Liu Longding, Mo Zhaojun, Liang Zhenglun, Zhang Ying, Li Rongcheng, Ong Kien Chai, Wong Kum Thong, Yang Erxia, Che Yanchun, Wang Jingjing, Dong Chenghong, Feng Min, Pu Jing, Wang Lichun, Liao Yun, Jiang Li, Tan Soon Hao, David Perera, Huang Teng, Zhou Zhenxin, Wang Xuanyi, Xia Jielai, Guo Lei, Wang Ling, Xie Zhongping, Cui Wei, Mao Qunying, Liang Yan, Zhao Hongling, Na Ruixiong, Cui Pingfang, Shi Haijing, Wang Junzhi, Li Qihan
Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China.
Guangxi Province Centres for Disease Control and Prevention, Nanning, China.
BMC Med. 2015 Sep 17;13:226. doi: 10.1186/s12916-015-0448-7.
To investigate the long-term effects on immunity of an inactivated enterovirus 71 (EV71) vaccine and its protective efficacy.
A sub-cohort of 1,100 volunteers from Guangxi Province in China was eligible for enrolment and randomly administered either the EV71 vaccine or a placebo on days 0 and 28 in a phase III clinical trial and then observed for the following 2 years with approval by an independent ethics committee of Guangxi Zhuang Autonomous Region, China. Serum samples from the 350 participants who provided a full series of blood samples (at all the sampling points) within the 2-year period were collected. Vaccine-induced immune effects, including the neutralizing antibody titres and cross-protection against different genotypes of EV71, were examined. This study also evaluated the protective efficacy of this vaccine based upon clinical diagnosis.
This sub-cohort showed a >60% drop-out rate over 2 years. The seroconversion rates among the 161 immunized subjects remained >95% at the end of study. The geometric mean titres of neutralizing antibodies (anti-genotype C4) 360 days after vaccination in 350 subjects were 81.0 (subjects aged 6-11 months), 98.4 (12-23 months), 95.0 (24-35 months), and 81.8 (36-71 months). These titres subsequently increased to 423.1, 659.0, 545.0, and 321.9, respectively, at 540 days post-immunization (d.p.i.), and similar levels were maintained at 720 d.p.i. Higher IFN-γ/IL-4-specific responses to the C4 genotype of EV71 and cross-neutralization reactivity against major EV71 genotype strains were observed in the vaccine group compared to those in the placebo group. Five EV71-infected subjects were observed in the placebo-treated control group and none in the vaccine-immunized group in per-protocol analysis.
These results are consistent with the induction of dynamic immune responses and protective efficacy of the vaccine against most circulating EV71 strains.
Clinicaltrials.gov, NCT01569581, Trial registration date: March 2012.
研究肠道病毒71型（EV71）灭活疫苗对免疫力的长期影响及其保护效力。
在中国广西的1100名志愿者亚队列符合入组条件，并在一项III期临床试验的第0天和第28天随机接种EV71疫苗或安慰剂，随后在中国广西壮族自治区独立伦理委员会批准下进行为期2年的观察。收集了2年内提供了完整系列血样（在所有采样点）的350名参与者的血清样本。检测了疫苗诱导的免疫效应，包括中和抗体滴度和对不同基因型EV71的交叉保护作用。本研究还基于临床诊断评估了该疫苗的保护效力。
该亚队列在2年内的失访率超过60%。161名免疫受试者在研究结束时的血清转化率仍>95%。350名受试者在接种疫苗360天后的中和抗体（抗C4基因型）几何平均滴度分别为6-11月龄组81.0、12-23月龄组98.4、24-35月龄组95.0和36-71月龄组81.8。这些滴度在免疫后540天（d.p.i.）分别升至423.1、659.0、545.0和321.9，并在720 d.p.i.维持相似水平。与安慰剂组相比，疫苗组对EV71 C4基因型有更高的IFN-γ/IL-4特异性应答以及对主要EV71基因型毒株的交叉中和反应性。符合方案分析中，安慰剂治疗的对照组观察到5名EV71感染受试者，疫苗免疫组未观察到。
这些结果与疫苗诱导动态免疫反应及对大多数流行的EV71毒株的保护效力一致。
Clinicaltrials.gov，NCT01569581，试验注册日期：2012年3月。
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