title: Neutralizing antibodies induced by recombinant virus-like particles of enterovirus 71 genotype C4 inhibit infection at pre- and post-attachment steps.
abstract: BACKGROUND
  Enterovirus 71 (EV71) is a major causative agent of hand, foot and mouth disease, which has been prevalent in Asia-Pacific regions, causing significant morbidity and mortality in young children. Antibodies elicited by experimental EV71 vaccines could neutralize infection in vitro and passively protect animal models from lethal challenge, indicating that neutralizing antibodies play an essential role in protection. However, how neutralizing antibodies inhibit infection in vitro remains unclear.
  
  
  RESULTS
  In the present study, we explored the mechanisms of neutralization by antibodies against EV71 virus-like particles (VLPs). Recombinant VLPs of EV71 genotype C4 were produced in insect cells using baculovirus vectors. Immunization with the VLPs elicited a high-titer, EV71-specific antibody response in mice. Anti-VLP mouse sera potently neutralized EV71 infection in vitro. The neutralizing antibodies in the anti-VLP mouse sera were found to target mainly an extremely conserved epitope (FGEHKQEKDLEYGAC) located at the GH loop of the VP1 protein. The neutralizing anti-VLP antisera were able to inhibit virus binding to target cells efficiently. In addition, post-attachment treatment of virus-bound cells with the anti-VLP antisera also neutralized virus infection, although the antibody concentration required was higher than that of the pre-attachment treatment.
  
  
  CONCLUSIONS
  Collectively, our findings represent a valuable addition to the understanding of mechanisms of EV71 neutralization and have strong implications for EV71 vaccine development.
authors: Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors: Zhiqiang
authors: Z
authors: Ku
authors: Xiaohua
authors: X
authors: Ye
authors: Xulin
authors: X
authors: Huang
authors: Yicun
authors: Y
authors: Cai
authors: Qingwei
authors: Q
authors: Liu
authors: Yan
authors: Y
authors: Li
authors: Zhiguo
authors: Z
authors: Su
authors: Zhong
authors: Z
authors: Huang
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D000917:Antibody Formation; D016367:Baculoviridae / Q000276:immunology; D002522:Chlorocebus aethiops / Q000276:immunology; D029821:Enterovirus A, Human / Q000276:immunology*; D004769:Enterovirus Infections / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005260:Female; D005838:Genotype; D007313:Insecta / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests / Q000379:methods; D061987:Sf9 Cells; D014611:Vaccination / Q000379:methods; D014709:Vero Cells; D014765:Viral Vaccines / Q000276:immunology*; D014771:Virion / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000939:Epitopes; D014765:Viral Vaccines