Enterovirus 71 Infection of Monocytes with Antibody-Dependent Enhancement

Wang, Shih Min; Chen, I. Chun; Ling, Su; Huang, Kao Jean; Lei, Huan Yao; Liu, Ching Chuan

doi:10.1128/cvi.00108-10

Cited by 47 publications

(40 citation statements)

References 43 publications

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“…In these patients, the ADE of CVB3 infection would predominate over CVB3 neutralization [27]. We demonstrated that subneutralizing antibodies of EV71 bind to it and enhance the virus uptake of Fc receptor-bearing monocytes in vitro [28]. We also showed the same phenomenon in a mice model of EV71 infection.…”

Section: Discussionsupporting

confidence: 64%

Reemerging of enterovirus 71 in Taiwan: the age impact on disease severity

Wang

Lin³

et al. 2011

Eur J Clin Microbiol Infect Dis

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Enterovirus 71 (EV71) infection commonly strike children under the age of 3 years, with an occasionally unfavorable outcome in children. This study was designed to explore the relationship between age and the severity of complications, which may associate with antibody-dependent enhancement (ADE) in EV71. All EV71-infected patients during the outbreak of 2008 were recruited. In total, 134 patients were enrolled and categorized into two age groups, 0-12 months (n = 18) and >12 months (n = 116). Pulmonary edema/hemorrhage more commonly occur in patients younger than 12 months. No difference in the occurrence of herpangina/hand-foot-and-mouth disease (HFMD), uncomplicated brainstem encephalitis (BE), or autonomic nervous system (ANS) dysregulation was noted between the two age groups. Patients with pulmonary edema/hemorrhage (11.9 ± 14.7 months) were younger than patients with herpangina/HFMD (35.8 ± 26.4 months) or ANS dysregulation (33.9 ± 20.9 months). Our findings are in agreement with the data regarding the outbreak in Taiwan, in which a decrease in age corresponded to an increase in disease severity with regard to central nervous system complications. A reduction of maternal antibodies to the subneutralizing level within 1 year of age may be associated with the ADE of the infection. This study could provide possible clinical significance with regard to ADE phenomena in young infants infected by EV71.

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Section: Discussionsupporting

confidence: 64%

Reemerging of enterovirus 71 in Taiwan: the age impact on disease severity

Wang

Lin³

et al. 2011

Eur J Clin Microbiol Infect Dis

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“…Previous studies demonstrate that subneutralizing Abs may be correlated with Ab-dependent enhancement in EV71 infection (44)(45)(46). Thus, T cells that are essential in the selection and maturation of high-affinity Abs deserve more attention for immunological investigation, and a comprehensive knowledge of EV71 T cell immunity would benefit our understanding of host protection mechanisms against EV71 (47).…”

Section: Discussionmentioning

confidence: 99%

VP2 Dominated CD4+ T Cell Responses against Enterovirus 71 and Cross-Reactivity against Coxsackievirus A16 and Polioviruses in a Healthy Population

Tan

Sun

et al. 2013

The Journal of Immunology

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Enterovirus 71 (EV71)–associated hand-foot-mouth disease has become a major threat to public health in the Asia–Pacific region. Although T cell immunity is closely correlated with clinical outcomes of EV71 infection, little is known about T cell immunity baseline against EV71 and T cell immunogenecity of EV71 Ags in the population, which has restricted our understanding of immunoprotection mechanisms. In this study, we investigated the cellular immune responses against the four structural Ags of EV71 and determined the immunohierarchy of these Ags in healthy adults. A low frequency of EV71-responsive T cells was detected circulating in peripheral blood, and broad T cell immune responses could be identified in most of the subjects after in vitro expansion. We demonstrated that the VP2 Ag with broad distribution of immunogenic peptides dominates T cell responses against EV71 compared with VP1, VP3, and VP4. Furthermore, the responses were illuminated to be mainly single IFN-γ–secreting CD4+ T cell dependent, indicating the previous natural acute viral infection of the adult population. Conservancy analysis of the immunogenic peptides revealed that moderately variant peptides were in the majority in coxsackievirus A16 (CV-A16) whereas most of the peptides were highly variant in polioviruses. Less efficient cross-reactivity against CV-A16 might broadly exist among individuals, whereas influences derived from poliovirus vaccination would be limited. Our findings suggest that the significance of VP2 Ag should be addressed in the future EV71-responsive immunological investigations. And the findings concerning the less efficient cross-reactivity against CV-A16 and limited influences from poliovirus vaccination in EV71-contacted population would contribute to a better understanding of immunoprotection mechanisms against enteroviruses.

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“…Antibody-based therapy has been well demonstrated in animal experiments and clinical practice [7]–[11]. However, a phenomenon termed antibody-dependent enhancement (ADE) was recently confirmed in experimental and clinical settings [12], [13]. Sub-neutralizing concentration of antibodies was evidenced to enhance EV71 infection in Fc receptor-bearing human monocytes and contributed to exacerbation of EV71 infection in mice.…”

Section: Introductionmentioning

confidence: 99%

Human IgG Subclasses against Enterovirus Type 71: Neutralization versus Antibody Dependent Enhancement of Infection

et al. 2013

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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.

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Enterovirus 71 Infection of Monocytes with Antibody-Dependent Enhancement

Cited by 47 publications

References 43 publications

Reemerging of enterovirus 71 in Taiwan: the age impact on disease severity

Reemerging of enterovirus 71 in Taiwan: the age impact on disease severity

VP2 Dominated CD4+ T Cell Responses against Enterovirus 71 and Cross-Reactivity against Coxsackievirus A16 and Polioviruses in a Healthy Population

Human IgG Subclasses against Enterovirus Type 71: Neutralization versus Antibody Dependent Enhancement of Infection

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