Yan Xuemei, Liu Yuanhua, Chen Fengkun, Chang Zhaorui, Zhang Zhijie, Pons-Salort Margarita, Grassly Nicholas C
MRC Centre for Global Infectious Disease Analysis, School of Public Health, Imperial College London, London, United Kingdom.
Department of Epidemiology and Health Statistics, School of Public Health, Fudan University, Shanghai, China.
PLoS One. 2025 May 22;20(5):e0323782. doi: 10.1371/journal.pone.0323782. eCollection 2025.
Enterovirus A71 (EV-A71) is a major cause of severe hand, foot, and mouth disease (HFMD) among children in the Asia-Pacific region. Here we review randomised clinical trial data and post-licensure effectiveness studies of inactivated EV-A71 vaccines following their development and licensure in China since late 2015. We searched PubMed, Web of Science Core Collection, Elsevier ScienceDirect, China National Knowledge Infrastructure (CNKI), and Wanfang Data on 20 May 2024 with no date restriction in English and Mandarin, using key terms including "EV-A71", "enterovirus 71", "hand, foot, and mouth disease", "HFMD", "vaccine", "efficacy", "effectiveness", "protection" and "impact". Phase III randomized controlled trials (RCTs) reporting vaccine efficacy and observational studies on effectiveness were eligible for inclusion. We excluded studies that evaluated non-laboratory confirmed HFMD associated outcomes, abstracts, reviews, comments, animal studies, cross-sectional studies, and modelling studies. Summary measures of vaccine efficacy and effectiveness were based on random-effects models. After screening, 14 articles were eligible for inclusion, including 6 reporting 4 different phase III RCTs. Estimated efficacy of 2 doses of EV-A71 vaccine against EV-A71 associated HFMD 1 year after vaccination ranged from 90.0% to 97.9%, with an overall estimate for all products of 95.6% (95% Confidence Interval: 92.1, 97.5). Efficacy remained high at 26 months post-vaccination, ranging from 94.7% to 94.8%. The estimated overall effectiveness of 2-dose vaccination against any EV-A71-HFMD across five test-negative case-control studies was 84.3% (95% CI: 75.2, 90.0) among children aged 0-12 years. Effectiveness was higher in older children compared to younger children (85.3% (72.9, 92.1) vs. 79.8% (61.2, 89.5)) and higher against severe compared with non-severe EV-A71-HFMD (90.0% (80.0, 95.0) vs. 76.5% (50.0, 89.0)). The effectiveness declined in more recent studies with longer follow-up. Inactivated EV-A71 vaccines offer a high level of protection against EV-A71 HFMD. Longer term studies are needed to evaluate the persistence of protection beyond 2 years post-vaccination.
肠道病毒A71型（EV - A71）是亚太地区儿童严重手足口病（HFMD）的主要病因。在此，我们回顾了自2015年末在中国研发和获批以来，灭活EV - A71疫苗的随机临床试验数据及获批后的有效性研究。我们于2024年5月20日在PubMed、科学网核心合集、爱思唯尔ScienceDirect、中国知网（CNKI）和万方数据中进行检索，不限英文和中文文献的日期，使用的关键词包括“EV - A71”、“肠道病毒71型”、“手足口病”、“HFMD”、“疫苗”、“效力”、“有效性”、“保护”和“影响”。报告疫苗效力的III期随机对照试验（RCT）以及关于有效性的观察性研究均符合纳入标准。我们排除了评估非实验室确诊的HFMD相关结局的研究、摘要、综述、评论、动物研究、横断面研究和模型研究。疫苗效力和有效性的汇总指标基于随机效应模型。筛选后，有14篇文章符合纳入标准，其中6篇报告了4项不同的III期RCT。接种疫苗1年后，2剂EV - A71疫苗针对EV - A71相关HFMD的估计效力在90.0%至97.9%之间，所有产品的总体估计效力为95.6%（95%置信区间：92.1，97.5）。接种疫苗26个月后效力仍维持在较高水平，范围为94.7%至94.8%。在五项检测阴性病例对照研究中，2剂疫苗接种针对0至12岁儿童任何EV - A71 - HFMD的估计总体有效性为84.3%（95%CI：75.2，90.0）。年龄较大儿童的有效性高于年龄较小儿童（85.3%（72.9，92.1）对79.8%（61.2, 89.5）），针对重症EV - A71 - HFMD的有效性高于非重症（90.0%（80.0，95.0）对76.5%（50.0，89.0））。在随访时间更长的近期研究中，有效性有所下降。灭活EV - A71疫苗对EV - A71 HFMD提供了高水平的保护。需要进行更长期的研究来评估接种疫苗2年后保护作用的持久性。
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