Article ; Online: Ebola-Detect: A differential serodiagnostic assay for Ebola virus infections and surveillance in the presence of vaccine-induced antibodies.
2022 Volume 82, Page(s) 104186
Abstract: Background: Ebola virus (EBOV) vaccines containing glycoprotein (GP) provide protection against severe Ebola virus disease (EVD). EBO vaccinations elicit antibodies that are detectable in Ebola serodiagnostic tests, as EBOV GP is a major target antigen. ...
| Abstract | Background: Ebola virus (EBOV) vaccines containing glycoprotein (GP) provide protection against severe Ebola virus disease (EVD). EBO vaccinations elicit antibodies that are detectable in Ebola serodiagnostic tests, as EBOV GP is a major target antigen. This vaccine-induced seropositivity presents issues with early detection of natural EBOV infections, following vaccination and during surveillance, leading to 'uninfected' vaccine trial participants being falsely diagnosed as 'EBOV infected' potentially resulting in long-term social and economic distress. Since mass vaccinations are being employed to curtail the recurrent EBOV epidemics in multiple African countries, it is, therefore, essential to differentiate vaccine-induced from natural infection-induced antibodies by a differential serodiagnosis assay for accurate detection of Ebola virus infections. Methods: To develop a serodiagnostic test that can differentiate between individuals with EBOV infection-induced antibodies and individuals with EBOV vaccine-induced antibodies, we analysed peptides of EBOV viral protein 40 (VP40), viral protein 35 (VP35) and nucleocapsid protein (NP) using an ELISA with a panel of 181 human sera collected from healthy controls, EBO vaccinees, and EBOV-infected survivors. Receiver Operating Characteristic (ROC) curve analysis was used to calculate sensitivity and specificity of the assay. A simple peptide-based serodiagnostic assay was used to evaluate detection of breakthrough EBOV infections in vaccinated non-human primates (NHP) in EBOV challenge studies. Findings: We identified conserved peptide sequences in EBOV VP40, VP35 and NP, produced soon after EBOV infection that are not part of the current EBO vaccine target antigens. The new ELISA-based differential serodetection assay termed 'EBOV-Detect' demonstrated >94% specificity and 96% sensitivity for diagnosis of EBOV infection. Importantly, the uninfected vaccine-trial participants scored negative in 'EBOV-Detect' assay. The results from the NHPs EBOV challenge study established that post-EBO vaccination serum scored negative in 'EBOV-Detect' and all NHPs with Ebola breakthrough infections, following EBOV challenge, were serodiagnosed positively with EBOV-Detect. Interpretation: The new 'EBOV-Detect' is a simple and sensitive serodiagnostic assay that can specifically differentiate between natural Ebola virus infected and those with vaccine-induced immunity. This could potentially be implemented as a robust diagnostic tool for epidemiology and surveillance of EBOV infections during and after outbreaks, especially in countries with mass Ebola vaccinations. Funding: The antibody characterization work described in this manuscript was supported by FDA Office of Counterterrorism and Emerging Threats (OCET) - Medical Countermeasures initiative (MCMi) grant- OCET 2019-1018 and Defense Threat Reduction Agency (HDTRA1930447) funds to S.K. |
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| MeSH term(s) | Antibodies, Viral ; Ebola Vaccines ; Ebolavirus/immunology ; Glycoproteins ; Hemorrhagic Fever, Ebola/diagnosis ; Hemorrhagic Fever, Ebola/epidemiology ; Hemorrhagic Fever, Ebola/prevention & control ; Humans ; Nucleocapsid Proteins ; Serologic Tests ; Viral Proteins |
| Chemical Substances | Antibodies, Viral ; Ebola Vaccines ; Glycoproteins ; Nucleocapsid Proteins ; Viral Proteins |
| Language | English |
| Publishing date | 2022-07-25 |
| Publishing country | Netherlands |
| Document type | Clinical Trial ; Journal Article |
| ZDB-ID | 2851331-9 |
| ISSN | 2352-3964 |
| ISSN (online) | 2352-3964 |
| DOI | 10.1016/j.ebiom.2022.104186 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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