Ultrasensitive Detection Probes for Staphylococcus aureus Enterotoxins

描述（由申请人提供）：金黄色葡萄球菌是一种严重的人类健康威胁，产生称为超抗原的外毒素，可导致一系列疾病。S.金黄色葡萄球菌超抗原与食源性疾病、肺病、肺炎、中毒性休克综合征、加重的特应性皮炎、延迟的伤口愈合和感染性心内膜炎有关。拟议工作的目的是使用ImmuVen设计的针对这些毒素的高亲和力探针，以开发超灵敏的检测方法。所述探针包括可溶性T细胞受体蛋白（IMV 01、IMV 02、IMV 03和IMV 04），其经工程化以分别与葡萄球菌肠毒素SEB、SEC、TSST-1和SEA极高亲和力结合。据认为，美国每年约有185，000例葡萄球菌食源性疾病，导致约1750例住院治疗，费用为15亿美元。的 该I期申请的假设是ImmuVen可以开发出一种高亲和力的V β蛋白，其将结合SEA（葡萄球菌食源性疾病中涉及的最重要的超抗原），并且该蛋白和其它已经表征的可溶性蛋白可以用于开发用于检测这些葡萄球菌超抗原的快速多重测定。这项工作将与大卫克兰兹教授（伊利诺伊大学）以及FDA的桑德拉·塔伦特博士和杰弗里·德格拉斯博士合作进行。具体目标是：1）工程化针对SEA的高亲和力可溶性V？; 2）开发基于V？的测定以检测SEA、SEB、SEC和TSST-1。在第二阶段的工作中，ImmuVen将进一步开发这些检测方法，成为标准化的食品检测平台和临床诊断工具。 公共卫生相关性：金黄色葡萄球菌是一个重大的人类健康威胁，产生外毒素称为超级抗原，这是一系列疾病的原因。金黄色葡萄球菌超抗原与食源性疾病、肺病、肺炎、TSS、特应性皮炎加重、伤口愈合延迟和感染性心内膜炎相关。据认为，美国每年约有185，000例葡萄球菌食源性疾病，导致约1750例住院治疗， 15亿美元。ImmuVen技术将用于开发检测工具，以识别各种样本中的葡萄球菌超抗原。

DESCRIPTION (provided by applicant): Staphylococcus aureus is a significant human health threat, producing exotoxins called superantigens, which are responsible for a range of diseases. S. aureus superantigens are associated with food-borne illnesses, pulmonary disease, pneumonia, toxic shock syndrome, exacerbated atopic dermatitis, delayed wound healing, and infectious endocarditis. The objective of the proposed work is to use high-affinity probes against these toxins, engineered by ImmuVen, to develop ultrasensitive detection assays. The probes include soluble T cell receptor proteins (IMV01, IMV02, IMV03, and IMV04) engineered for very high-affinity binding to Staphylococcal enterotoxins SEB, SEC, TSST-1, and SEA, respectively. It is thought that there are about 185,000 cases of Staphylococcal food-borne illness in the United States, annually, resulting in around 1750 hospitalizations with a cost of $1.5 billion. The hypotheses of this Phase I application are that ImmuVen can develop a high affinity Vbeta protein that will bind SEA, the most important superantigen involved in Staphylococcal food-borne illness, and that this protein and the other already characterized soluble proteins can be used to develop a rapid multiplex assay for the detection of these Staphylococcal superantigens. The work will be performed in collaboration with Prof. David Kranz (University of Illinois), and Drs. Sandra Tallent and Jeffrey DeGrasse at the FDA. The Specific Aims are: 1) To engineer a high affinity, soluble V¿ against SEA; 2) To develop V¿-based assays to detect SEA, SEB, SEC, and TSST-1. In Phase II work, ImmuVen will further develop these assays, toward both a standardized food detection platform, and a clinical diagnostic tool. PUBLIC HEALTH RELEVANCE: Staphylococcus aureus is a significant human health threat, producing exotoxins called superantigens, which are responsible for a range of diseases. Staphylococcus aureus superantigens are associated with food-borne illness, pulmonary disease, pneumonia, TSS, exacerbated atopic dermatitis, delayed wound healing, and infectious endocarditis. It is thought that there are about 185,000 cases of Staphylococcal food-borne illness in the United States, annually, resulting in around 1750 hospitalizations with a cost of $1.5 billion. ImmuVen technology will be used to develop detection tools to identify Staphylococcal superantigens in a variety of samples.