Neutralizing antibody response in the patients with hand, foot and mouth disease to enterovirus 71 and its clinical implications

Yang, Chunfu; Deng, Chaoyang; Wan, Jianxin; Zhu, Liye; Leng, Qibin

doi:10.1186/1743-422x-8-306

Cited by 46 publications

(50 citation statements)

References 29 publications

(34 reference statements)

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“…To date, that is not well understood. Our data also indicated that the serum titers of specific NAb-EV71 in patients with acute stage of EV71 infection were higher than those in HC (severe or mild cases versus HC, P < 0.0001), but no significant difference was observed between mild and severe patients groups (severe versus mild cases, P = 0.9693), which corresponded to previous studies [3]. Additionally, we found that enhanced frequency of circulating CXCR5 + CD4 + TFH, PD-1 high CXCR5 + CD4 + TFH, and ICOS high CXCR5 + CD4 + TFH cells was notably positively correlated with the titres of specific NAb-EV71 in patients with EV71 infection, and a significant association was not observed between the mild and severe patients, respectively.…”

Section: Discussionsupporting

confidence: 91%

Increased Frequency of Circulating Follicular Helper T Cells in Children with Hand, Foot, and Mouth Disease Caused by Enterovirus 71 Infection

Cui

Yang

et al. 2014

Journal of Immunology Research

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Enterovirus 71 (EV71) is a major causative agent of hand, foot, and mouth disease (HFMD) in children. The role of T follicular helper (TFH) cells in EV71-infected children remains unclear in regulating humoral immunity. The frequency of circulating ICOShigh/PD-1highCXCR5+CD4+ TFH cells in the children with mild and severe EV71 infection and healthy controls (HC) was detected by flow cytometry, respectively. IL-21 and IL-6 mRNA expression and their serum levels, Bcl-6 mRNA expression, and specific neutralizing antibodies against EV71 (NAb-EV71) were measured. In the acute stage of patients with EV71 infection, increased frequencies of circulating TFH cells with ICOShigh and PD-1high expression in the mild and severe patients were observed, and the positive correlations among the frequencies of circulating TFH cells and the serum levels of IL-21, IL-6, and NAb-EV71 titres were detected, respectively. Moreover, the expressions of IL-6 and IL-21 mRNA in PBMCs from patients were also significantly higher than those of HC. However, further analysis did not reveal any significant differences between mild and severe patients. These data indicate a role of TFH cells and associated cytokines in modulating the humoral response during the pathogenesis of EV71 infection.

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Section: Discussionsupporting

confidence: 91%

Increased Frequency of Circulating Follicular Helper T Cells in Children with Hand, Foot, and Mouth Disease Caused by Enterovirus 71 Infection

Cui

Yang

et al. 2014

Journal of Immunology Research

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“…75 EV-A71 elicits humoral responses, but there is no correlation between neutralizing antibody levels and disease severity indicating that altered cellular responses such as an imbalance in Th1/Th2 and Th17/Treg subset ratios play a significant role in disease outcome and may have potential prognostic value. [76][77][78] However, the presence of EV-A71 neutralizing antibodies was found to be inversely correlated with the number of severe HFMD and the loss of maternal antibodies to be responsible for an increase in severe cases in the 1-2 y age group. 34 The presence of EV-A71 neutralizing antibodies did not reduce the incidence of infections caused by non-A71 enteroviruses.…”

Section: Clinical Presentationmentioning

confidence: 91%

Is a multivalent hand, foot, and mouth disease vaccine feasible?

Klein¹,

Chong

2015

Human Vaccines & Immunotherapeutics

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Keywords: bivalent and multivalent vaccines, coxsackievirus A16, coxsackieviruses B3 and B5, echovirus 30, epidemiology, enterovirus A (EV-A), enterovirus A71, hand, foot and mouth diseases, inactivated whole virion vaccines, monovalent, EV-A71 vaccine Enterovirus A infections are the primary cause of hand, foot and mouth disease (HFMD) in infants and young children. Although enterovirus 71 (EV-A71) and coxsackievirus A16 (CV-A16) are the predominant causes of HFMD epidemics worldwide, EV-A71 has emerged as a major neurovirulent virus responsible for severe neurological complications and fatal outcomes. HFMD is a serious health threat and economic burden across the Asia-Pacific region. Inactivated EV-A71 vaccines have elicited protection against EV-A71 but not against CV-A16 infections in large efficacy trials. The current development of a bivalent inactivated EV-A71/CV-A16 vaccine is the next step toward that of multivalent HFMD vaccines. These vaccines should ultimately include other prevalent pathogenic coxsackieviruses A (CV-A6 and CV-A10), coxsackieviruses B (B3 and B5) and echovirus 30 that often co-circulate during HFMD epidemics and can cause severe HFMD, aseptic meningitis and acute viral myocarditis. The prospect and challenges for the development of such multivalent vaccines are discussed.

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“…The lower prevalence of neutralizing Abs accompanied by higher transmission rates in children and infants indicates that neutralizing Abs are important for the prevention of EV71 infection (8,18). However, 80% of EV71-infected patients become positive for EV71-specific neutralizing Abs 1 d after the onset of illness, and the magnitude of Ab responses are not correlated with disease severity and outcome (19). In contrast, documented clues imply that cellular but not humoral immune responses are correlated with disease progression and clinical outcome (20,21).…”

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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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Neutralizing antibody response in the patients with hand, foot and mouth disease to enterovirus 71 and its clinical implications

Cited by 46 publications

References 29 publications

Increased Frequency of Circulating Follicular Helper T Cells in Children with Hand, Foot, and Mouth Disease Caused by Enterovirus 71 Infection

Increased Frequency of Circulating Follicular Helper T Cells in Children with Hand, Foot, and Mouth Disease Caused by Enterovirus 71 Infection

Is a multivalent hand, foot, and mouth disease vaccine feasible?

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

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