Modified BCG Vaccine for TB Protection Without Diagnostic Interference
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Solution Overview
Problem
Current vaccines for tuberculosis, such as Bacillus Calmette-Guérin (BCG), have variable efficacy and interfere with conventional diagnostic tests, necessitating the development of Differential Interferon-Gamma Release Assays (DIVA) to differentiate between vaccinated and infected animals, which is not feasible in all countries.
Innovation Solution
A mutant Mycobacterium cell, specifically a BCG strain with deleted genes encoding antigens like espC, esxS, MPB70, MPB83, and espA, maintains protective efficacy while allowing for diagnostic compatibility using complementary skin tests that do not cross-react with vaccinated or uninfected individuals.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If BCG vaccine is used to protect against tuberculosis, then protective efficacy is improved, but diagnostic accuracy deteriorates due to interference with tuberculin PPD skin test
Solution Approach 1:
The patent segments the BCG vaccine by deleting specific genes (esx-1, espC, espA, MPB64, MPB70, MPB83) that encode antigens responsible for cross-reactivity with PPD skin tests. This segmentation allows the vaccine to retain protective efficacy while eliminating diagnostic interference, as the deleted genes are non-essential for persistence and protection.
Solution Approach 2:
The patent extracts and removes specific antigen-encoding genes from the BCG genome that cause interference with diagnostic tests. By taking out these specific genetic elements (esx-1, espC, espA, MPB64, MPB70, MPB83), the vaccine maintains its protective function while becoming diagnostically compatible with conventional PPD-based surveillance.
2Ease of operation
If conventional PPD-based surveillance is used for diagnosis, then diagnostic simplicity is improved, but ability to differentiate vaccinated from infected animals deteriorates
Solution Approach 1:
The patent introduces a new diagnostic antigen set that serves as an intermediary solution. This new antigen panel (comprising proteins from deleted genes) acts as a mediator that enables differentiation between vaccinated and infected animals while maintaining compatibility with existing PPD-based surveillance systems. The new antigens provide the missing differentiation capability without disrupting the simplicity of conventional testing approaches.
Data Source
AI summary
The invention relates to modified Mycobacterium cells, and their uses as vaccines, and, particularly, modified Bacillus Calmette-Guérin vaccines. The invention extends to the use of the modified vaccines for vaccination applications in a wide range of animals, including cattle and humans. The invention extends to novel antigens, kits and compositions comprising these novel antigens and to their use in diagnosis. The invention also extends to apparatus comprising the modified vaccine and the antigens, and compositions comprising the antigens.