背景:在埃博拉病毒爆发期间,卫生保健提供者和一线工作人员面临感染埃博拉病毒病的风险,并因此成为该疾病的驱动因素。我们旨在评估Ad26的长期免疫原性。ZEBOV,MVA-BN-Filo疫苗方案以及对Ad26的安全性和免疫记忆反应。ZEBOV加强疫苗接种在1年或2年后的第一剂在这个有风险的人群。
方法:这个开放标签,单中心,随机化,2期试验在博恩德一家医院内的一个研究地点进行,刚果民主共和国。成人医疗保健提供者和一线工人,不包括那些已知有埃博拉病毒病史的人,通过在三角肌中进行0·5mL肌内注射,以56天的间隔接种两次剂量的异源方案,包括Ad26。ZEBOV作为第一剂量和MVA-BN-Filo作为第二剂量。在第1天初次接种疫苗后,参与者通过随机信封随机分配(1:1),按顺序打开,获得Ad26第一次给药后1年(第1组)或2年(第2组)的ZEBOV加强疫苗接种。我们介绍了次要和探索性目标,主要目标的试验结果已在其他地方发表。我们在每组六个时间点测量了埃博拉病毒糖蛋白特异性IgG结合抗体的几何平均浓度(GMC),使用丝状病毒动物非临床组ELISA。我们评估了最后一次给药后6个月内发生的严重不良事件,以及在加强疫苗接种后7天内报告的局部和全身征求和非征求的不良事件。根据方案分析抗体反应,每个完整分析集(FAS)的严重不良事件,以及所有加强FAS参与者的不良事件。该试验在ClinicalTrials.gov(NCT04186000)上注册完成。
结果:在2019年12月18日至2020年2月8日之间,招募了699名医疗保健提供者和一线工作人员,并随机分配了698人(第1组350人,第2组348人[FAS]);534名(77%)参与者为男性,164名(23%)为女性。第1组中的319和第2组中的317接受了增强剂。第1组的29(8%)和第2组的26(7%)未完成研究,主要是由于失去随访或移出研究区域。在这两组中,注射部位疼痛或压痛(319名第1组参与者中的87[27%]对317名第2组参与者中的90[28%])和头痛(91[29%]对93[29%])是与研究产品相关的最常见的不良事件.一名参与者(第2组)在加强疫苗接种后出现相关的严重不良事件(发热≥40·0°C)。在加强疫苗接种之前,埃博拉病毒糖蛋白特异性IgG结合抗体GMC在314组1参与者(第一剂量后1年)和274·6EU/mL(242·1-311·5)中分别为279·9ELISA单位(EU)/mL(95%CI250·6-312·7)在310组2参与者(第一剂量后2年)中。与第1天接种前相比,第1组的这些值高5·2倍,第2组的这些值高4·9倍。加强疫苗接种后7天,第1组的这些值增加至10781·6EU/mL(9354·4-12426·4),第2组的这些值增加至10746·9EU/mL(9208·7-12542·0),是两组加强疫苗接种前的约39倍.299组1名参与者在加强疫苗接种后1年,仍观察到比加强疫苗接种前高7·6倍的GMC(2133·1EU/mL[1827·7-2489·7]).
结论:总体而言,疫苗方案和加强剂量耐受性良好.在第一次给药后1年和2年,参与者观察到类似的和强大的体液免疫反应。支持在高危人群中预防性接种疫苗的方案和加强剂量给药的灵活性。
背景:创新药物倡议2联合承诺和联盟防疫创新。
BACKGROUND: Health-care providers and front-line workers are at risk of contracting Ebola virus disease during an Ebola virus outbreak and consequently of becoming drivers of the disease. We aimed to assess the long-term immunogenicity of the Ad26.ZEBOV, MVA-BN-Filo vaccine regimen and the safety of and immune memory response to an Ad26.ZEBOV booster vaccination at 1 year or 2 years after the first dose in this at-risk population.
METHODS: This open-label, single-centre, randomised, phase 2 trial was conducted at one study site within a hospital in Boende, Democratic Republic of the Congo. Adult health-care providers and front-line workers, excluding those with a known history of Ebola virus disease, were vaccinated with a two-dose heterologous regimen administered at a 56-day interval via a 0·5 mL intramuscular injection in the deltoid muscle, comprising Ad26.ZEBOV as the first dose and MVA-BN-Filo as the second dose. After the initial vaccination on day 1, participants were randomly assigned (1:1) via randomisation envelopes, opened in a sequential order, to receive an Ad26.ZEBOV booster vaccination at 1 year (group 1) or 2 years (group 2) after the first dose. We present the secondary and exploratory objectives of the trial-results of the primary objective have been published elsewhere. We measured immunogenicity at six timepoints per group as geometric mean concentrations (GMCs) of Ebola virus glycoprotein-specific IgG binding antibodies, using the Filovirus Animal Non-Clinical Group ELISA. We assessed serious adverse events occurring up to 6 months after the last dose and local and systemic solicited and unsolicited adverse events reported for 7 days after the booster vaccination. Antibody responses were analysed per protocol, serious adverse events per full analysis set (FAS), and adverse events for all boosted FAS participants. This trial is registered as completed on ClinicalTrials.gov (NCT04186000).
RESULTS: Between Dec 18, 2019, and Feb 8, 2020, 699 health-care providers and front-line workers were enrolled and 698 were randomly assigned (350 to group 1 and 348 to group 2 [FAS]); 534 (77%) participants were male and 164 (23%) were female. 319 in group 1 and 317 in group 2 received the booster. 29 (8%) in group 1 and 26 (7%) in group 2 did not complete the study, mostly due to loss to follow-up or moving out of the study area. In both groups, injection-site pain or tenderness (87 [27%] of 319 group 1 participants vs 90 [28%] of 317 group 2 participants) and headache (91 [29%] vs 93 [29%]) were the most common solicited adverse events related to the investigational product. One participant (in group 2) had a related serious adverse event after booster vaccination (fever of ≥40·0°C). Before booster vaccination, Ebola virus glycoprotein-specific IgG binding antibody GMCs were 279·9 ELISA units (EU) per mL (95% CI 250·6-312·7) in 314 group 1 participants (1 year after first dose) and 274·6 EU/mL (242·1-311·5) in 310 group 2 participants (2 years after first dose). These values were 5·2 times higher in group 1 and 4·9 times higher in group 2 than before vaccination on day 1. 7 days after booster vaccination, these values increased to 10 781·6 EU/mL (9354·4-12 426·4) for group 1 and 10 746·9 EU/mL (9208·7-12 542·0) for group 2, which were approximately 39 times higher than before booster vaccination in both groups. 1 year after booster vaccination in 299 group 1 participants, a GMC that was 7·6-times higher than before booster vaccination was still observed (2133·1 EU/mL [1827·7-2489·7]).
CONCLUSIONS: Overall, the vaccine regimen and booster dose were well tolerated. A similar and robust humoral immune response was observed for participants boosted 1 year and 2 years after the first dose, supporting the use of the regimen and flexibility of booster dose administration for prophylactic vaccination in at-risk populations.
BACKGROUND: Innovative Medicines Initiative 2 Joint Undertaking and Coalition for Epidemic Preparedness Innovations.