Temporal evolution of the humoral antibody response after Ebola virus disease in Guinea: a 60-month observational prospective cohort study
Authors: Mamadou Saliou Kalifa Diallo, Ahidjo Ayouba, Alpha Kabinet Keita, Guillaume Thaurignac, Mamadou Saliou Sow, Cécé Kpamou, Thierno Alimou Barry, Philippe Msellati, Jean-François Etard, Martine Peeters, René Ecochard, Eric Delaporte, Abdoulaye Toure, Ahidjo Ayouba, Sylvain Baize, Kaba Bangoura, Alimou Barry, Moumié Barry, Mamoudou Cissé, Mohammed Cissé, Eric Delaporte, Jean-François Delfraissy, Christelle Delmas, Alice Desclaux, Saliou Bella Diallo, Mamadou Safiatou Diallo, Mariama Sadjo Diallo, Cécile Etienne, Jean-François Étard, Ousmane Faye, Ibrahima Fofana, Bruno Granouillac, Suzanne Izard, Djenaba Kassé, Alpha Kabinet Keita, Sakoba Keita, Lamine Koivogui, Cécé Kpamou, Christine Lacarabaratz, Sandrine Leroy, Claire Levy Marchal, Yves Levy, N'Fally Magassouba, Laura March, Vincent Mendiboure, Philippe Msellati, Harissatou Niane, Martine Peeters, Yves-Marie Pers, Hervé Raoul, Sidi Lamine Sacko, Ibrahima Savané, Mamadou Saliou Sow, Bernard Taverne, Abdoulaye Touré, Fodé Amara Traoré, Falaye Traoré, Yamoussa Youla, Yazdan Yazdanpanah
Journal: The Lancet Microbe (2021)

BackgroundInsufficient 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.MethodsIn 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.FindingsOf 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).InterpretationThe 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.FundingReacting–Institut National de la Santé et de la Recherche Médicale, Institut de Recherche pour le Developpement, and Montpellier Université d'Excellence.