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Preliminary Study on Antibody Response to Enterovirus71

Author: PanQingSong
Tutor: ZhangHongFeng; LengQiBin
School: East China Normal University
Course: Biomedical
Keywords: Enterovirus71 Poliovirus Cross-reactive antibody linearneutralizating epitope
CLC: R392
Type: Master's thesis
Year: 2012
Downloads: 50
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Abstract

In recent years, Hand-foot-mouth disease (HFMD) tends to be a durative epidemic in china, with fatal cases increasing annually. Many enteroviruses can cause HFMD, mostly affecting infants and younger children. Although the disease is generally self-limited, HFMD caused by EV71infection sometimes develops into severe complications, such as aseptic meningitis, brain stem encephalitis, poliomyelitis-like paralysis and pulmonary edema, of which pulmonary edema is the severest complication and the main fatal inducer. Currently, molecular mechanisms of pathogenesis underlying EV71infection are unclear. Moreover, no specific medicines and vaccines are available for the moment. In this study, some preliminary investigations of humoral response to EV71are made to be expected to shed some light on pathogenesis, treatment of EV71infection and vaccine development. The contents of this research include:(1) to investigate the cross-reactivity between the antibodies against enterovirus71(EV71) and Poliovirus (PV) by clinical serum samples’detection and further validation of animal experiment;(2) to investigate whether neutralization epitopes SP70and SP55can elicit corresponding antibodies in EV71-infected patients.We use enzyme-linked immunosorbent assay (ELISA) to detect the reactivity of sera of never-EV71-infected children to EV71or PV. The results indicates PV-positive serum has a high IgG seroprevalence for EV71(77.8%), and relative content of EV71-directed and PV-directed IgG antibodies in these sera correlates well (r=0.58). Further neutralization test indicates PV-positive children’s sera cannot neutralize EV71even in a dilution of1:4. After co-incubation with PV-positive but EV71-negative children’s sera, EV71infected THP-1cells.24hours post-infection, EV71entering THP-1was detected by Real-time PCR, and the results indicate at a dilution of1:104, PV-positive serum can significantly enhance entry of EV71into THP-1(p<0.01). All of the above indicate PV vaccination can elicit antibodies cross-reacting to EV71. Although these antibodies are non-neutralizing antibodies, these non-neutralizing antibodies can enhance entry of EV71into THP-1, implying that non-neutralizing antibodies may correlate with pathogenesis of EV71infection.Previous researchers obtained two linear neutralization epitopes of EV71, i.e. SP70and SP55, which can elicit corresponding neutralization antibodies in mice. To investigate the reactivity of these two epitopes in human, we synthesized SP70and SP55and collected sera from EV71-infected convalescent children or never EV71-infected children, and then reactivity of SP70or SP55to the two kinds of sera is investigated by ELISA. The results show there are no differences between reactivity of SP70or SP55to EV71-infected children’s serum and to never-EV71-infected children’s serum. EV71-infected children’s sera were tested for their neutralizing titers after co-incubation with SP70or SP55in advance and we found that presence of SP70or SP55did not result in decreases in neutralizing titers. In conclusion, the research above probably indicate SP70and SP55are not immuno-dominant B cell epitopes and thus cannot elicit corresponding neutalizating antibodies in human, which implies that SP70or SP55should not be used in the development of vaccines against EV71, especially peptide vaccine.

Preliminary Study on Antibody Response to Enterovirus71

Abstract

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