Recombinant BCG Vaccine Th17 Immune Response Efficacy

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current tuberculosis vaccines, particularly BCG, provide inconclusive protection against pulmonary TB in adolescents and adults, and existing biomarkers for vaccine efficacy, such as IFNγ, are no longer considered reliable, necessitating the development of new immunologic mechanisms and biomarkers for improved vaccine design.

Innovation Solution

A method for determining vaccine efficacy by assessing the Th17 immune response, specifically using a recombinant BCG strain expressing a phagolysosomal escape domain and a urease-deficient strain, which induces a balanced Th1 and Th17 cytokine response, and a reagent kit for detecting Th17 immune responses in vaccinated subjects.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If BCG vaccination is used, then protection against tuberculous meningitis and miliary TB is achieved, but protection against pulmonary TB in adolescents and adults is inconclusive

Engineering Contradiction:

Improveprotection against pulmonary TBVSAvoidprotective efficacy

Core Design Contradiction:

ReliabilityVSQuantity of substance

Solution Approach 1:

The patent modifies the BCG vaccine by changing genetic parameters - specifically introducing a phagolysosomal escape domain and deleting the urease gene (ΔureC). This creates a recombinant BCG strain (rBCG) with altered immunogenicity that induces both Th1 and Th17 cytokine responses, potentially improving protection against pulmonary TB while maintaining safety.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The recombinant BCG strain combines multiple functional elements: the original BCG backbone providing safety and basic immunogenicity, plus a phagolysosomal escape domain for enhanced intracellular survival, plus deletion of urease C to control pH homeostasis. This composite construct aims to elicit balanced Th1 and Th17 responses for superior protection.

Inventive Principle:

Principle #40Composite materials

2Measurement precision

If IFNγ biomarker is used to determine vaccine efficacy, then immune response is measured, but it is no longer considered a reliable marker of protective immunity

Engineering Contradiction:

Improvereliability of protective immunity markerVSAvoidcorrelate of protection

Core Design Contradiction:

Measurement precisionVSReliability

Solution Approach 1:

The patent introduces IL-17 as an intermediary biomarker to complement or replace IFNγ. By measuring both Th1 (IFNγ) and Th17 (IL-17) cytokine responses, the patent identifies a more reliable marker profile for protective immunity. The Th17 response, specifically, appears to be a distinguishing feature of protective immunity induced by rBCG.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Reliability

If new vaccine candidates are tested in clinical trials, then efficacy is determined, but trial duration and complexity increase

Engineering Contradiction:

Improvevaccine efficacy determinationVSAvoidtrial duration

Core Design Contradiction:

ReliabilityVSLoss of time

Solution Approach 1:

The patent establishes feedback mechanisms through the identification of biomarkers (Th17 response, IL-17 production) that can be measured during clinical trials. These biomarkers provide real-time feedback on vaccine efficacy, allowing for faster determination of whether a vaccine candidate is effective, thereby reducing trial duration and enabling parallel testing of multiple candidates.

Inventive Principle:

Principle #23Feedback

Data Source

PatentEP2656070B9Determination of the efficacy of a live recombinant Anti-mycobacterial vaccination

Publication Date: 2017.01.04 VAKZINE PROJEKT MANAGEMENT GMBH

AI summary

The invention relates to methods and reagents for determining efficacy of vaccine, particularly of a tuberculosis vaccine.