GH19-003, Epidemiology and Immunity to Ebola Virus and Other Emerging Viral Infections in Liberia

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PROJECT SUMMARY Liberia, a resource rich but economically poor country, continues to struggle with growth and recovery following a 14-year civil war that destroyed its infrastructure. The 2014-16 Ebola Virus Disease (EVD) epidemic had a devastating impact in West Africa resulting in 10,678 suspected, probable and confirmed cases and 4,810 deaths in Liberia. As not all individuals infected with Ebola virus (EBOV) sought medical attention or received laboratory confirmation of EVD, the full magnitude of the outbreak is still unknown. While the West African outbreak permitted advancement of scientific inquiry into the natural history, sociobehaviorial context, and effectiveness of countermeasures for EVD, significant gaps in knowledge remain about post-Ebola sequelae, immune responses to Ebola virus infection and disease, and durability of immunity over time. Another subject of concern is the persistence of EBOV in immunologically protected sites of EVD survivors (and potentially undiagnosed Ebola virus infections). Persistent infection has resulted in sexual transmission of the virus and subsequent clusters of disease following the end of widespread transmission. This viral persistence combined with minimal available seroepidemiological surveillance data for Ebola and other viruses with epidemic potential in West Africa poses a continued risk for resurgence of Ebola virus infection or disease cases and the possibility of new clusters or large-scale outbreaks originating from previously reported or unrecognized infections. In line with the mission of CDC, this project is aimed at establishing a serological baseline for a future surveillance platform, allowing the study of underlying etiologies, characteristics, and response to emerging infections. This will advance our combined knowledge on priority epidemic-prone viral diseases in Liberia, allowing development of strategies to prevent future outbreaks through a combination of conventional, targeted serosurveillance and disease and intervention modeling. We propose to address the overall research goals with the following four Specific Aims: (1) Develop and optimize virus-specific antibody-detection assays. Multiplex immunoassays for detection of antibody responses to relevant viral antigens will be further refined. (2) Establish assays to document cell-mediated immune responses in humans against emerging viral pathogens. Cell-mediated immunity in survivors of Ebola and Lassa virus infections will be documented using flow cytometry and transcriptome analysis to develop an immunological signature for these infections. (3) Determine a serological baseline of evidence of Ebola virus and other emerging viral infections throughout Liberia. Samples from all health districts in Liberia will be collected and analyzed for evidence of prior viral infections. (4) Conduct temporal assessment of the immune status and associated health outcomes in Ebola and Lassa virus symptomatic and asymptomatic survivors in comparison to the seronegative population. Following cohorts of persons previously infected with EBOV or Lassa virus will allow establishment of a time course for waning immunity to these priority pathogens.