M. tuberculosis Peptide Antigens for HIV-TB Co-infection Screening

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Solution Overview

Problem

Current diagnostic tools for tuberculosis, especially in immunocompromised individuals like those with HIV, are inadequate, failing to accurately identify asymptomatic TB cases and requiring resource-intensive methods, leading to delayed diagnosis and increased morbidity and mortality.

Innovation Solution

A method involving the detection of complexes between specific peptides and antibodies in biological samples, targeting Mtb antigens such as MS, MPT51, ESAT6, or CFP10, to predict the risk of active TB progression, allowing for early identification and monitoring of TB in HIV-positive individuals.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If culture of bacteria is used for TB diagnosis, then diagnostic accuracy is improved, but time consumption and infrastructure requirements increase significantly

Engineering Contradiction:
Improvediagnostic accuracyVSAvoidtime consumption
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent extracts and detects specific peptide antigens (ESAT-6, CFP-10, and other Mtb-specific peptides) from the complex bacterial culture system. By focusing on these specific immunogenic peptides rather than requiring full bacterial culture, the test achieves high diagnostic accuracy while dramatically reducing time requirements from weeks to hours or days.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent uses peptide copies or synthetic representations of specific Mtb antigens (ESAT-6, CFP-10) as surrogate markers for actual bacterial presence. These peptide copies can be detected through immune responses without requiring live bacterial culture, thus maintaining diagnostic accuracy while eliminating the time and infrastructure constraints of traditional culture methods.

Inventive Principle:
Principle #26Copying

2Measurement precision

If culture of bacteria is used for TB diagnosis, then diagnostic accuracy is improved, but infrastructure complexity and personnel training requirements increase

Engineering Contradiction:
Improvediagnostic accuracyVSAvoidinfrastructure requirements
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent extracts the essential diagnostic function from complex bacterial culture systems by detecting specific peptide antigens directly. This eliminates the need for sophisticated culture media, incubators, and biosafety infrastructure, making the test suitable for resource-limited settings while maintaining high diagnostic accuracy through peptide-specific detection.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent employs simple, inexpensive peptide-based detection reagents that can be used in straightforward immunological assays. These disposable or single-use peptide reagents replace expensive, complex culture systems and eliminate the need for highly trained personnel, enabling deployment in low-resource tuberculosis-endemic countries.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

3Ease of operation

If direct sputum smear microscopy is used for TB diagnosis, then ease of operation is improved, but diagnostic sensitivity deteriorates

Engineering Contradiction:
Improveease of operationVSAvoiddiagnostic sensitivity
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent changes the detection parameter from visual identification of acid-fast bacilli in smears to immunological detection of specific Mtb peptide antigens. This parameter change maintains the simplicity and ease of operation of microscopy-based methods while dramatically improving diagnostic sensitivity by detecting peptides at much lower concentrations than visible bacilli.

Inventive Principle:
Principle #35Parameter changes

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

This approach enables the early detection and monitoring of TB in immunocompromised individuals, potentially reducing TB-related morbidity and mortality by identifying asymptomatic carriers and guiding timely intervention.

Implementation Method 1

detecting formation of a complex of the peptide with an antibody in the sample

Methodology Applied
Scientific EffectAntibody-antigen binding:

Data Source

PatentUS10883989B2Peptides of <i>M. tuberculosis </i>for a screening test for HIV positive patients at high-risk for tuberculosis
Publication Date: 2021.01.05 NEW YORK UNIV
  • US10883989B2 patent drawing

AI summary

Provided are peptides suitable for early detection of active M. tuberculosis (Mtb) infection in immunocompromised individuals. The peptides can form complexes with antibodies directed to Mtb antigens MS, MPT51, ESAT6 or CFPIO. Also provided are methods for detected of complexes of the peptides and the antibodies. The presence of complexes aids in predicting risk in immunocompromised individuals of developing active tuberculosis.