title: Immunity duration of a recombinant adenovirus type-5 vector-based Ebola vaccine and a homologous prime-boost immunisation in healthy adults in China: final report of a randomised, double-blind, placebo-controlled, phase 1 trial.
abstract: The 2013-15 Ebola virus disease epidemic in west Africa greatly accelerated the development of Ebola vaccine. We aimed to analyse the immune persistence induced by one shot of an adenovirus type-5 vector-based Ebola virus vaccine up to 6 months and the effect of boosting with a homologous vector in healthy adults in China.
  
  
  
  In a randomised, double-blind, placebo-controlled, phase 1 clinical trial in one site in Jiangsu Province, China, 120 healthy adults aged 18-60 years received an initial dose of intramuscular adenovirus type-5 Ebola virus vaccine of 4·0 × 1010viral particles, 1·6 × 1011viral particles, or placebo, and were followed up to day 168. Participants were subsequently re-recruited to receive a booster dose of the same vaccine or placebo, in the same dose, at month 6. Women who were pregnant, breastfeeding, or planned to become pregnant during the next month were excluded. Randomisation was conducted by computer-generated block randomisation. Randomisation data were unmasked for interim analysis of the data obtained between days 0-28 but not disclosed to participants or site staff. Safety and immunogenicity analysis were done on the intention-to-treat population. We aimed to assess the safety profile of the experimental vaccine and the immunity responses to a single-dose immunisation or a homologous prime-boost regimen. Primary outcomes were Ebola glycoprotein-specific ELISA antibody responses 28 days post-boost and the occurrences of adverse reactions post-boost. The original trial and the extended booster study were registered with ClinicalTrials.gov, numbers NCT02326194 and NCT02533791, respectively.
  
  
  
  Between Dec 28, 2014, and Jan 9, 2015, we enrolled 210 volunteers. 90 participants were not randomised due to not meeting inclusion criteria (61), meeting exclusion criteria (4), or withdrawal of consent (25). 120 people were randomly assigned to receive intramuscular Ebola vaccine at 4·0 × 1010viral particles (low dose, n=40), Ebola vaccine at 1·6 × 1011viral particles (high dose, n=40), or placebo (n=40, in two groups of 20). After prime vaccination, the geometric mean titer (GMT) of ELISA EC90peaked at 682·7 (95% CI 424·3-1098·5) in the low-dose vaccine group and 1305·7 (970·1-1757·2) in the high-dose vaccine group at day 28, and then fell gradually through the next a few months to 575·5 (394·8-838·8) in the high-dose vaccine group and 197·9 (107·9-362·7) in the low-dose vaccine group at day 168. No specific response was recorded in the placebo group with a GMT of 5·0. Of the 120 participants involved in the initial trial, ten participants declined to participate, and 110 were included in the boost immunisation: 38 received the low dose, 35 received the high dose, and 37 received the placebo. At day 28 after boost vaccination, the ELISA EC90titres rapidly rose to 6110 (95% CI 4705-7935) in the low-dose group and to 11825 (8904-15705) in the high dose group. 78 of 110 participants reported at least one solicited adverse reaction within the first 7 days after booster administration. Both of the groups who received vaccine showed significantly higher incidence of mild or moderate solicited adverse reactions than did the placebo group.
  
  
  
  The adenovirus 5-vectored Ebola vaccine of 1·6 × 1011viral particles was highly immunogenic and safe. The lower dose of 4·0 × 1010viral particles was also safe, but immunogenicity seemed to be more vulnerable to the pre-existing immunity of adenovirus 5. A homologous priming-boosting regimen with adenovirus type-5 Ebola vaccine at 6 months interval was able to elicit greater antibody responses with longer duration. These results support an immunisation strategy to implement a booster injection for a more durable protection against Ebola virus disease.
  
  
  
  Chinese Ministry of Science and Technology and The National Health and Family Planning Commission, Beijing Institute of Biotechnology, and Tianjin CanSino Biotechnology.
authors.affiliation: Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, Jiangsu Province, China.
authors.forename: Jing-Xin
authors.initials: JX
authors.lastname: Li
authors.affiliation: Beijing Institute of Biotechnology, Fengtai District, Beijing 100039, China.
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Hou
authors.affiliation: Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, Jiangsu Province, China.
authors.forename: Fan-Yue
authors.initials: FY
authors.lastname: Meng
authors.affiliation: Beijing Institute of Biotechnology, Fengtai District, Beijing 100039, China.
authors.forename: Shi-Po
authors.initials: SP
authors.lastname: Wu
authors.affiliation: Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, Jiangsu Province, China.
authors.forename: Yue-Mei
authors.initials: YM
authors.lastname: Hu
authors.affiliation: Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, Jiangsu Province, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Liang
authors.affiliation: Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, Jiangsu Province, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Chu
authors.affiliation: Beijing Institute of Biotechnology, Fengtai District, Beijing 100039, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Beijing Institute of Biotechnology, Fengtai District, Beijing 100039, China.
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Xu
authors.affiliation: Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, Jiangsu Province, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Tang
authors.affiliation: Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, Jiangsu Province, China.
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: Wang
authors.affiliation: School of Public Health, Southeast University, Nanjing 210009, Jiangsu Province, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Liu
authors.affiliation: Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, Jiangsu Province, China.
authors.forename: Jia-Lei
authors.initials: JL
authors.lastname: Hu
authors.affiliation: School of Public Health, Southeast University, Nanjing 210009, Jiangsu Province, China.
authors.forename: Li
authors.initials: L
authors.lastname: Luo
authors.affiliation: Tianjin CanSino Biotechnology Inc, TEDA West District, Tianjin 300457, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Jiang
authors.affiliation: Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, Jiangsu Province, China. Electronic address: jszfc@vip.sina.com.
authors.forename: Feng-Cai
authors.initials: FC
authors.lastname: Zhu
authors.affiliation: Beijing Institute of Biotechnology, Fengtai District, Beijing 100039, China. Electronic address: cw0226@foxmail.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
mesh_terms: D000256:Adenoviridae; D000328:Adult; D002681:China; D004311:Double-Blind Method; D046129:Ebola Vaccines / Q000276:immunology*; D029043:Ebolavirus / Q000276:immunology*; D005260:Female; D005822:Genetic Vectors; D019142:Hemorrhagic Fever, Ebola / Q000517:prevention & control* / Q000821:virology; D006801:Humans; D007117:Immunization, Secondary; D008297:Male; D008875:Middle Aged; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology*
chemical_list: D046129:Ebola Vaccines; D014614:Vaccines, Synthetic