title: The cross-neutralizing activity of enterovirus 71 subgenotype c4 vaccines in healthy chinese infants and children.
abstract: BACKGROUND
  EV71 is one of major etiologic causes of hand-foot-mouth disease (HFMD) and leads to severe neurological complications in young children and infants. Recently inactivated EV71 vaccines have been developed by five manufactures and clinically show good safety and immunogenicity. However, the cross-neutralizing activity of these vaccines remains unclear, and is of particular interest because RNA recombination is seen more frequently in EV71 epidemics.
  
  
  RESULTS
  In this post-hoc study, sera from a subset of 119 infants and children in two clinical trials of EV71 subgenotype C4 vaccines (ClinicalTrials.gov Identifier: NCT01313715 and NCT01273246), were detected for neutralizing antibody (NTAb) titres with sera from infected patients as controls. Cytopathogenic effect method was employed to test NTAb against EV71 subgenotype B4, B5, C2, C4 and C5, which were prominent epidemic strains worldwide over the past decade. To validate the accuracy of the results, ELISpot assay was employed in parallel to detect NTAb in all the post-vaccine sera. After two-dose vaccination, 49 out of 53 participants in initially seronegative group and 52 out of 53 participants in initially seropositive group showed less than 4-fold differences in NTAb titers against five EV71 strains, whereas corresponding values among sera from pediatric patients recovering from EV71-induced HFMD and subclinically infected participants were 8/8 and 41/43, respectively. The geometric mean titers of participants against five subgenotypes EV71 all grew significantly after vaccinations, irrespective of the baseline NTAb titer. The relative fold increase in antibody titers (NTAb-FI) against B4, B5, C2, and C5 displayed a positive correlation to the NTAb-FI against C4.
  
  
  CONCLUSIONS
  The results demonstrated broad cross-neutralizing activity induced by two C4 EV71 vaccines in healthy Chinese infants and children. However, the degree of induced cross-protective immunity, and the potential escape evolution for EV71 still need to be monitored and researched in future for these new vaccines.
authors.affiliation: National Institutes for Food and Drug Control, Beijing, China.
authors.forename: Qunying
authors.initials: Q
authors.lastname: Mao
authors.forename: Tong
authors.initials: T
authors.lastname: Cheng
authors.forename: Fengcai
authors.initials: F
authors.lastname: Zhu
authors.forename: Jingxin
authors.initials: J
authors.lastname: Li
authors.forename: Yiping
authors.initials: Y
authors.lastname: Wang
authors.forename: Yanping
authors.initials: Y
authors.lastname: Li
authors.forename: Fan
authors.initials: F
authors.lastname: Gao
authors.forename: Lisheng
authors.initials: L
authors.lastname: Yang
authors.forename: Xin
authors.initials: X
authors.lastname: Yao
authors.forename: Jie
authors.initials: J
authors.lastname: Shao
authors.forename: Ningshao
authors.initials: N
authors.lastname: Xia
authors.forename: Zhenglun
authors.initials: Z
authors.lastname: Liang
authors.forename: Junzhi
authors.initials: J
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000276:immunology; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D029821:Enterovirus A, Human / Q000235:genetics / Q000276:immunology*; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D014765:Viral Vaccines / Q000276:immunology*; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D014765:Viral Vaccines