Immunological and virological characterization Lassa Fever and Ebola Virus Disease survivors

点击翻译按钮获取中文摘要

Ebola virus (EBOV) and Lassa virus (LASV) are negative-strand RNA viruses that cause Ebola virus disease (EVD) and Lassa fever (LF), respectively. Both viruses are zoonotic and may be transmitted to humans via spillover from the zoonotic reservoir and via human-to-human transmission. LASV is endemic in the West African countries of Guinea, Nigeria, Liberia, Sierra Leone, and Mali, and causes up to 300,000 LF cases with up to 6,000 deaths per year. The natural host of LASV is the multimammate rat Mastomys natalensis and it is assumed that most human cases arise from contact with these rodents or their excreta. Less is known about the natural host of EBOV, though fruit bats are likely candidate reservoirs. Both viruses cause severe disease in humans characterized by high fever, immune dysregulation, coagulation abnormalities and multiorgan failure.There are still important gaps in our knowledge on the virological and immunological parameters that characterise the transition from acute disease to long-term recovery from LF and EVD. Therefore, the overall goal of this proposal is the generation of knowledge on the immunological and virological parameters that characterize LF and EVD survival. The two key objectives are to determine (i) the magnitude and duration of viral persistence in various body fluids, the immune responses measurable in blood, and sequelae in LF survivors in Nigeria, and (ii) the incidence of subclinical EBOV infection in rural areas of the Republic of the Congo, as well as to compare the immune response of seropositive individuals without history of clinical EVD with that of EVD survivors. These objectives are based on the preliminary results obtained during the first project period. Workpackage (WP)1 and WP2 will deepen our understanding of LASV persistence in body fluids in relation to virus evolution, development of long-term T and B memory, and antibody kinetics in Nigeria. WP3 will compare the humoral immune responses to EBOV in EBOV-seropositive individuals that live in close contact with great apes but have no history of clinical EVD with that of EVD survivors. WP4 will be focused on the characterization of T cell immune response in EBOV-exposed individuals and EVD survivors.