Cross-reactive neutralizing antibody responses to enterovirus 71 infections in young children: implications for vaccine development.
Cross-reactive neutralizing antibody responses to enterovirus 71 infections in young children: implications for vaccine development.
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DOI：
10.1371/journal.pntd.0002067
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发表时间：
2013
影响因子：
3.8
通讯作者：
Lee MS
中科院分区：
文献类型：
--
作者：
Huang ML;Chiang PS;Chia MY;Luo ST;Chang LY;Lin TY;Ho MS;Lee MS
最近，肠病毒71型（EV 71）在亚洲儿童中引起危及生命的爆发，涉及神经和心肺并发症，其机制不明。EV 71具有单一血清型，但在遗传学上可分为3个主要基因组（A、B和C）和11种基因型（A、B1、B5和C1、C5）。在台湾，全国性EV 71流行以不同的优势基因型发生在1998年（C2），2000-2001年（B4），2004-2005年（C4）和2008年（B5）。在这项研究中，收集血清以测量针对不同基因型的交叉反应性中和抗体滴度。我们收集了1998年、2000年、2005年、2008年或2010年发生EV 71感染的儿童的历史血清，并测量了针对所有11种EV 71基因型的交叉反应性中和抗体滴度。此外，我们还对供试病毒的P1蛋白的氨基酸序列进行了比对和比较。血清学数据显示，感染基因组B和C的儿童对基因组A的中和抗体滴度始终较低（差异>4倍）。序列比较显示，5个氨基酸特征（VP 2中的N143 D; VP 1中的K18 R、H116 Y、D167 E和S275 A）对基因组A具有特异性，并且可能与观察到的抗原变异相关。本研究记录了不同EV 71基因组之间的抗原变异，并确定了潜在的免疫显性氨基酸位置。肠道病毒监测和疫苗开发应监测这些职位。最近，肠病毒71型（EV 71）在亚洲热带地区引起了危及生命的疫情。EV 71具有单一血清型，但在遗传学上可分为3个主要基因组和11种基因型（A、B1、B5和C1、C5）。在台湾，全国性EV 71流行以不同的优势基因型发生在1998年（C2），2000-2001年（B4），2004-2005年（C4）和2008年（B5）。在这项研究中，收集了感染这4种基因型的儿童的历史血清，以测量针对11种基因型的交叉反应性中和抗体滴度。此外，还比较了供试病毒P1蛋白的氨基酸序列。血清学数据显示，感染基因组B和C的儿童对基因组A的中和抗体滴度始终较低（差异>4倍）。基因组B和C之间的抗原变异可以检测到，但没有明确的模式。五个氨基酸特征是基因组A特异性的，可能与观察到的抗原变异有关。疫苗开发应监测抗原和遗传变异以选择疫苗株。
Recently, enterovirus 71 (EV71) has caused life-threatening outbreaks involving neurological and cardiopulmonary complications in Asian children with unknown mechanism. EV71 has one single serotype but can be phylogenetically classified into 3 main genogroups (A, B and C) and 11 genotypes (A, B1∼B5 and C1∼C5). In Taiwan, nationwide EV71 epidemics with different predominant genotypes occurred in 1998 (C2), 2000–2001 (B4), 2004–2005 (C4), and 2008 (B5). In this study, sera were collected to measure cross-reactive neutralizing antibody titers against different genotypes. We collected historical sera from children who developed an EV71 infection in 1998, 2000, 2005, 2008, or 2010 and measured cross-reactive neutralizing antibody titers against all 11 EV71 genotypes. In addition, we aligned and compared the amino acid sequences of P1 proteins of the tested viruses. Serology data showed that children infected with genogroups B and C consistently have lower neutralizing antibody titers against genogroup A (>4-fold difference). The sequence comparisons revealed that five amino acid signatures (N143D in VP2; K18R, H116Y, D167E, and S275A in VP1) are specific for genogroup A and may be related to the observed antigenic variations. This study documented antigenic variations among different EV71 genogroups and identified potential immunodominant amino acid positions. Enterovirus surveillance and vaccine development should monitor these positions. Recently, enterovirus 71 (EV71) has caused life-threatening outbreaks in tropical Asia. EV71 has one single serotype but can be phylogenetically classified into 3 main genogroups and 11 genotypes (A, B1∼B5 and C1∼C5). In Taiwan, nationwide EV71 epidemics with different predominant genotypes occurred in 1998(C2), 2000–2001(B4), 2004–2005(C4), and 2008(B5). In this study, historical sera from children infected with these 4 genotypes were collected to measure cross-reactive neutralizing antibody titers against 11 genotypes. In addition, amino acid sequences of P1 proteins of the tested viruses were compared. Serology data showed that children infected with genogroup B and C consistently have lower neutralizing antibody titers against genogroup A (>4-fold difference). Antigenic variations between genogroup B and C could be detected but did not have a clear pattern. Five amino acid signatures are specific for genogroup A and may be related to the observed antigenic variations. Vaccine development should monitor the antigenic and genetic variations to select vaccine strains.
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