Longitudinal antibody and T cell responses in Ebola virus disease survivors and contacts: an observational cohort study

Abstract

Background The 2013-16 Ebola virus disease epidemic in west Africa caused international alarm due to its rapid and extensive spread resulting in a significant death toll and social unrest within the affected region. The large number of cases provided an opportunity to study the long-term kinetics of Zaire ebolavirus-specific immune response of survivors in addition to known contacts of those infected with the virus.Methods In this observational cohort study, we worked with leaders of Ebola virus disease survivor associations in two regions of Guinea, Guéckédou and Coyah, to recruit survivors of Ebola virus disease, contacts from households of individuals known to have had Ebola virus disease, and individuals who were not knowingly associated with infected individuals or had not had Ebola virus disease symptoms to serve as negative controls. We did Zaire ebolavirus glycoprotein-specific T cell analysis on peripheral blood mononuclear cells (PBMCs) on location in Guinea and transported plasma and PBMCs back to Europe for antibody quantification by ELISA, functional neutralising antibody analysis using live Zaire ebolavirus, and T cell phenotype studies. We report on the longitudinal cellular and humoral response among Ebola virus disease survivors and highlight potentially paucisymptomatic infection.Findings We recruited 117 survivors of Ebola virus disease, 66 contacts, and 23 negative controls. The mean neutralising antibody titre among the Ebola virus disease survivors 3-14 months after infection was 1/174 (95% CI 1/136-1/223). Individual results varied greatly from 1/10 to more than 1/1000 but were on average ten times greater than that induced after 1 month by single dose Ebola virus vaccines. Following reactivation with glycoprotein peptide, the mean T cell responses among 116 Ebola virus disease survivors as measured by ELISpot was 305 spot-forming units (95% CI 257-353). The dominant CD8+ polyfunctional T cell phenotype, as measured among 53 Ebola virus disease survivors, was interferon γ+, tumour necrosis factor+, interleukin-2-, and the mean response was 0•046% of total CD8+ T cells (95% CI 0•021-0•071). Additionally, both neutralising antibody and T cell responses were detected in six (9%) of 66 Ebola virus disease contacts. We also noted that four (3%) of 117 individuals with Ebola virus disease infections did not have circulating Ebola virus-specific antibodies 3 months after infection.Interpretation The continuous high titre of neutralising antibodies and increased T cell response might support the concept of long-term protective immunity in survivors. The existence of antibody and T cell responses in contacts of individuals with Ebola virus disease adds further evidence to the existence of sub-clinical Ebola virus infection.

Associations Between Antibody Fc-Mediated Effector Functions and Long-Term Sequelae in Ebola Virus Survivors

“…A surprising finding of this study is that a minority of household contacts also had polyfunctional antibody effector functions. Polyfunctional responses were more frequent in the contacts that presented two or more symptoms at the time of the outbreak, indicating that some of them might have a milder or subclinical form of the disease, as suggested by other studies (33)(34)(35). Alternatively, it has also been documented that EBOV seropositivity in parts of Africa, including Uganda, is associated with wild animals contacts (35)(36)(37), and thus this baseline seropositivity may also contribute to the Fc-mediated antibody effector response that we observed in some household contacts.…”

Distinct transcriptional responses to fatal Ebola virus infection in cynomolgus and rhesus macaques suggest species-specific immune responses

“…Both B cell-and T cell-mediated responses are believed to be correlates of protection against EBOV infection, as indicated by high levels of neutralizing antibodies and antiviral T cells in human EVD survivors [2,14,15,46,47]. On the other hand, lymphopenia is a characteristic of EVD [16,[19][20][21].…”

“…In contrast, infection of DCs results in reduced expression of costimulatory molecules and impaired antigen presentation which in turn disrupts the mobilization of adaptive immunity [10][11][12][13]. This includes T cell-mediated and humoral immunity, both which are critical for controlling infection and conferring vaccine-mediated protection [2,14,15]. Fatal EVD cases are associated with a robust and sustained adaptive systemic cytokine storm and dramatic loss of lymphocytes, while survivors show early control of innate and immune responses [16][17][18][19][20][21].…”

SARS-CoV-2 Cellular Infection and Therapeutic Opportunities: Lessons Learned from Ebola Virus

“…Furthermore, as already discussed, the passive infusion of neutralizing antibodies has shown efficacy in the treatment of EVD [ 99 ], reinforcing the importance of eliciting this sort of antibodies by vaccination ( Figure 2 ). Accordingly, previous results obtained with EBOV survivors showed that these individuals developed a strong neutralizing humoral response to EBOV GP [ 142 ] that can be higher than the humoral response observed in deceased patients [ 143 , 144 ].…”