Abstract
Hand, foot and mouth disease, associated with enterovirus 71 (EV71) infections, has recently become an important public health issue throughout the world. Serum neutralizing antibodies are major indicators of EV71 infection and protective immunity. However, the potential for cross-reactivity of neutralizing antibodies for different EV71 genotypes and subgenotypes is unclear. Here we measured the cross-reactive neutralizing antibody titers against EV71 of different genotypes or subgenotypes in sera collected from EV71-infected children and vaccine-inoculated children in a phase III clinical trial (ClinicalTrials.gov Identifier: NCT01636245) using a new pseudovirus-based neutralization assay. Antibodies induced by EV71-C4a were cross-reactive for different EV71 genotypes, demonstrating that C4a is a good candidate strain for an EV71 vaccine. Our study also demonstrated that this new assay is practical for analyses of clinical samples from epidemiological and vaccine studies.
Highlights
Hand, foot and mouth disease (HFMD) is a common illness in children, in those less than five years of age [1]
Human sera and virus 293T cells (SV40-transfected human embryonic kidney 293 cells) and RD cells were cultured as monolayers in Dulbecco’s modified Eagle’s medium (DMEM, Sigma) supplemented with 10% fetal calf serum (FCS, TBD Co., Ltd, Tianjin, China) (10% FCS–DMEM). 293S cells stably expressing SCARB2, a receptor of Enterovirus 71 (EV71) in 293 cells were cultured as monolayers in 10% FCS–DMEM supplemented with puromycin (1.25 mg/ml, Clontech). 293T (ATCC, #CRL-3216), 293 (ATCC, #CRL1573) and RD (ATCC, #CCL-136) cells were purchased from the American Type Culture Collection (ATCC). 293T cells were used for preparation of the pseudoviruses, while 293S cells were used for pseudovirus titration and the measurement of neutralizing antibody (NtAb) titers
While raising effective cross-reactive NtAbs using a vaccine against viruses with high genetic variability, such as HIV [34,35,36] and influenza [37], can be difficult, some studies have indicated that eliciting NtAbs against one subgenotype of EV71 is likely to confer cross-neutralization against certain other subgenotypes [21,22,23,38,39]
Summary
Foot and mouth disease (HFMD) is a common illness in children, in those less than five years of age [1] Since it was first reported in 1957, several large outbreaks of HFMD have been reported in eastern and southeastern Asian countries and regions. Since 2008, increasing numbers of HFMD cases have been reported by the Chinese Center for Disease Control and Prevention with 2,713 deaths until February 2014 in China (Chinese Center for Disease Control and Prevention website: http://www.chinacdc.cn/tjsj/fdcrbbg/). These increasingly large and severe HFMD epidemics are a major public health concern in mainland China [2]. EV71 infection sometimes causes severe neurological disorders, such as aseptic meningitis, encephalitis, poliomyelitis-like paralysis and even death [5,6,7]
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