National Infection Service, Public Health England, Porton Down, UK.
Institute of Virology, Philipps University of Marburg, Marburg, Germany.
Lancet Infect Dis. 2021 Apr;21(4):507-516. doi: 10.1016/S1473-3099(20)30736-2. Epub 2020 Oct 13.
The 2013-16 Ebola virus disease epidemic in west Africa caused international alarm due to its rapid and extensive spread resulting in a significant death toll and social unrest within the affected region. The large number of cases provided an opportunity to study the long-term kinetics of Zaire ebolavirus-specific immune response of survivors in addition to known contacts of those infected with the virus.
In this observational cohort study, we worked with leaders of Ebola virus disease survivor associations in two regions of Guinea, Guéckédou and Coyah, to recruit survivors of Ebola virus disease, contacts from households of individuals known to have had Ebola virus disease, and individuals who were not knowingly associated with infected individuals or had not had Ebola virus disease symptoms to serve as negative controls. We did Zaire ebolavirus glycoprotein-specific T cell analysis on peripheral blood mononuclear cells (PBMCs) on location in Guinea and transported plasma and PBMCs back to Europe for antibody quantification by ELISA, functional neutralising antibody analysis using live Zaire ebolavirus, and T cell phenotype studies. We report on the longitudinal cellular and humoral response among Ebola virus disease survivors and highlight potentially paucisymptomatic infection.
We recruited 117 survivors of Ebola virus disease, 66 contacts, and 23 negative controls. The mean neutralising antibody titre among the Ebola virus disease survivors 3-14 months after infection was 1/174 (95% CI 1/136-1/223). Individual results varied greatly from 1/10 to more than 1/1000 but were on average ten times greater than that induced after 1 month by single dose Ebola virus vaccines. Following reactivation with glycoprotein peptide, the mean T cell responses among 116 Ebola virus disease survivors as measured by ELISpot was 305 spot-forming units (95% CI 257-353). The dominant CD8+ polyfunctional T cell phenotype, as measured among 53 Ebola virus disease survivors, was interferon γ+, tumour necrosis factor+, interleukin-2-, and the mean response was 0·046% of total CD8+ T cells (95% CI 0·021-0·071). Additionally, both neutralising antibody and T cell responses were detected in six (9%) of 66 Ebola virus disease contacts. We also noted that four (3%) of 117 individuals with Ebola virus disease infections did not have circulating Ebola virus-specific antibodies 3 months after infection.
The continuous high titre of neutralising antibodies and increased T cell response might support the concept of long-term protective immunity in survivors. The existence of antibody and T cell responses in contacts of individuals with Ebola virus disease adds further evidence to the existence of sub-clinical Ebola virus infection.
US Food & Drug Administration, Horizon 2020 EU EVIDENT, Wellcome, UK Department for International Development.
For the French translation of the abstract see Supplementary Materials section.
2013-16 年西非埃博拉病毒病疫情因迅速广泛传播而引起国际关注，导致该地区死亡人数众多，社会动荡不安。大量病例为研究扎伊尔埃博拉病毒特异性免疫反应提供了机会，除了已知的感染病毒的接触者外，还包括幸存者和病毒感染者的家庭接触者。
在这项观察性队列研究中，我们与几内亚两个地区（盖凯杜和科亚）埃博拉病毒病幸存者协会的领导人合作，招募埃博拉病毒病幸存者、已知感染埃博拉病毒病的个人家庭接触者以及未与感染个体有过接触或未出现埃博拉病毒病症状的个体作为阴性对照。我们在几内亚现场对外周血单核细胞（PBMC）进行扎伊尔埃博拉病毒糖蛋白特异性 T 细胞分析，并将血浆和 PBMC 运回欧洲，通过 ELISA 定量抗体、使用活扎伊尔埃博拉病毒进行功能性中和抗体分析以及进行 T 细胞表型研究。我们报告了埃博拉病毒病幸存者的纵向细胞和体液反应，并强调了潜在的症状轻微感染。
我们招募了 117 名埃博拉病毒病幸存者、66 名接触者和 23 名阴性对照。感染后 3-14 个月，埃博拉病毒病幸存者的平均中和抗体滴度为 1/174（95%CI 1/136-1/223）。个体结果差异很大，从 1/10 到超过 1/1000，但平均比单次接种埃博拉病毒疫苗后 1 个月诱导的抗体滴度高 10 倍。用糖蛋白肽再激活后，116 名埃博拉病毒病幸存者中 116 名通过 ELISpot 测量的平均 T 细胞反应为 305 个斑点形成单位（95%CI 257-353）。在 53 名埃博拉病毒病幸存者中测量到的主要 CD8+多效性功能 T 细胞表型为干扰素 γ+、肿瘤坏死因子+、白细胞介素-2-，平均反应为总 CD8+T 细胞的 0.046%（95%CI 0.021-0.071）。此外，在 66 名埃博拉病毒病接触者中，有 6 名（9%）检测到中和抗体和 T 细胞反应。我们还注意到，在 117 名埃博拉病毒病感染者中，有 4 名（3%）在感染后 3 个月没有循环的埃博拉病毒特异性抗体。
持续高滴度的中和抗体和增加的 T 细胞反应可能支持幸存者中存在长期保护性免疫的概念。在埃博拉病毒病接触者中存在抗体和 T 细胞反应进一步证明了亚临床埃博拉病毒感染的存在。
美国食品和药物管理局、欧盟地平线 2020 计划 EVIDENT、惠康基金会、英国国际发展部。
