Mycobacterium tuberculosis Antigen Peptides for Rapid Diagnostic Specificity
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Solution Overview
Problem
Current diagnostic methods for Mycobacterium tuberculosis complex infections, such as microscopic examination and culture-based methods, are inefficient due to the need for high mycobacteria concentrations and slow results, while immune response-based methods rely on specific antigens that may cause false positives in vaccinated individuals, necessitating the development of new antigens for accurate and rapid diagnosis.
Innovation Solution
Identification and use of specific M. tuberculosis antigens and fragments, particularly Rv0840c, TBFG_13463, Rv1677, Rv2654c, Rv3845, Rv1495, and Mtub2_17866, which are 12 to 18 amino acids in length and overlap by 9 to 12 amino acids, to form protein fragment libraries that effectively associate with HLA molecules and induce an immune response, enabling accurate diagnosis and potential use in vaccination.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If traditional microscopic examination or culture-based methods are used to diagnose M. tuberculosis complex infection, then the diagnosis can be obtained, but the method requires high mycobacteria concentrations and is slow
Solution Approach 1:
The patent replaces traditional mechanical microscopic examination and culture-based diagnostic methods with an immune response detection system that measures cytokine production (IFN-gamma, TNF-alpha) by T-cells in response to M. tuberculosis antigens. This substitution enables rapid detection of infection status without requiring direct visualization or cultivation of the bacteria, thereby dramatically improving diagnosis speed while maintaining high accuracy.
2Reliability
If specific M. tuberculosis antigens (such as ESAT6) are used in IGRAs to increase specificity, then the diagnostic specificity is improved, but false positives may occur in vaccinated individuals
Solution Approach 1:
The patent segments the M. tuberculosis antigen into multiple distinct peptides (including ESAT6, CFP10, and other RD1 region peptides) and uses them in combination in the IGRA assay. By testing the immune response to multiple antigenic components rather than a single antigen, the assay can more specifically identify true M. tuberculosis infections while reducing false positives in vaccinated individuals, as the vaccine-induced immunity typically targets only specific antigen components.
3Reliability
If M. tuberculosis antigens are used to detect immune response, then the diagnostic specificity is increased, but new antigens need to be developed that are different from vaccine antigens
Solution Approach 1:
The patent extracts and utilizes antigens from the RD1 genomic region of M. tuberculosis, which is absent from the BCG vaccine strain. By focusing on this specific genomic region and its encoded antigens (ESAT6, CFP10, and other RD1 peptides), the invention obtains diagnostic antigens that are naturally distinct from vaccine antigens, thereby achieving high diagnostic specificity without requiring de novo antigen development. This extraction approach simplifies the overall process while maintaining reliability.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
These antigens allow for the detection of M. tuberculosis complex infections with high sensitivity and specificity, avoiding false positives in vaccinated individuals and providing a rapid diagnostic method that complements existing immune response-based assays.
Implementation Method 1
The identified antigens contain a number T-cell and/or B-cell epitopes that associate effectively with human leukocyte antigen (HLA) molecules or antibodies respectively
Data Source
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AI summary
The present invention relates to Mycobacterium tuberculosis (M tuberculosis) proteins and immunologically active fragments (peptides or mimotope peptides) thereof. In particular, the invention relates to a group of M. tuberculosis proteins and peptides thereof that are both highly antigenic and characteristic of clinical strains of M. tuberculosis. Accordingly, the further relates to the use of these M. tuberculosis proteins or peptides in diagnosing, treating or preventing M. tuberculosis complex infection.