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The cross-neutralizing activity of enterovirus 71 subgenotype c4 vaccines in healthy chinese infants and children.

ABSTRACT: 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.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.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.

SUBMITTER: Mao Q

PROVIDER: S-EPMC3834186 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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The cross-neutralizing activity of enterovirus 71 subgenotype c4 vaccines in healthy chinese infants and children.

Mao Qunying Q Cheng Tong T Zhu Fengcai F Li Jingxin J Wang Yiping Y Li Yanping Y Gao Fan F Yang Lisheng L Yao Xin X Shao Jie J Xia Ningshao N Liang Zhenglun Z Wang Junzhi J

PloS one 20131119 11

<h4>Background</h4>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.<h4>Methodology/principal fin ...[more]

PMID: 24260259

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Project description:Background: Subgenotype C4 of enterovirus 71 (EV71) is the predominant agent of Hand Foot and Mouth disease (HFMD) circulating in the mainland of China. For the first time, a subgenotype C2 of EV71 named SY30-2 was isolated from a HFMD case in Beijing, China. Since it is uncertain whether antibodies raised against subgenotype C4 of EV71 can protect C2 EV71, it is important to monitor and check the presence of cross-reactive antibodies against new EV71 subgenotypes. To find out the causes for the different NtAb, this study is to investigate the relationships between amino acid residue variations and cross-reactive antibodies against EV71 subgenotypes C2 and C4. Methods: Nucleotide and amino acid sequences from full-length genome sequence of SY30-2 were compared to EV71 reference strains. A microneutralization test was used to detect neutralizing antibody (NTAb) in the sera of subgenotype C4 of EV71 infected cases against SY30-2 and FY17 (a C4 isolate). The 3D structure of the viral capsid protein of SY30-2 was constructed. Results: Genome sequence and similarity plot analyses showed that SY30-2 shared the highest identity with subgenotype C2 of EV71 strains in every fragment of the genome. While the microneutralization test result showed that children infected with subgenotype C4 of EV71 had higher NTAb titers against FY17 than SY30-2 (p < 0.001). The amino acid sequence comparison revealed that four amino acid residues VP1-22, VP1-31, VP1-249 and VP3-93 were highly conserved in subgenotype C4 of EV71 compared with the corresponding amino acid residues on subgenotype C2 of EV71 (p < 0.05). Furthermore, the 3D-structure of viral capsid protein showed that VP1-22, VP1-31 and VP3-93 were located on the surface of virion. Conclusion: This is the first report of an EV71 subgenotype C2 isolated from HFMD in Beijing, China. Only a few antigenic variations on subgenotype C2 of EV71 could have led to a great decrease in NTAb titer. Thus, imported new genotypes and subgenotypes of EV71 should be closely monitored. The efficacy of available vaccines against new viruses should be evaluated as well.

Dataset Information

The cross-neutralizing activity of enterovirus 71 subgenotype c4 vaccines in healthy chinese infants and children.

Publications

The cross-neutralizing activity of enterovirus 71 subgenotype c4 vaccines in healthy chinese infants and children.

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