Immunological and virological characterization Lassa Fever and Ebola Virus Disease survivors

拉沙热和埃博拉病毒病幸存者的免疫学和病毒学特征

• 批准号: 278993649
• 负责人: Professor Dr. Stephan Günther
• 金额: --
• 依托单位: Institute of Lassa Fever Control
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/278993649?language=en
• 关键词: Immunological; virological; characterization; Lassa; Fever

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.

埃博拉病毒（EBOV）和拉沙病毒（LASV）是负链RNA病毒，分别引起埃博拉病毒病（EVD）和拉沙热（LF）。这两种病毒都是人畜共患病，可能通过人畜共患病宿主的溢出和人传人传播给人类。LASV在西非国家几内亚、尼日利亚、利比里亚、塞拉利昂和马里流行，每年造成多达300，000例LF病例和多达6，000例死亡。LASV的天然宿主是多乳鼠Mastomys natalensis，据推测，大多数人类病例是由于接触这些啮齿动物或其排泄物引起的。关于EBOV的天然宿主知之甚少，尽管果蝠可能是候选宿主。这两种病毒引起严重的疾病，在人类的特点是高烧，免疫失调，凝血异常和多器官function.There仍然是我们的知识的重要差距，病毒学和免疫学参数，阻止从急性疾病的LF和EVD的长期恢复的过渡。因此，本提案的总体目标是了解LF和EVD生存的免疫学和病毒学参数。两个关键目标是确定（i）各种体液中病毒持续存在的程度和持续时间、血液中可测量的免疫应答以及尼日利亚LF幸存者的后遗症，和（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幸存者的免疫应答。这些目标是根据第一个项目期间取得的初步成果确定的。工作包（WP）1和WP 2将加深我们对LASV在体液中的持久性与病毒进化、长期T和B记忆的发展以及尼日利亚的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EVD病史的EBOV血清阳性个体与EVD幸存者对EBOV的体液免疫应答。WP4将重点关注EBOV暴露个体和EVD幸存者的T细胞免疫应答特征。