title: Human IgG subclasses against enterovirus Type 71: neutralization versus antibody dependent enhancement of infection.
abstract: The emerging human enterovirus 71 (EV71) represents a growing threat to public health, and no vaccine or specific antiviral is currently available. Human intravenous immunoglobulin (IVIG) is clinical used in treating severe EV71 infections. However, the discovery of antibody dependent enhancement (ADE) of EV71 infection illustrates the complex roles of antibody in controlling EV71 infection. In this study, to identify the distinct role of each IgG subclass on neutralization and enhancement of EV71 infection, different lots of pharmaceutical IVIG preparations manufactured from Chinese donors were used for IgG subclass fractionation by pH gradient elution with the protein A-conjugated affinity column. The neutralization and ADE capacities on EV71 infection of each purified IgG subclass were then assayed, respectively. The neutralizing activity of human IVIG is mainly mediated by IgG1 subclass and to less extent by IgG2 subclass. Interestingly, IgG3 fraction did not have neutralizing activity but enhanced EV71 infection in vitro. These results revealed the different roles of human IgG subclasses on EV71 infection, which is of critical importance for the rational design of immunotherapy and vaccines against severe EV71 diseases.
authors.affiliation: Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
authors.forename: Rui-Yuan
authors.initials: RY
authors.lastname: Cao
authors.forename: Da-Yong
authors.initials: DY
authors.lastname: Dong
authors.forename: Rui-Ju
authors.initials: RJ
authors.lastname: Liu
authors.forename: Jian-Feng
authors.initials: JF
authors.lastname: Han
authors.forename: Guang-Chuan
authors.initials: GC
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Li
authors.forename: Yong-Qiang
authors.initials: YQ
authors.lastname: Deng
authors.forename: Shun-Ya
authors.initials: SY
authors.lastname: Zhu
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Wang
authors.forename: Fang
authors.initials: F
authors.lastname: Lin
authors.forename: Fu-Jun
authors.initials: FJ
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: E-De
authors.initials: ED
authors.lastname: Qin
authors.forename: Cheng-Feng
authors.initials: CF
authors.lastname: Qin
mesh_terms: D057134:Antibodies, Neutralizing / Q000302:isolation & purification / Q000502:physiology*; D000914:Antibodies, Viral / Q000302:isolation & purification / Q000502:physiology*; D045744:Cell Line, Tumor; D029821:Enterovirus A, Human / Q000276:immunology*; D004769:Enterovirus Infections / Q000276:immunology* / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D007074:Immunoglobulin G / Q000302:isolation & purification / Q000502:physiology*; D009500:Neutralization Tests
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007074:Immunoglobulin G