Nyombayire Julien, Ingabire Rosine, Mazzei Amelia, Sharkey Tyronza, Umuhoza Claudine, Mukamuyango Jeannine, Allen Susan, Tichacek Amanda, Parker Rachel, Wall Kristin M, Katwere Michael, Keshinro Babajide, Gaddah Auguste, Wang Yan, Forcheh Chiara A, McLean Chelsea, Oriol-Mathieu Valérie, Luhn Kerstin, Robinson Cynthia, Karita Etienne
Rwanda Zambia Health Research Group, Center for Family Health Research/Project San Francisco, Kigali, Rwanda.
Rwanda Zambia Health Research Group, Department of Pathology & Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA, USA.
Nat Med. 2025 Sep 8. doi: 10.1038/s41591-025-03932-z.
Risk of death for both mother and fetus following Ebola virus infection is extremely high. In this study, healthy women in Rwanda aged ≥18 years were randomized to two-dose Ebola vaccination (Ad26.ZEBOV, MVA-BN-Filo) during pregnancy (group A) or postpartum (group B). Unvaccinated pregnant group B women served as control. This was a parallel, randomized, controlled, open-label, single-center trial to evaluate the safety (primary endpoint-outcomes of interest and serious adverse events (SAEs)) and immunogenicity (secondary endpoint) of the two-dose Ebola vaccination. Among 3,484 women screened, 2,013 were randomized, and 2,012 women and 1,945 infants born alive were descriptively analyzed. Adverse outcomes of interest occurred in women (5.2% in group A and 7.3% in group B) and infants (26.0% in group A and 25.6% in group B). The most common maternal outcome of interest was pathways to preterm birth (3.2% in group A and 3.4% in group B), and the most common infant outcome of interest was small for gestational age (14.3% in group A and 11.8% in group B). Maternal/fetal and neonatal/infant SAE frequencies were comparable between groups (9.8% in group A, 9.0% in group B and 21.9% in group A, 15.9% in group B, respectively). Anti-Ebola virus glycoprotein-specific binding antibody response (secondary endpoint) was sustained in ≥90% of women at 1 year postdose 1. In group A, binding antibodies were detected in cord blood (99%) and infant serum (95%) samples 14 weeks postbirth. The trial met all primary and secondary objectives. Ad26.ZEBOV, MVA-BN-Filo did not raise concerns regarding adverse maternal/fetal or neonatal/infant outcomes, had no unexpected safety issues, and induced binding antibody responses in women and offspring through passive transfer. ClinicalTrials.gov registration: NCT04556526 .
埃博拉病毒感染后母亲和胎儿的死亡风险极高。在本研究中，卢旺达年龄≥18岁的健康女性被随机分为两组，一组在孕期接受两剂埃博拉疫苗接种（Ad26.ZEBOV，MVA-BN-Filo）（A组），另一组在产后接种（B组）。未接种疫苗的B组孕妇作为对照。这是一项平行、随机、对照、开放标签、单中心试验，旨在评估两剂埃博拉疫苗接种的安全性（主要终点——感兴趣的结局和严重不良事件（SAE））和免疫原性（次要终点）。在3484名接受筛查的女性中，2013名被随机分组，对2012名女性和1945名活产婴儿进行了描述性分析。感兴趣的不良结局在女性中发生的比例为（A组5.2%，B组7.3%），在婴儿中发生的比例为（A组26.0%，B组25.6%）。最常见的母亲感兴趣的结局是早产途径（A组3.2%，B组3.4%），最常见的婴儿感兴趣的结局是小于胎龄（A组14.3%，B组11.8%）。两组间母亲/胎儿和新生儿/婴儿严重不良事件的发生率相当（A组9.8%，B组9.0%；A组21.9%，B组15.9%）。在第1剂接种后1年，≥90%的女性维持了抗埃博拉病毒糖蛋白特异性结合抗体反应（次要终点）。在A组中，出生后14周时，脐带血样本（99%）和婴儿血清样本（95%）中检测到结合抗体。该试验达到了所有主要和次要目标。Ad26.ZEBOV，MVA-BN-Filo未引发对母亲/胎儿或新生儿/婴儿不良结局的担忧，没有意外的安全问题，并且通过被动转移在女性及其后代中诱导了结合抗体反应。ClinicalTrials.gov注册号：NCT04556526 。
