title: Safety and immunogenicity of a novel recombinant adenovirus type-5 vector-based Ebola vaccine in healthy adults in China: preliminary report of a randomised, double-blind, placebo-controlled, phase 1 trial.
abstract: BACKGROUND
  Up to now, all tested Ebola virus vaccines have been based on the virus strain from the Zaire outbreak in 1976. We aimed to assess the safety and immunogenicity of a novel recombinant adenovirus type-5 vector-based Ebola vaccine expressing the glycoprotein of the 2014 epidemic strain.
  
  
  METHODS
  We did this randomised, double-blind, placebo-controlled, phase 1 clinical trial at one site in Taizhou County, Jiangsu Province, China. Healthy adults (aged 18-60 years) were sequentially enrolled and randomly assigned (2:1), by computer-generated block randomisation (block size of six), to receive placebo, low-dose adenovirus type-5 vector-based Ebola vaccine, or high-dose vaccine. Randomisation was pre-stratified by dose group. All participants, investigators, and laboratory staff were masked to treatment allocation. The primary safety endpoint was occurrence of solicited adverse reactions within 7 days of vaccination. The primary immunogenicity endpoints were glycoprotein-specific antibody titres and T-cell responses at day 28 after the vaccination. Analysis was by intention to treat. The study is registered with ClinicalTrials.gov, number NCT02326194.
  
  
  RESULTS
  Between Dec 28, 2014, and Jan 9, 2015, 120 participants were enrolled and randomly assigned to receive placebo (n=40), low-dose vaccine (n=40), or high-dose vaccine. Participants were followed up for 28 days. Overall, 82 (68%) participants reported at least one solicited adverse reaction within 7 days of vaccination (n=19 in the placebo group vs n=27 in the low-dose group vs n=36 in the high-dose group; p=0·0002). The most common reaction was mild pain at the injection site, which was reported in eight (20%) participants in the placebo group, 14 (35%) participants in the low-dose group, and 29 (73%) participants in the high-dose vaccine group (p<0·0001). We recorded no statistical differences in other adverse reactions and laboratory tests across groups. Glycoprotein-specific antibody titres were significantly increased in participants in the low-dose and high-dose vaccine groups at both day 14 (geometric mean titre 421·4 [95% CI 249·7-711·3] and 820·5 [598·9-1124·0], respectively; p<0·0001) and day 28 (682·7 [424·3-1098·5] and 1305·7 [970·1-1757·2], respectively; p<0·0001). T-cell responses peaked at day 14 at a median of 465·0 spot-forming cells (IQR 180·0-1202·5) in participants in the low-dose group and 765·0 cells (400·0-1460·0) in those in the high-dose group. 21 (18%) participants had mild fever (n=9 in the placebo group, n=6 in the low-dose group, and n=6 in the high-dose group). No serious adverse events were recorded.
  
  
  CONCLUSIONS
  Our findings show that the high-dose vaccine is safe and robustly immunogenic. One shot of the high-dose vaccine could mount glycoprotein-specific humoral and T-cell response against Ebola virus in 14 days.
  
  
  BACKGROUND
  China National Science and Technology, Beijing Institute of Biotechnology, and Tianjin CanSino Biotechnology.
authors: Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu Province, China.
authors: Feng-Cai
authors: FC
authors: Zhu
authors: Beijing Institute of Biotechnology, Beijing, China.
authors: Li-Hua
authors: LH
authors: Hou
authors: Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu Province, China.
authors: Jing-Xin
authors: JX
authors: Li
authors: Beijing Institute of Biotechnology, Beijing, China.
authors: Shi-Po
authors: SP
authors: Wu
authors: Department of Public Health, Southeast University, Nanjing, Jiangsu Province, China.
authors: Pei
authors: P
authors: Liu
authors: Beijing Institute for Drug and Instrument Quality Control, Beijing, China.
authors: Gui-Rong
authors: GR
authors: Zhang
authors: Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu Province, China.
authors: Yue-Mei
authors: YM
authors: Hu
authors: Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu Province, China.
authors: Fan-Yue
authors: FY
authors: Meng
authors: Beijing Institute of Biotechnology, Beijing, China.
authors: Jun-Jie
authors: JJ
authors: Xu
authors: Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu Province, China.
authors: Rong
authors: R
authors: Tang
authors: Beijing Institute of Biotechnology, Beijing, China.
authors: Jin-Long
authors: JL
authors: Zhang
authors: Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu Province, China.
authors: Wen-Juan
authors: WJ
authors: Wang
authors: Tianjin CanSino Biotechnology Inc, Tianjin, China.
authors: Lei
authors: L
authors: Duan
authors: Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu Province, China.
authors: Kai
authors: K
authors: Chu
authors: Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu Province, China.
authors: Qi
authors: Q
authors: Liang
authors: Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu Province, China.
authors: Jia-Lei
authors: JL
authors: Hu
authors: Department of Public Health, Southeast University, Nanjing, Jiangsu Province, China.
authors: Li
authors: L
authors: Luo
authors: Tianjin CanSino Biotechnology Inc, Tianjin, China.
authors: Tao
authors: T
authors: Zhu
authors: National Institute for Food and Drug Control, Beijing, China.
authors: Jun-Zhi
authors: JZ
authors: Wang
authors: Beijing Institute of Biotechnology, Beijing, China. Electronic address: cw0226@foxmail.com.
authors: Wei
authors: W
authors: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D017321:Clinical Trials, Phase I as Topic; D046129:Ebola Vaccines / Q000008:administration & dosage / Q000276:immunology; D029043:Ebolavirus / Q000276:immunology; D005260:Female; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D055261:Immunogenetic Phenomena; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D055815:Young Adult
chemical_list: D046129:Ebola Vaccines; D006023:Glycoproteins