Human Monoclonals to Dengue Virus

人类单克隆登革热病毒

• 批准号: 9150965
• 负责人: ANUJA MATHEW
• 金额: $ 4.39万
• 依托单位: UNIVERSITY OF RHODE ISLAND
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-10-01 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9150965
• 关键词: Human; Monoclonals; Dengue; Virus

Dengue viruses (DENV) cause an important and re-emerging viral disease, resulting in an estimated 100 million infections globally each year. Substantial evidence indicates that the pathogenesis of severe dengue disease involves a complex interaction between viral replication and host immune responses. Pre-existing DENV antibodies are a major risk factor to develop severe DENV disease. An improved understanding of the relationship between antibody titers in the sera and the ability of memory B cells to reactivate following a secondary heterologous DENV infection would be invaluable to guide the development of an effective dengue vaccine. These efforts have been significantly inhibited by the lack of a reliable small animal model that recapitulates the interactions between virus infection and host immunity that cause severe disease in humans. The overall objective of this project is to evaluate novel and existing strains of humanized mice including Bone marrow/Liver/Thymus NOD-scid IL2rγnull mice (BLT- NSG) as a reliable small animal model for the study of dengue virus infection, immunity, and pathogenesis. For this proposal we will examine antibody and B cell responses to controlled primary and secondary DENV infections in BLT-NSG mice. We will address the objectives through the following specific aims. 1. Investigate the specificity and functionality of DENV-specific antibody responses generated during primary and secondary viral infections in BLT-NSG mice. 2. Characterize B cell subsets in blood and tissue resident cells that respond to primary and secondary DENV infections in BLT-NSG mice.

登革热病毒（DENV）引起了重要的，重新散发病毒疾病，重新占据 估计全球1亿个感染 严重登革热疾病的发病机理涉及 病毒复制和宿主免疫反应。 发生严重DENV疾病的风险因素。 血清中抗体滴度与记忆B细胞的能力之间的关系 继发性异源DENV感染后重新激活对于 指导有效的登革热疫苗。 由于缺乏可靠的小动物模型而显着抑制 病毒感染与宿主免疫之间的相互作用，导致严重疾病 人类。 人源化小鼠包括骨髓/肝脏/胸腺nod-scidIL2RγNull小鼠（BLT- NSG）是一种可靠的小动物模型，用于研究登革热病毒感染，免疫力， 和发病机理。 BLT-NSG小鼠中受控的原发性和继发性DENV感染。 我们将解决以下特定目标的目标。 1。研究DENV特异性抗体反应的特异性和功能 在BLT-NSG小鼠的初次和继发病毒感染期间产生。 2。表征血液和组织驻留细胞中的B细胞子集的反应 BLT-NSG小鼠的原发性和继发性DENV感染。