG entry in neonatal mice after EV71 infection was determined. CONCLUSION: EV71 induced IgG could enter BBB and cross-reacted with brain tissue in EV71 infected neonatal mice, and then the peptides of EV71 that could induce cross-reactivity with brain tissue were identified, which should be avoided in future vaccine designing.