Immunological and virological characterization Lassa Fever and Ebola Virus Disease survivors

埃博拉病毒（EBOV）和拉沙病毒（LASV）是分别引起埃博拉病毒病（EVD）和拉沙热（LF）的负链RNA病毒。这两种病毒都是人畜共患病毒，可通过人畜共患病毒库的外溢和人与人之间的传播传播给人类。LASV在几内亚、尼日利亚、利比里亚、塞拉利昂和马里等西非国家流行，每年导致多达30万例LF病例，其中多达6000人死亡。LASV的天然宿主是多雌性大鼠Mastomys natalensis，据推测，大多数人类病例是由于与这些啮齿动物或其排泄物接触而引起的。尽管果蝠可能是候选宿主，但人们对埃博拉病毒的天然宿主知之甚少。这两种病毒在人类中引起严重疾病，其特征是高烧、免疫失调、凝血异常和多器官衰竭。在表征从急性疾病到从LF和EVD长期康复过渡的病毒学和免疫学参数方面，我们的知识仍然存在重大差距。因此，本提案的总体目标是产生关于LF和EVD生存特征的免疫学和病毒学参数的知识。两个关键目标是确定(i)病毒在各种体液中持续存在的程度和持续时间，尼日利亚LF幸存者血液中可测量的免疫反应和后遗症，以及（ii）刚果共和国农村地区亚临床EBOV感染的发生率，以及比较无临床EVD史的血清阳性个体与EVD幸存者的免疫反应。这些目标是根据第一个项目期间获得的初步结果制定的。工作包（WP）1和WP2将加深我们对尼日利亚LASV在体液中的持久性与病毒进化、长期T和B记忆的发展以及抗体动力学的关系的理解。WP3将比较与类人猿密切接触但无临床埃博拉病毒病史的埃博拉病毒血清阳性个体与埃博拉病毒病幸存者对埃博拉病毒的体液免疫反应。WP4将侧重于ebov暴露个体和EVD幸存者的T细胞免疫反应特征。

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.