中国埃博拉疫苗在非洲研究再获重大突破

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军事医学科学院12月28日宣布，由该院生物工程研究所陈薇研究员团队研发的重组埃博拉疫苗（rAd5-EBOV），在非洲塞拉利昂开展的Ⅱ期500例临床试验取得成功，这是我国疫苗研究首次走出国门后的历史性突破。12月23日凌晨，国际著名医学杂志《柳叶刀》（The Lancet）在线发布了相关科研论文。

在科技部、国家卫计委和军委后勤保障部等重点资助和合作方天津康希诺生物技术有限公司全程参与下，经过国家食品药品监督管理局启动特别评审程序，该疫苗已于两年前进入临床阶段。2015年5月，研究团队开启了赴埃博拉疫情最严重的西非国家——塞拉利昂的临床注册工作，并得到了中国驻塞拉利昂大使馆和中国疾病预防控制中心驻塞生物安全实验室的大力支持。经过严苛的知识产权审查、多轮的技术资料审评、会议答辩和现场考核，终于通过了伦理和临床许可，实现了中国疫苗在境外临床试验的“零突破”。

疫苗临床试验由江苏省疾病预防控制中心朱凤才主任医师与塞方卫生部阿里·乌瑞博士共同主持，体现了良好的国际合作，临床方案为剂量递增、随机盲法、安慰剂对照，试验结果表明，与2014年在中国境内的临床研究结果一致，我国研制的重组疫苗安全性好，接种后14天产生高水平抗体，28天达到峰值，提前２周接种可以实现免疫保护。

据了解，我国研制的重组埃博拉疫苗，为全球首个2014基因型，针对性强，且首创冻干粉剂型，37℃环境下可稳定存储3周以上，适合应急条件下的广泛使用，现已具备大规模生产技术条件。此前，2014年12月，该疫苗在泰州中国医药城进行了中国人群Ⅰ期临床试验，共招募120名志愿者，相关研究结果于2015年3月24日发表在《柳叶刀》。2015年4月，李兰娟院士牵头在浙江大学第一附属医院开展了在华非洲人Ⅰ期临床试验，共招募61名志愿者，为我国境内开展的首个针对非中国人群的临床试验。

此次，《柳叶刀》杂志再次刊发中国疫苗在该领域的相关研究成果，同期也刊发了WHO牵头在几内亚开展的埃博拉疫苗（rVSV-EBOV）相关工作，还于同一天在《柳叶刀·全球健康》（The Lancet Global Health）刊发了中国人群疫苗加强免疫后产生高水平免疫反应并长时间持续的研究结果，标志着我国应急疫苗研发水平得到国际同行的高度认可。面对致死率最高、传播范围广泛、全球严重恐慌的埃博拉疫情，我国科学家取得的完全具有自主知识产权的相关成果，既展示了我国生物医药领域科技创新的实力跃升，也是我国防控烈性传染病疫情能力的一次实战检验，对国家生物安全具有重要战略意义。


来源：科学网

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Safety and immunogenicity of a recombinant adenovirus type-5 vector-based Ebola vaccine in healthy adults in Sierra Leone: a single-centre, randomised, double-blind, placebo-controlled, phase 2 trial

Feng-Cai Zhu, MSc†, Alie H Wurie, MSc†, Li-Hua Hou, PhD, Qi Liang, BS, Yu-Hua Li, PhD, James B W Russell, MD, Shi-Po Wu, PhD, Jing-Xin Li, PhD, Yue-Mei Hu, BS, Qiang Guo, PhD, Wen-Bo Xu, MD, Abdul R Wurie, MD, Wen-Juan Wang, MSc, Zhe Zhang, BS, Wen-Jiao Yin, MD, Manal Ghazzawi, BS, Xu Zhang, BS, Lei Duan, MSc, Dr Jun-Zhi Wang, PhD, Dr Wei Chen

Background
A recombinant adenovirus type-5 vector-based vaccine expressing the glycoprotein of Ebola Zaire Makona variant showed good safety and immunogenicity in a phase 1 trial of healthy Chinese adults. We aimed to assess the safety and immunogenicity of this vaccine in healthy adults in Sierra Leone and to determine the optimal dose.

Methods
We did a single-centre, randomised, double-blind, placebo-controlled, phase 2 clinical trial at Sierra Leone–China Friendship Hospital, Freetown, Sierra Leone. We recruited healthy adults aged 18–50 years who were HIV negative, had no history of Ebola virus infection, and had no previous immunisation with other Ebola vaccine candidates. Participants were sequentially enrolled and randomly assigned (2:1:1), by computer-generated block randomisation (block size of eight), to receive the high-dose vaccine (1·6 × 1011 viral particles), low-dose vaccine (8·0 × 1010 viral particles), or placebo (containing only vaccine excipients, with no viral particles). Participants, investigators, and study staff (except two study pharmacists) were masked from treatment allocation. The primary safety outcome was occurrence of solicited adverse reactions within 7 days of vaccination, analysed by intention to treat. The primary immunogenicity outcome was glycoprotein-specific antibody responses at days 14, 28, and 168 after vaccination, analysed in all vaccinated participants who had blood samples drawn for antibody tests. The trial is registered with the Pan African Clinical Trials Registry, number PACTR201509001259869, and is completed.

Findings
During Oct 10–28, 2015, 500 participants were enrolled and randomly assigned to receive the high-dose vaccine (n=250), low-dose vaccine (n=125), or placebo (n=125). 132 (53%) participants in the high-dose group, 60 (48%) in the low-dose group, and 54 (43%) in the placebo group reported at least one solicited adverse reaction within 7 days of vaccination. Most adverse reactions were mild and self-limiting. Solicited injection-site adverse reactions were significantly more frequent in vaccine recipients (65 [26%] in high-dose group and 31 [25%] in low-dose group) than in those receiving placebo (17 [14%]; p=0·0169). Glycoprotein-specific antibody responses were detected from day 14 onwards (geometric mean titre 1251·0 [95% CI 976·6–1602·5] in low-dose group and 1728·4 [1459·4–2047·0] in high-dose group) and peaked at day 28 (1471·8 [1151·0–1881·8] and 2043·1 [1762·4–2368·4]), but declined quickly in the following months (223·3 [148·2–336·4] and 254·2 [185·0–349·5] at day 168). Geometric mean titres in the placebo group remained around 6·0–6·8 throughout the study period. Three serious adverse events (malaria, gastroenteritis, and one fatal asthma episode) were reported in the high-dose vaccine group, but none was deemed related to the vaccine.

Interpretation
The recombinant adenovirus type-5 vector-based Ebola vaccine was safe and highly immunogenic in healthy Sierra Leonean adults, and 8·0 × 1010 viral particles was the optimal dose.

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)32617-4/fulltext