The cross-neutralizing activity of enterovirus 71 subgenotype c4 vaccines in healthy chinese infants and children.
The cross-neutralizing activity of enterovirus 71 subgenotype c4 vaccines in healthy chinese infants and children.
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DOI：
10.1371/journal.pone.0079599
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Mao Q;Cheng T;Zhu F;Li J;Wang Y;Li Y;Gao F;Yang L;Yao X;Shao J;Xia N;Liang Z;Wang J
EV71是手足口病(HFMD)的主要病原之一，可导致婴幼儿严重的神经系统并发症。近年来，已有5家生产厂家研制出EV71灭活疫苗，临床应用表明具有良好的安全性和免疫原性。然而，这些疫苗的交叉中和活性仍不清楚，特别令人感兴趣的是，因为RNA重组在EV71流行中更常见。在这项特别后研究中，检测了两项EV71亚型C4疫苗临床试验(ClinicalTrials.gov标识：NCT01313715和NCT01273246)中119名婴儿和儿童的血清中和抗体(NTAb)滴度，并以感染患者的血清为对照。采用细胞病变效应法检测近10年来世界流行的EV71亚型B4、B5、C2、C4和C5的NTAb。为了验证结果的准确性，采用ELISpot法平行检测所有疫苗后血清中的NTAb。接种两剂疫苗后，53例初阴组中49例和53例初阳性组中52例对5株EV71株的NTAb滴度相差不到4倍，而EV71感染手足口病恢复期患儿和亚临床感染者的NTAb滴度分别为8/8和41/43。无论基线NTAb滴度如何，接种疫苗后，参与者对五种亚型EV71的几何平均滴度均显著增加。抗B4、B5、C2和C5抗体滴度(NTAb-FI)的相对倍数增加与抗C4的NTAb-FI呈正相关。结果表明，两种C4EV71疫苗对中国健康婴幼儿具有广泛的交叉中和活性。然而，这些新疫苗的诱导交叉保护免疫的程度以及EV71的潜在逃逸进化仍需在未来进行监测和研究。
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.
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