Recombinant BCG Vaccine Th1 Immune Shift

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Solution Overview

Problem

Current vaccines against human metapneumovirus (hMPV) fail to provide effective protection while causing inflammatory hyper-responsiveness, and there is a need for a vaccine that can induce a balanced immune response to limit disease progression without severe side effects.

Innovation Solution

A recombinant attenuated Mycobacterium strain expressing the P-protein from hMPV is used to generate a protective immunity without causing inflammatory hyper-responsiveness, shifting the immune response from Th2-type to Th1-type, promoting CD8+ cytotoxic and CD4+ helper T cell activation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If formalin-inactivated virus vaccine is used against hMPV, then vaccine coverage is achieved, but inflammatory hyper-responsiveness occurs causing severe symptoms

Engineering Contradiction:

Improvevaccine coverageVSAvoidinflammatory hyper-responsiveness

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the immune response parameters by using recombinant BCG expressing hMPV antigens instead of formalin-inactivated virus, shifting the response from Th2-type (hyper-responsive) to Th1-type (balanced), thereby achieving protection without inflammatory hyper-responsiveness

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The recombinant BCG acts as an intermediary carrier that presents hMPV antigens to the immune system in a controlled manner, inducing protective immunity without the adverse effects associated with inactivated virus vaccines

Inventive Principle:

Principle #24Intermediary (Mediator)

2Quantity of substance

If Th2-type immune response is induced, then antibody production increases, but disease progression is not limited due to lack of balanced immune response

Engineering Contradiction:

Improveantibody titerVSAvoidprotective immunity

Core Design Contradiction:

Quantity of substanceVSReliability

Solution Approach 1:

The patent changes the immune response type from Th2-type to Th1-type through the use of recombinant BCG, achieving a balanced immune response that includes both cellular immunity (CD8+ and CD4+ T cells) and humoral immunity, thereby providing reliable protective immunity

Inventive Principle:

Principle #35Parameter changes

3Reliability

If recombinant BCG expressing hMPV antigen is used, then protective immunity is induced without inflammatory hyper-responsiveness, but vaccine formulation complexity increases

Engineering Contradiction:

Improveprotective immunity without side effectsVSAvoidvaccine formulation

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The recombinant BCG serves multiple functions simultaneously: it acts as a live attenuated vaccine platform, expresses hMPV antigens, induces Th1-type immune response, and provides protective immunity without requiring additional adjuvants, thereby simplifying the overall formulation despite the complexity of recombinant technology

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentEP3054013B1Immunogenic formulation containing recombinant live BCG that express antigens of metapneumovirus (HMPV), in a suspension prepared from a lyophilisate, without requiring an adjuvant, suitable for pharmaceutical use

Publication Date: 2020.11.11 PONTIFISIA UNIVERSIDAD KATOLIKA DE CHILE

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Figure 3A~3D
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AI summary

The present invention relates to an immunogenic formulation to be used in mammals against human Metapneumovirus (hMPV), consisting of a lyophilisate of 1x109 ufc/ml of recombinant BCG that expresses the viral protein P of hMPV (of genogroups A1, A2, B1 and B2). The vaccine is derived from the full or partial product of the P gene of hMPV, capable of being used, stabilised and administered in solution without requiring adjuvants. The preparation can also contain combinations of the aforementioned formulations. The formulation is stabilised by means of lyophilisation (conservation range of between 4°C and 8°C) in order to be subsequently reconstituted in an adjuvant-free saline solution prior to use.