Diallo Mamadou Saliou Kalifa, Ayouba Ahidjo, Keita Alpha Kabinet, Thaurignac Guillaume, Sow Mamadou Saliou, Kpamou Cécé, Barry Thierno Alimou, Msellati Philippe, Etard Jean-François, Peeters Martine, Ecochard René, Delaporte Eric, Toure Abdoulaye
Université de Montpellier-Institut de Recherche pour le Développement-Institut National de la Santé et de la Recherche Médicale, Montpellier, France; Centre de Recherche et de Formation en Infectiologie de Guinée, Université Gamal Abdel Nasser de Conakry, Conakry, Guinea.
Université de Montpellier-Institut de Recherche pour le Développement-Institut National de la Santé et de la Recherche Médicale, Montpellier, France.
Lancet Microbe. 2021 Dec;2(12):e676-e684. doi: 10.1016/S2666-5247(21)00170-1. Epub 2021 Sep 3.
Insufficient long-term data are available on antibody kinetics in survivors of Ebola virus disease (EVD). Likewise, few studies, with very small sample sizes, have investigated cross-reactions between Ebolavirus spp. In this study, we aimed to assess the humoral antibody response and its determinants in survivors of EVD and assess cross-reactivity of antibodies between diverse Ebolavirus spp.
In this observational, prospective cohort study, we collected blood samples from patients from three recruitment sites in Guinea included in the Postebogui study, and we assessed IgG antibody binding to recombinant glycoprotein, nucleoprotein, and 40-kDa viral protein (VP40) of Zaire (EBOV), Bundibugyo (BDBV), and Sudan (SUDV) Ebolaviruses. Participants from the PostEbogui study, from whom we had at least one blood sample that could be tested for the presence of antibodies, were eligible for this analysis. Patients in the PostEbogui study were assessed clinically at inclusion, 1 month and 3 months later, and subsequently every 6 months for up to 60 months after discharge from the Ebola treatment centre. We explored predictors of glycoprotein, nucleoprotein, and VP40 antibody concentrations through a linear mixed model. A logistic mixed model was done to estimate the probability of seropositivity and associated determinants. We assessed cross-reactivity by use of hierarchical cluster analysis.
Of the 802 patients included in the Postebogui study, 687 were included in our analyses. 310 (45%) patients were men and 377 (55%) were women, with an overall median age at the time of the first blood sample of 27·3 years (IQR 19·5-38·2). We observed an overall significant decrease over time of EBOV antibodies, with antibodies against nucleoproteins decreasing more rapidly. At 60 months after discharge from the Ebola treatment centre, the probability of having antibodies against glycoproteins was 76·2% (95% CI 67·2-83·3), against nucleoproteins was 59·4% (46·3-71·3), and against VP40 was 60·9% (51·4-69·8). Persistence of EBOV RNA in semen was associated with higher concentrations of IgG antibodies against nucleoprotein EBOV antigens. Individually, we observed in some survivors an antibody wax-and-wane pattern. The proportion of cross-reactions was highest between glycoproteins from Kissidougou and Mayinga EBOV strains (94·5%, 95% CI 92·5-96·1), followed by EBOV VP40 and BDBV VP40 (88·3%, 85·7-90·6), and EBOV VP40 and SUDV VP40 (83·3%, 80·3-86·1).
The probability for survivors of EVD to have antibodies against one or more EBOV antigens remained high, although approximately 25% of survivors had undetectable antibodies, which could have implications, such as a possible decreasing population immunity, for future Ebola outbreaks in the same region.
Reacting-Institut National de la Santé et de la Recherche Médicale, Institut de Recherche pour le Developpement, and Montpellier Université d'Excellence.
关于埃博拉病毒病（EVD）幸存者抗体动力学的长期数据不足。同样，很少有研究（样本量非常小）调查埃博拉病毒属之间的交叉反应。在本研究中，我们旨在评估EVD幸存者的体液抗体反应及其决定因素，并评估不同埃博拉病毒属之间抗体的交叉反应性。
在这项观察性前瞻性队列研究中，我们从几内亚三个招募地点纳入Postebogui研究的患者中采集血样，并评估IgG抗体与扎伊尔（EBOV）、本迪布焦（BDBV）和苏丹（SUDV）埃博拉病毒的重组糖蛋白、核蛋白和40 kDa病毒蛋白（VP40）的结合情况。Postebogui研究中至少有一份血样可检测抗体存在的参与者符合本分析的条件。Postebogui研究中的患者在纳入时、1个月和3个月后进行临床评估，随后在从埃博拉治疗中心出院后的60个月内每6个月评估一次。我们通过线性混合模型探索糖蛋白、核蛋白和VP40抗体浓度的预测因素。采用逻辑混合模型估计血清阳性概率及相关决定因素。我们使用层次聚类分析评估交叉反应性。
在Postebogui研究纳入的802例患者中，687例纳入我们的分析。310例（45%）为男性，377例（55%）为女性，首次采血时的总体中位年龄为27.3岁（IQR 19.5 - 38.2）。我们观察到EBOV抗体随时间总体显著下降，其中针对核蛋白的抗体下降更快。在从埃博拉治疗中心出院60个月时，针对糖蛋白的抗体阳性概率为76.2%（95%CI 67.2 - 83.3），针对核蛋白的为59.4%（46.3 - 71.3），针对VP40的为60.9%（51.4 - 69.8）。精液中EBOV RNA的持续存在与针对核蛋白EBOV抗原的IgG抗体浓度较高有关。我们在一些幸存者中单独观察到抗体的波动模式。交叉反应比例最高的是基西杜古和马伊inga EBOV株的糖蛋白之间（94.5%，95%CI 92.5 - 96.1），其次是EBOV VP40和BDBV VP40之间（88.3%，85.7 - 90.6），以及EBOV VP40和SUDV VP40之间（83.3%，80.3 - 86.1）。
EVD幸存者针对一种或多种EBOV抗原产生抗体的概率仍然很高，尽管约25%的幸存者抗体检测不到，这可能对同一地区未来的埃博拉疫情产生影响，如可能导致群体免疫力下降。
Reacting - 法国国家卫生与医学研究所以及发展研究所、蒙彼利埃卓越大学。
