S-Type MAP Tripeptide Antigens for Specific Infection Detection
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Solution Overview
Problem
Current diagnostic tests for Mycobacterium avium subsp. paratuberculosis (Map) infections, particularly S-type strains, are not specific and sensitive enough, leading to high false positives and undetermined results, and require expensive laboratory equipment, making early detection of Johne's disease and Crohn's disease challenging.
Innovation Solution
Development of a specific tripeptide antigen, H-D-Phe-N-Methyl-L-Val-L-Ala-OMe, and its derivatives for use in diagnostic tests that can detect humoral and cell-mediated responses in animals, allowing for early and accurate identification of S-type Map infections without the need for expensive equipment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If current diagnostic tests for Map infections are used, then detection capability is provided, but specificity and sensitivity are insufficient leading to high false positives and undetermined results
Solution Approach 1:
The invention segments the diagnostic approach by using specific tripeptide antigens (H-D-Phe-N-Methyl-L-Val-L-Ala-OMe and derivatives) that target only S-type Map strains, rather than using broad-spectrum antigens that cross-react with multiple mycobacterial species. This segmentation enables specific detection of S-type Map infections while avoiding false positives from other mycobacteria.
Solution Approach 2:
The invention changes the antigenic parameter by using modified tripeptide structures with specific amino acid sequences and chemical modifications (N-methyl substitution, O-methyl esterification) that are unique to S-type Map strains. These parameter changes in antigen structure provide high specificity for detecting S-type Map infections while maintaining sensitivity.
2Measurement precision
If expensive laboratory equipment is used for Map detection, then detection capability is improved, but cost and accessibility are reduced
Solution Approach 1:
The invention employs simple tripeptide antigens that can be used in basic immunoassay formats (ELISA, lateral flow) without requiring expensive specialized equipment. The tripeptide antigens can be synthesized chemically and used in disposable test formats, making the diagnostic accessible in field settings and routine laboratories without advanced instrumentation.
3Loss of time
If early detection of Map infections is attempted, then treatment effectiveness is improved, but diagnostic accuracy is reduced due to latent infection challenges
Solution Approach 1:
The invention enables preliminary detection of S-type Map infections during the latent phase by using highly specific tripeptide antigens that elicit detectable immune responses even before clinical symptoms appear. The specific antigen structure allows detection of low-level infections early in the disease process, enabling intervention before the animal develops clinical Johne's disease.
Data Source
AI summary
The present invention is directed to an isolated synthetic tripeptide of formula H-D-Phe-N-Methyl-L-Val-L-Ala-OMe (SEQ ID NO: 1), or a derivative thereof, and to the corresponding lipotripeptides, which are specific to Mycobacterium avium subsp. paratuberculosis (Map) S-type strain, as well as derivatives and conjugates thereof. The invention also concerns the use of these antigens in different methods and tests for detecting Map infection, especially by detecting humoral response and cell mediated response of infected animals. The invention is also directed to a genetic signature of Map and a mass spectrometry and NMR spectroscopy signature of Map presence or infection.