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.
Public Health Relevance Statement: 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.
NIH Spending Category: Biodefense; Bioengineering; Digestive Diseases; Emerging Infectious Diseases; Food Safety; Infectious Diseases; Lung
Project Terms: Affinity; Atopic Dermatitis; base; Binding (Molecular Function); Biological Assay; Biotechnology; Clinical; Collaborations; cost; Detection; Development; Diagnosis; Diagnostic; Diagnostic tests; Disease; Disease Management; Disease Outbreaks; Endocarditis; Engineering; Enterotoxins; Enzyme-Linked Immunosorbent Assay; Escherichia coli; Exotoxins; Food; foodborne; foodborne illness; foodborne outbreak; Foundations; Frequencies (time pattern); gastrointestinal; Gram-Positive Bacteria; Health; Hospitalization; Human; Illinois; Immunoglobulin Variable Region; Impaired wound healing; Ingestion; innovation; interest; Lead; Legal patent; Licensing; Lung diseases; Marketing; mutant; new technology; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Pneumonia; Preclinical Testing; Production; Protein Engineering; Proteins; receptor; Rights; Sampling; Small Business Innovation Research Grant; Specificity; staphylococcal enterotoxin; Staphylococcal Enterotoxin B; Staphylococcus aureus; Streptococcus pyogenes; Superantigens; System; T-Cell Receptor; technological innovation; Technology; Testing; Therapeutic; tool; Toxic Shock Syndrome; Toxic Shock Syndrome Toxin-1; Toxin; United States; Universities; Work; Yeast
