Immune Correlates of Protection form Rift Valley Fever Virus
裂谷热病毒保护的免疫相关性
基本信息
- 批准号:9551170
- 负责人:
- 金额:$ 8.74万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-09-01 至 2020-01-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION (provided by applicant): Candidate: I hold an MD/PhD and am a pediatric infectious disease physician and basic scientist. Every step in my career journey has been focused towards the goal of becoming a physician scientist. I am at the beginning of my first faculty appointment, and find that this time is a unique one in which I have the opportunity to broaden my skills in the area of immunology. My main goal during the time of the K08 award is to develop expertise in state of the art experimental immunology. I will achieve this via didactic instruction, accompanied by mentorship from several virologists and immunologists in the context of the proposed research project examining the role of CD4 T cells in preventing Rift Valley fever virus encephalitis. My primary mentor, Paul Spearman, MD, is a viral immunologist as well as a physician scientist and my division director. As a career and science mentor, he will guide my research progress over the time of the award, facilitate advisory committee meetings, and provide career development assistance including R01 proposal development and review. In the next 5 years I plan to capitalize on these newly gained skills to establish myself as an expert
in studies of the interaction between host immune responses and emerging viruses. Environment: My appointment is in the Division of Pediatric Infectious Disease, Department of Pediatrics in the Emory University School of Medicine. The Department of Pediatrics at Emory is ranked ninth in the 2014 NIH rankings for Departments of Pediatrics for NIH based funding. This Department has an established track record of supporting junior physician scientists. There are numerous resources available to me at Emory for both research and career development. The experiments will be performed in the BSL-3E space at the US Centers for Disease Control and Prevention, where I hold a guest researcher appointment in the Viral Special Pathogens Branch and will have the expert mentorship and support from Christina Spiropoulou, PhD, team lead. Research: Rift Valley fever virus (RVFV) is a mosquito borne virus that causes disease in people and animals in Africa and the Middle East. In the past few years several new live attenuated vaccines have become available for use in livestock. The basis of attenuation for all of these vaccines is the deletion/modification of the viral virulence factor, NSs. These Del NSs viruses generate a protective immune response in animals, in that vaccinated animals are protected from challenge with wild-type virus. However, until recently, little was known about which specific components of the immune response were important for this protection. We reported that mice that were depleted of their CD4 T cells developed encephalitis following infection with the Del NSs virus, suggesting that some function of the CD4 T cell was important for providing protection from this virus. In this proposal, we will first determine the mechanism (viral vs. immune mediated) of Del NSs encephalitis in the CD4 depleted mice. Then, since there are at least 5 different types of CD4 T cells with various roles, we will characterize the CD4 T cell subsets that are activated and functional during Del NSs infection and begin to examine each subset individually to determine how they contribute to protection from encephalitis. Finally the role of B cells and antibodies in protection from encephalitis will be defined. These experiments will establish correlates of immunity against RVFV in the mouse model. These data will be used to design future studies targeted at examining immune correlates of protection in humans.
描述(由申请人提供):候选人:我拥有MD/PhD学位,是儿科传染病医生和基础科学家。我职业生涯的每一步都是为了成为一名医生科学家。我在我的第一个教师任命的开始,并发现这是一个独特的时间,我有机会扩大我在免疫学领域的技能。在K 08奖期间,我的主要目标是发展最先进的实验免疫学的专业知识。我将通过教学指导来实现这一目标,同时在拟议的研究项目中,研究CD 4 T细胞在预防裂谷热病毒脑炎中的作用,并由几位病毒学家和免疫学家提供指导。我的主要导师,医学博士保罗斯皮尔曼,是一位病毒免疫学家,也是一位内科科学家和我的部门主任。作为一个职业和科学导师,他将指导我的研究进展在获奖的时间,促进咨询委员会会议,并提供职业发展援助,包括R 01提案的开发和审查。在接下来的5年里,我计划利用这些新获得的技能,使自己成为一名专家
研究宿主免疫反应和新出现的病毒之间的相互作用。环境:我的任命是在儿科传染病科,儿科系在埃默里大学医学院。埃默里大学的儿科系在2014年NIH儿科系排名中排名第九。该部门在支持初级医生科学家方面有着良好的记录。有许多资源可供我在埃默里大学的研究和职业发展。这些实验将在美国疾病控制和预防中心的BSL-3E空间进行,我在那里担任病毒特殊病原体分支的客座研究员,并将得到团队负责人Christina Spiropoulou博士的专家指导和支持。研究:裂谷热病毒(RVFV)是一种蚊子传播的病毒,在非洲和中东的人和动物中引起疾病。在过去的几年中,几种新的减毒活疫苗已可用于牲畜。所有这些疫苗减毒的基础是病毒毒力因子NS的缺失/修饰。这些Del NSs病毒在动物中产生保护性免疫应答,因为接种疫苗的动物被保护免受野生型病毒的攻击。然而,直到最近,人们对免疫反应的哪些特定成分对这种保护作用很重要还知之甚少。我们报道了耗尽其CD 4 T细胞的小鼠在感染Del NSs病毒后发生脑炎,这表明CD 4 T细胞的某些功能对于提供对该病毒的保护是重要的。在本提案中,我们将首先确定CD 4缺失小鼠中Del NS脑炎的机制(病毒介导与免疫介导)。然后,由于至少有5种不同类型的CD 4 T细胞具有不同的作用,我们将表征在Del NS感染期间被激活和起作用的CD 4 T细胞亚群,并开始单独检查每个亚群以确定它们如何有助于保护免受脑炎。最后,将明确B细胞和抗体在预防脑炎中的作用。这些实验将在小鼠模型中建立针对RVFV的免疫相关性。这些数据将用于设计未来的研究,旨在检查人类免疫保护的相关性。
项目成果
期刊论文数量(0)
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Anita K McElroy其他文献
Anita K McElroy的其他文献
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{{ truncateString('Anita K McElroy', 18)}}的其他基金
Innate immune recognition and response to Rift Valley fever virus
对裂谷热病毒的先天免疫识别和反应
- 批准号:
10512807 - 财政年份:2022
- 资助金额:
$ 8.74万 - 项目类别:
Immune correlates of protection from Rift Valley fever virus
预防裂谷热病毒的免疫相关性
- 批准号:
9109849 - 财政年份:2016
- 资助金额:
$ 8.74万 - 项目类别:
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