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

Abstract

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 crossreactivity 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.

Dynamics of Antibodies to Ebolaviruses in an Eidolon helvum Bat Colony in Cameroon

“…Our study showed high antibody rates to glycoproteins form three ebolaviruses that circulate in Africa, suggesting that bats encounter at some stage during their life time, probably at end of juvenile and early adult stage, one of the known ebolaviruses or another ebolavirus that cross-reacts with the antigens used. In humans who recovered from Ebolavirus disease in the outbreak in Guinea with the EBOV species, high rates of cross reactivity with other ebolaviruses, SUDV and BDBV, were observed [ 48 ]. Cross-reactivity was also observed in a study using convalescent sera from experimentally infected bats but false positive reactivity with other pathogens cannot be excluded [ 49 ].…”

RNA Viruses, Pregnancy and Vaccination: Emerging Lessons from COVID-19 and Ebola Virus Disease

“…In this study, IgG levels are found to decrease following recovery, which then show a resurgence over a period of time [ 88 ]. Another 60 month observational prospective cohort study carried out with a larger sample size comprising 802 EVD survivors also evidenced a similar antibody ebb and flow pattern [ 89 ]. This periodic waxing and waning of antibodies observed in EVD, warrants investigation also in the context of COVID-19, since it may indicate sub-clinical de novo antigenic stimulation possibly indicative of viral RNA shed from immunologically privileged sites such as eyes, central nervous system and testes [ 90 ].…”

Pan-ebolavirus serology study of healthcare workers in the Mbandaka Health Region, Democratic Republic of the Congo

“…As such, we could not determine the neutralization capacity of the sera tested in this study. However, studies by Adaken et al and Diallo et al show that levels of binding antibody correlate with neutralization and/or protection from disease [ 43 , 44 ]. Further, we could not test for antibodies against Marburg or Ravn viruses due to a lack of an adequate positive control at the time of testing.…”