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重大的人类健康威胁，产生称为超级抗原的外毒素，可导致一系列疾病。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、伤口愈合延迟和感染性心内膜炎有关。提出的工作的目的是使用高亲和力探针针对这些毒素，由ImmuVen设计，以开发超灵敏的检测分析。这些探针包括可溶性T细胞受体蛋白（IMV01、IMV02、IMV03和IMV04），它们分别与葡萄球菌肠毒素SEB、SEC、TSST-1和SEA具有非常高的亲和力。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。这个

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.