title: Antigenic analysis of divergent genotypes human Enterovirus 71 viruses by a panel of neutralizing monoclonal antibodies: current genotyping of EV71 does not reflect their antigenicity.
abstract: In recent year, Enterovirus 71 (EV71)-associated hand, foot and mouth disease (HFMD) has become an important public health issue in China. EV71 has been classified into genotypes A, B1-B5 and C1-C5. With such genetic diversity, whether the convalescent or recovery antibody responses can cross-protect infections from other genotypes remains a question. Understanding of the antigenicity of such diverse genetic EV71 isolates is crucial for the EV71 vaccine development. Here, a total of 186 clones anti-EV71 MAbs was generated and characterized with Western blot and cell-based neutralization assay. Forty neutralizing anti-EV71 MAbs were further used to analyze the antigenic properties of 18 recent EV71 isolates representing seven genotypes in neutralization assay. We found that most neutralizing anti-EV71 MAbs are specific to conformational epitopes. We also classified the 40 neutralizing anti-EV71 MAbs into two classes according to their reactivity patterns with 18 EV71 isolates. Class I MAb can neutralize all isolates, suggesting conserved epitopes are present among EV71. Class II MAb includes four subclasses (IIa-IId) and neutralizes only subgroups of EV71 strains. Conversely, 18 EV71 strains were grouped into antigenic types 1 and four antigenic subtypes (2.1-2.4). These results suggest that the current genotyping of EV71 does not reflect their antigenicity which may be important in the selection of EV71 vaccine strains. This panel of neutralizing anti-EV71 MAbs may be useful for the recognition of emerging antigenic variants of EV71 and vaccine development.
authors.affiliation: National Institute of Diagnostics and Vaccine Development in Infectious Disease, State Key Laboratory of Cellular Stress Biology, School of Life Science, Xiamen University, Xiamen, China.
authors.forename: Yixin
authors.initials: Y
authors.lastname: Chen
authors.forename: Chuan
authors.initials: C
authors.lastname: Li
authors.forename: Delei
authors.initials: D
authors.lastname: He
authors.forename: Tong
authors.initials: T
authors.lastname: Cheng
authors.forename: Shengxiang
authors.initials: S
authors.lastname: Ge
authors.forename: James Wai-Kuo
authors.initials: JW
authors.lastname: Shih
authors.forename: Qinjian
authors.initials: Q
authors.lastname: Zhao
authors.forename: Pei-Jer
authors.initials: PJ
authors.lastname: Chen
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Ningshao
authors.initials: N
authors.lastname: Xia
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics* / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000235:genetics* / Q000276:immunology*; D000914:Antibodies, Viral / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D029821:Enterovirus A, Human / Q000235:genetics* / Q000276:immunology*; D005260:Female; D005838:Genotype; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral