Background

Questions remain concerning the rapidity of immune responses and the durability and safety of vaccines used to prevent Zaire Ebola virus disease.

Methods

We conducted two randomized, placebo-controlled trials — one involving adults and one involving children — to evaluate the safety and immune responses of three vaccine regimens against Zaire Ebola virus disease: Ad26.ZEBOV followed by MVA-BN-Filo 56 days later (the Ad26–MVA group), rVSVΔG-ZEBOV-GP followed by placebo 56 days later (the rVSV group), and rVSVΔG-ZEBOV-GP followed by rVSVΔG-ZEBOV-GP 56 days later (the rVSV–booster group). The primary end point was antibody response at 12 months, defined as having both a 12-month antibody concentration of at least 200 enzyme-linked immunosorbent assay units (EU) per milliliter and an increase from baseline in the antibody concentration by at least a factor of 4.

Results

A total of 1400 adults and 1401 children underwent randomization. Among both adults and children, the incidence of injection-site reactions and symptoms (e.g., feverishness and headache) was higher in the week after receipt of the primary and second or booster vaccinations than after receipt of placebo but not at later time points. These events were largely low-grade. At month 12, a total of 41% of adults (titer, 401 EU per milliliter) and 78% of children (titer, 828 EU per milliliter) had a response in the Ad26–MVA group; 76% (titer, 992 EU per milliliter) and 87% (titer, 1415 EU per milliliter), respectively, had a response in the rVSV group; 81% (titer, 1037 EU per milliliter) and 93% (titer, 1745 EU per milliliter), respectively, had a response in the rVSV–booster group; and 3% (titer, 93 EU per milliliter) and 4% (titer, 67 EU per milliliter), respectively, had a response in the placebo group (P<0.001 for all comparisons of vaccine with placebo). In both adults and children, antibody responses with vaccine differed from those with placebo beginning on day 14.

Conclusions

No safety concerns were identified in this trial. With all three vaccine regimens, immune responses were seen from day 14 through month 12. (Funded by the National Institutes of Health and others; PREVAC ClinicalTrials.gov number, NCT02876328; EudraCT numbers, 2017-001798-18 and 2017-001798-18/3rd; and Pan African Clinical Trials Registry number, PACTR201712002760250.)

中文翻译：

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扎伊尔埃博拉病毒病疫苗的随机试验

背景

关于免疫反应的速度以及用于预防扎伊尔埃博拉病毒病的疫苗的耐用性和安全性的问题仍然存在。

方法

我们进行了两项随机、安慰剂对照试验——一项涉及成人，另一项涉及儿童——以评估三种针对扎伊尔埃博拉病毒病疫苗方案的安全性和免疫反应：Ad26.ZEBOV，56 天后接种 MVA-BN-Filo（ Ad26–MVA 组）、rVSVΔG-ZEBOV-GP 56 天后服用安慰剂（rVSV 组），rVSVΔG-ZEBOV-GP 56 天后服用 rVSVΔG-ZEBOV-GP（rVSV 加强剂组）。主要终点是 12 个月时的抗体反应，定义为 12 个月抗体浓度至少为每毫升 200 酶联免疫吸附测定单位 (EU)，并且抗体浓度较基线增加至少一个因子4.

结果

共有 1400 名成人和 1401 名儿童接受了随机分组。在成人和儿童中，注射部位反应和症状（如发烧和头痛）的发生率在接受初次和第二次或加强疫苗接种后的一周内高于接受安慰剂后，但在以后的时间点则不然。这些事件大多是低级别的。在第 12 个月，共有 41% 的成人（滴度，每毫升 401 EU）和 78% 的儿童（滴度，每毫升 828 EU）在 Ad26-MVA 组中有反应；rVSV 组分别有 76%（滴度，992 EU/毫升）和 87%（滴度，1415 EU/毫升）有反应；分别有 81%（滴度，1037 EU/毫升）和 93%（滴度，1745 EU/毫升）在 rVSV 加强剂组中有反应；和 3%（滴度，每毫升 93 EU）和 4%（滴度，每毫升 67 EU），分别在安慰剂组有反应（对于疫苗与安慰剂的所有比较，P<0.001）。在成人和儿童中，从第 14 天开始，疫苗抗体反应与安慰剂抗体反应不同。

结论

本试验未发现安全问题。对于所有三种疫苗方案，从第 14 天到第 12 个月都出现了免疫反应。（由美国国立卫生研究院和其他机构资助；PREVAC ClinicalTrials.gov 编号为 NCT02876328；EudraCT 编号为 2017-001798-18 和 2017-001798-18 /3rd；和泛非临床试验登记号，PACTR201712002760250。）