Temporal evolution of the humoral antibody response after Ebola virus disease in Guinea: a 60-month observational prospective cohort study

Background 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. Methods 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. Findings 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 27middot3 years (IQR 19middot5-38middot2). 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 76middot2% (95% CI 67middot2-83middot3), against nucleoproteins was 59middot4% (46middot3-71middot3), and against VP40 was 60middot9% (51middot4-69middot8). 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 (94middot5%, 95% CI 92middot5-96middot1), followed by EBOV VP40 and BDBV VP40 (88middot3%, 85middot7-90middot6), and EBOV VP40 and SUDV VP40 (83middot3%, 80middot3-86middot1). Interpretation 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. Funding Reacting-Institut National de la Sante et de la Recherche Medicale, Institut de Recherche pour le Developpement, and Montpellier Universite d'Excellence. Copyright (c) 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license.

Automated summary

This study aimed to evaluate the humoral antibody response and cross reactivity of antibodies between different Ebolaviruses in survivors of Ebola virus disease. Results showed a significant decrease in EBOV antibodies over time, with antibodies against nucleoproteins decreasing more rapidly. Some survivors exhibited an antibody wax-and-wane pattern.