手足口病EV71疫苗研究发布新成果 发布时间：2013-2-26 来源：药品资讯网信息中心近日，《柳叶刀》杂志在线发表题为《肠道病毒71型疫苗在中国健康幼儿和婴幼儿中的免疫原性和安全性：随机、双盲、安慰剂对照Ⅱ期临床试验》的研究论文，介绍中国新型手足口病EV71疫苗的Ⅱ期临床研究成果。美国CDC国家传染病中心肠道病毒中心主任Pallansch博士在同期《柳叶刀》杂志为该研究论文发表专业评论，充分肯定EV71疫苗Ⅱ期临床试验在疫苗的剂量、剂型和免疫程序上取得的成果，并对即将完成的该疫苗Ⅲ期临床试验寄予厚望。 此项研究由江苏省疾病预防控制中心、中国食品药品检定研究院、中国生物技术股份有限公司北京微谷生物医药有限公司等单位合作开展，探讨了疫苗人体免疫后的中和抗体转归，发现接种后第8个月抗体滴度出现显著降低，提出进行加强免疫的必要性；证明婴幼儿常规接种口服脊髓灰质炎疫苗未对接种EV71疫苗的免疫应答产生干扰；血清学研究结果支持开展Ⅲ期临床试验；提出适用于我国6个月~36个月龄婴幼儿和幼儿的适宜剂量和剂型为采用320U剂量佐剂疫苗2针免疫程序。 据悉，此项研究得到国家重大传染病和重大新药创新专项和支撑计划的支持。为保证EV71疫苗研发的顺利进行，中国食品药品检定研究院等相关单位研制了国家抗原定量标准品和标准化的临床样本检测技术，解决了临床样本检测标准化等难题。
Immunogenicity and safety of an enterovirus 71 vaccine in healthy Chinese children and infants: a randomised, double-blind, placebo-controlled phase 2 clinical trial The Lancet, Early Online Publication, 24 January 2013
Background Enterovirus 71 (EV71) outbreaks are a socioeconomic burden, especially in the western Pacific region. Results of phase 1 clinical trials suggest an EV71 vaccine has a clinically acceptable safety profile and immunogenicity. We aimed to assess the best possible dose and formulation, immunogenicity, and safety profile of this EV71 vaccine in healthy Chinese children.
Methods This randomised, double-blind, placebo-controlled, phase 2 trial was undertaken at one site in Donghai County, Jiangsu Province, China. Eligible participants were healthy boys or girls aged 6—36 months. Participants were randomly assigned (1:1:1:1:1) to receive either 160 U, 320 U, or 640 U alum-adjuvant EV71 vaccine, 640 U adjuvant-free EV71 vaccine, or a placebo (containing alum adjuvant only), according to a blocked randomisation list generated by SAS 9.1. Participants and investigators were masked to the assignment. The primary endpoint was anti-EV71 neutralising antibody geometric mean titres (GMTs) at day 56, analysed according to protocol. The study is registered with ClinicalTrials.gov, number NCT01399853.
Findings We randomly assigned 1200 participants, 240 (120 aged 6—11 months [infants] and 120 aged 12—36 months [children]) of whom were assigned to each dose. 1106 participants completed the study and were included in the according-to-protocol analysis. The main reasons for dropout were withdrawal of consent and refusal to donate a blood sample. Infants who received the 640 U adjuvant vaccine had the highest GMTs on day 56 (742·2 [95% CI 577·3—954·3]), followed by those who received the 320 U formulation (497·9 [383·1—647·0]). For children, those who received the 320 U formulation had the highest GMTs on day 56 (1383·2 [1037·3—1844·5]). Participants who received the vaccine had significantly higher GMTs than did who received placebo (p<0·0001). For the subgroup of participants who were seronegative at baseline, both infants and children who received the 640 U adjuvant vaccine had the highest GMTs on day 56 (522·8 [403·9—676·6] in infants and 708·4 [524·1—957·6] in children), followed by those who received the 320 U adjuvant vaccine (358·2 [280·5—457·5] in infants and 498·0 [383·4—646·9] in children). 549 (45·8%) of 1200 participants (95 CI 42·9—48·6%) reported at least one injection-site or systemic adverse reaction, but the incidence of adverse reactions did not differ significantly between groups (p=0·36). The 640 U alum-adjuvant vaccine group had a significantly higher incidence of induration than did the 640 U adjuvant-free group (p=0·001).
Interpretation Taking immunogenicity, safety, and production capacity into account, the 320 U alum-adjuvant formulation of the EV71 vaccine is probably the best possible formulation for phase 3 trials.
Funding The National Science and Technology Major Project (2011ZX10004-902) of the Chinese Ministry of Science and Technology, China's 12—5 National Major Infectious Disease Program (2012ZX10002-001), and Beijing Vigoo Biological.
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