Summary 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. Findings 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. Interpretation 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. Funding China National Science and Technology, Beijing Institute of Biotechnology, and Tianjin CanSino Biotechnology.
Summary Background 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. Methods 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 × 1010 viral particles, 1·6 × 1011 viral 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. Findings 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 × 1010 viral particles (low dose, n=40), Ebola vaccine at 1·6 × 1011 viral particles (high dose, n=40), or placebo (n=40, in two groups of 20). After prime vaccination, the geometric mean titer (GMT) of ELISA EC90 peaked 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 EC90 titres 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. Interpretation The adenovirus 5-vectored Ebola vaccine of 1·6 × 1011 viral particles was highly immunogenic and safe. The lower dose of 4·0 × 1010 viral 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. Funding Chinese Ministry of Science and Technology and The National Health and Family Planning Commission, Beijing Institute of Biotechnology, and Tianjin CanSino Biotechnology.
Screening for atrial fibrillation before onset of symptoms and the subsequent initiation of oral anticoagulants could prevent stroke and death. The most cost-effective strategy to screen for atrial ...fibrillation in a population at high risk aged 65 years and older is unknown. Therefore, we aimed to investigate whether more frequent electrocardiography (ECG) recordings would significantly improve the detection of atrial fibrillation compared with annual ECG screenings.
We did a randomised controlled trial that compared different screening frequencies of 30 s single-lead ECG (AliveCor Heart Monitor) in the detection of atrial fibrillation in Chinese residents (≥65 years) in five community health centres in Shanghai, China. Only participants without history of atrial fibrillation and without atrial fibrillation rhythm at baseline were eligible for inclusion in the trial. Random assignment was done with the use of a random number table and stratified for study site. Participants were randomly assigned in a 1:1 ratio to annual or quarterly screening groups. The quarterly screening group was further randomly assigned in a 3:1 ratio to subgroups of quarterly screening and quarterly screening plus (which involved ECG screening once per week for the first month of follow-up, then quarterly for the remainder of follow-up). The primary outcome was the detection rate of atrial fibrillation. The intention-to-treat analysis was done for all randomly assigned patients who had at least one ECG recording during follow-up. This trial was registered at ClinicalTrials.gov, NCT02990741, and terminated on Oct 31, 2020.
Between April 17, 2017, and June 26, 2018, 8240 participants were randomly assigned to annual screening (n=4120), quarterly screening (n=3090), and quarterly screening plus (n=1030), with a mean number of ECG recordings of 1·6 (SD 0·5) for annual screening, 3·5 (1·5) for quarterly screening, and 5·2 (2·9) for quarterly screening plus during a median of 2·1 years follow-up (13 284 person-years). 73 incident cases of atrial fibrillation occurred: 26 in the annual screening group (4·1 per 1000 person-years) and 47 in the quarterly screening group (6·7 per 1000 person-years. Quarterly screening was associated with a significant increase in the detection rate of atrial fibrillation, compared with annual screening (hazard ratio HR 1·71; 95% CI 1·06–2·76; p=0·029). 40 incident cases were detected in quarterly screening (7·2 per 1000 person-years; HR compared to annual screening, 1·83; 95% CI 1·12–3·00; p=0·017) and seven in the quarterly screening plus group (4·8 per 1000 person-years; HR compared with annual screening, 1·24; 0·54–2·86; p=0·61). No significant difference was noted between quarterly screening and the quarterly screening plus group (HR of quarterly screening plus compared with quarterly screening, 0·68; 0·30–1·52; p=0·35).
Quarterly 30 s single-lead ECG screening was associated with a significantly higher detection rate of incident atrial fibrillation compared with annual screening, but additional once per week screenings in the first month did not yield an added predictive value. Quarterly screening might be considered in a general population at a high risk of atrial fibrillation, such as those aged 65 years and older.
Bayer Healthcare Company.
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