Hand, foot, and mouth disease (HFMD) is a pediatric public health concern in Asia. Surveillance data on the circulating serotypes of HFMD suggest that Enterovirus A71 (EV-A71) and coxsackieviruses A6, A10, and A16 (CVA6, CVA10, and CVA16) are the major serotypes causing HFMD. Asian countries, including Korea, are currently developing a multivalent vaccine targeting these serotypes. However, the immunity of children against specific serotypes, indicating past infection, should also be considered while selecting candidate serotypes for vaccine development. Therefore, we aimed to identify the age-stratified serological statuses of Korean children to determine candidate serotypes for HFMD vaccine development. This study included 220 participants, categorized into four age groups, 7 months–2 years, 3–5 years, 6–10 years, and 11–15 years. A neutralization test was performed to quantitate the neutralizing antibodies (NtAbs) in the sera of the participants. Only EV-A71 and CVA6 were found suitable as candidate serotypes for vaccine development, whereas further study is needed for CVA10 and CVA16. The highest seropositivity and NtAb titer ranges were observed for CVA6 in all age groups, suggesting that the participants had been predominantly exposed to CVA6. For EV-A71, seropositivity and NtAb titer ranges steadily increased with age, suggesting that children were currently exposed to EV-A71. For CVA10, the 3–5 years group showed the highest seropositivity rate and higher NtAb titer ranges than the older age groups, indicating that the exposure to CVA10 had mainly occurred in recent years. Future studies will identify whether the exposure to CVA10 was transient or will continue. For CVA16, seropositivity and NtAb titer ranges were generally low, indicating that only a few participants had been exposed to CVA16. We identified discrepancies between the sentinel surveillance data and our findings. This study provides a new perspective for HFMD vaccine development and policy making in Asian countries.

中文翻译：

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韩国儿童肠道病毒疫苗候选血清型中和抗体的血清阳性率

手足口病 (HFMD) 是亚洲的儿科公共卫生问题。手足口病流行血清型的监测数据表明，肠道病毒A71 (EV-A71) 和柯萨奇病毒 A6、A10 和 A16（CVA6、CVA10 和 CVA16）是导致手足口病的主要血清型。包括韩国在内的亚洲国家目前正在开发针对这些血清型的多价疫苗。然而，在选择用于疫苗开发的候选血清型时，还应考虑儿童对特定血清型的免疫力，这表明过去曾感染过。因此，我们旨在确定韩国儿童的年龄分层血清学状态，以确定手足口病疫苗开发的候选血清型。这项研究包括 220 名参与者，分为四个年龄组，7 个月至 2 岁、3-5 岁、6-10 岁和 11-15 岁。进行中和测试以量化参与者血清中的中和抗体 (NtAbs)。只有 EV-A71 和 CVA6 被发现适合作为疫苗开发的候选血清型，而 CVA10 和 CVA16 需要进一步研究。在所有年龄组中观察到 CVA6 的最高血清阳性和 NtAb 滴度范围，表明参与者主要暴露于 CVA6。对于 EV-A71，血清阳性和 NtAb 滴度范围随着年龄的增长而稳步增加，这表明儿童目前暴露于 EV-A71。对于 CVA10，3-5 岁组的血清阳性率最高，NtAb 滴度范围高于老年组，表明 CVA10 的暴露主要发生在近年来。未来的研究将确定暴露于 CVA10 是暂时的还是将继续。对于 CVA16，血清阳性和 NtAb 滴度范围普遍较低，表明只有少数参与者接触过 CVA16。我们发现哨点监测数据与我们的发现之间存在差异。该研究为亚洲国家手足口病疫苗的开发和政策制定提供了新的视角。