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. 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 (). 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 90 [28%] of 317 group 2 participants) and headache (91 [29%] 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]). 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. Innovative Medicines Initiative 2 Joint Undertaking and Coalition for Epidemic Preparedness Innovations.

中文翻译：

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Ad26.ZEBOV、MVA-BN-Filo 埃博拉病毒病疫苗方案加 Ad26.ZEBOV 加强剂在刚果民主共和国医疗保健和一线工作人员中的 1 年与 2 年对比：开放式研究的次要和探索性结果标签、随机、2 期试验


卫生保健提供者和一线工作人员在埃博拉病毒爆发期间面临感染埃博拉病毒病的风险，从而成为该疾病的驱动因素。我们的目的是评估 Ad26.ZEBOV、MVA-BN-Filo 疫苗方案的长期免疫原性，以及首次接种后 1 年或 2 年时 Ad26.ZEBOV 加强疫苗接种的安全性和免疫记忆反应。 - 危险人群。这项开放标签、单中心、随机、2 期试验在刚果民主共和国博恩代一家医院内的一个研究中心进行。成人卫生保健提供者和一线工作人员（不包括已知的埃博拉病毒病史者）通过三角肌肌内注射 0·5 mL 肌肉注射，每隔 56 天接种两剂异源疫苗，包含Ad26.ZEBOV作为第一剂量和MVA-BN-Filo作为第二剂量。在第一天初次接种疫苗后，参与者通过按顺序打开的随机信封被随机分配 (1:1)，以便在接种后 1 年（第 1 组）或 2 年（第 2 组）接受 Ad26.ZEBOV 加强疫苗接种第一剂。我们提出了该试验的次要和探索性目标——主要目标的结果已在其他地方发表。我们使用丝状病毒动物非临床组 ELISA 测量了每组六个时间点的免疫原性，作为埃博拉病毒糖蛋白特异性 IgG 结合抗体的几何平均浓度 (GMC)。我们评估了最后一次接种后 6 个月内发生的严重不良事件，以及加强疫苗接种后 7 天内报告的局部和全身主动和主动不良事件。 根据方案分析抗体反应，根据完整分析集 (FAS) 分析严重不良事件，并分析所有强化 FAS 参与者的不良事件。该试验已于 () 完成注册。 2019年12月18日至2020年2月8日期间，招募了699名医疗保健提供者和一线工作人员，其中698人被随机分配（350人分配到第1组，348人分配到第2组[FAS]）； 534 名 (77%) 参与者为男性，164 名 (23%) 为女性。第 1 组中的 319 名患者和第 2 组中的 317 名患者接受了加强接种。第 1 组中的 29 名（8%）和第 2 组中的 26 名（7%）没有完成研究，主要是由于失访或搬出研究区域。在两组中，注射部位疼痛或压痛（319 名第 1 组参与者中的 87 名 [27%]，317 名第 2 组参与者中的 90 [28%]）和头痛（91 [29%] 93 [29%]）是最常见的引发与研究产品相关的不良事件。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（发烧≥40·0°C）。在加强疫苗接种前，314 名第 1 组参与者（首次接种后 1 年）和 274 名参与者中，埃博拉病毒糖蛋白特异性 IgG 结合抗体 GMC 为 279·9 ELISA 单位 (EU)/mL (95% CI 250·6–312·7)。 ·6 EU/mL (242·1–311·5)，310 名第 2 组参与者（首次给药后 2 年）。与第 1 天接种疫苗前相比，第 1 组的这些值高出 5·2 倍，第 2 组的这些值高出 4·9 倍。加强接种后 7 天，这些值增加至 10 781·6 EU/mL (9354·4–12第 1 组为 426·4)，第 2 组为 10 746·9 EU/mL (9208·7–12 542·0)，两组均比加强免疫前高约 39 倍。 299 名第 1 组参与者在加强接种后 1 年，仍观察到 GMC 比加强接种前高 7·6 倍 (2133·1 EU/mL [1827·7–2489·7])。 总体而言，疫苗方案和加强剂量的耐受性良好。在第一次接种后 1 年和 2 年加强的参与者中观察到类似且强大的体液免疫反应，支持在高危人群中预防性疫苗接种的方案的使用和加强剂量管理的灵活性。创新药物倡议 2 流行病防范创新联合行动和联盟。