Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, United States of America.
College of Medicine, University of Lagos, Akoka, Lagos, Nigeria.
PLoS Negl Trop Dis. 2018 May 24;12(5):e0006530. doi: 10.1371/journal.pntd.0006530. eCollection 2018 May.
Ebola virus (EBOV) caused more than 11,000 deaths during the 2013-2016 epidemic in West Africa without approved vaccines or immunotherapeutics. Despite its high lethality in some individuals, EBOV infection can produce little to no symptoms in others. A better understanding of the immune responses in individuals who experienced minimally symptomatic and asymptomatic infection could aid the development of more effective vaccines and antivirals against EBOV and related filoviruses.
METHODOLOGY/PRINCIPLE FINDINGS: Between August and November 2017, blood samples were collected from 19 study participants in Lagos, Nigeria, including 3 Ebola virus disease (EVD) survivors, 10 individuals with documented close contact with symptomatic EVD patients, and 6 control healthcare workers for a cross-sectional serosurvey and T cell analysis. The Lagos samples, as well as archived serum collected from healthy individuals living in surrounding areas of the 1976 Democratic Republic of Congo (DRC) epidemic, were tested for EBOV IgG using commercial enzyme-linked immunosorbent assays (ELISAs) and Western blots. We detected antibodies in 3 out of 3 Lagos survivors and identified 2 seropositive individuals not known to have ever been infected. Of the DRC samples tested, we detected antibodies in 9 out of 71 (12.7%). To characterize the T cell responses in the Lagos samples, we developed an anthrax toxin-based enzyme-linked immunospot (ELISPOT) assay. The seropositive asymptomatic individuals had T cell responses against EBOV nucleoprotein, matrix protein, and glycoprotein 1 that were stronger in magnitude compared to the survivors.
CONCLUSION/SIGNIFICANCE: Our data provide further evidence of EBOV exposure in individuals without EVD-like illness and, for the first time, demonstrate that these individuals have T cell responses that are stronger in magnitude compared to severe cases. These findings suggest that T cell immunity may protect against severe EVD, which has important implications for vaccine development.
在 2013 年至 2016 年西非爆发的埃博拉疫情中,埃博拉病毒(EBOV)导致超过 11000 人死亡,当时没有批准的疫苗或免疫疗法。尽管在某些个体中它具有很高的致死率,但在其他个体中,埃博拉病毒感染可能几乎没有症状。更好地了解在经历轻微症状和无症状感染的个体中的免疫反应,可能有助于开发针对埃博拉病毒和相关丝状病毒的更有效的疫苗和抗病毒药物。
方法/主要发现:在 2017 年 8 月至 11 月期间,从尼日利亚拉各斯的 19 名研究参与者中采集了血液样本,包括 3 名埃博拉病毒病(EVD)幸存者、10 名与有症状的 EVD 患者有密切接触的个体和 6 名对照医护人员,进行了横断面血清学调查和 T 细胞分析。拉各斯的样本以及从刚果民主共和国(DRC)1976 年疫情周围地区的健康个体中收集的存档血清,使用商业酶联免疫吸附测定(ELISA)和 Western blot 检测埃博拉病毒 IgG。我们在 3 名拉各斯幸存者中的 3 名中检测到抗体,并发现了 2 名未知曾感染过的血清阳性个体。在所测试的 DRC 样本中,我们在 71 个样本中的 9 个(12.7%)中检测到抗体。为了描述拉各斯样本中的 T 细胞反应,我们开发了一种炭疽毒素酶联免疫斑点(ELISPOT)测定法。血清阳性的无症状个体对埃博拉病毒核蛋白、基质蛋白和糖蛋白 1 的 T 细胞反应的强度大于幸存者。
结论/意义:我们的数据进一步提供了在没有类似埃博拉病毒病的个体中暴露于埃博拉病毒的证据,并且首次证明这些个体的 T 细胞反应的强度大于严重病例。这些发现表明,T 细胞免疫可能对严重的 EVD 有保护作用,这对疫苗开发具有重要意义。