Recombinant Pasteurella Multocida Toxin Epitopes for Swine Atrophic Rhinitis

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Solution Overview

Problem

Atrophic rhinitis in swine, caused by Pasteurella multocida toxin, leads to significant economic losses and growth retardation due to its infectious nature and complications with other pathogens, with existing treatments being inadequate in inducing effective immunity and posing risks such as liver damage and death in piglets.

Innovation Solution

A recombinant Pasteurella multocida toxin (rPMT) is developed, comprising specific epitopes linked with a complement component 3d amino acid sequence, designed to induce anti-PMT antibodies and enhance immune response, formulated into an immunogenic composition that includes B. bronchiseptica and P. multocida types A and D, along with a test kit for toxin detection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If full-length Pasteurella multocida toxin (PMT) is used in vaccine formulation, then comprehensive immune coverage is achieved, but severe adverse reactions including liver damage and death occur in piglets

Engineering Contradiction:
Improveimmune coverageVSAvoidtoxicity to piglets
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts only the immunogenic epitopes (specific antigenic regions) from the full-length PMT toxin while removing the toxic portions. This is achieved by identifying and isolating B-cell and T-cell epitopes that are responsible for immune recognition, thereby creating a recombinant vaccine that maintains immunogenicity without the harmful effects of the complete toxin.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent segments the PMT toxin into discrete epitopic regions that can be separately identified and reconstructed. By dividing the toxin into functional epitope units (B-cell epitopes and T-cell epitopes) and reassembling them in a controlled recombinant format, the vaccine achieves comprehensive immune coverage through multiple epitopes while avoiding the toxic effects associated with the full-length toxin structure.

Inventive Principle:
Principle #1Segmentation

2Reliability

If high dose PMT is administered to achieve effective immunity, then immune response is enhanced, but liver damage and mortality increase

Engineering Contradiction:
Improveimmune responseVSAvoidliver damage and mortality
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent fundamentally changes the dosage parameter by using recombinant epitopic sequences that are inherently safer than the full-length toxin. The recombinant vaccine can be administered at effective immunogenic doses without the toxic threshold limitations of native PMT, as the epitopic segments lack the organ-damaging properties while retaining immune-stimulating capabilities.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent converts the harmful full-length toxin into a beneficial vaccine by utilizing the immunogenic properties of specific epitopic regions. The same toxin that causes disease when administered in high doses is transformed into a protective vaccine through epitope isolation and recombinant construction, where the immune system recognizes and responds to the epitopes without suffering the toxic effects.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

3Ease of manufacture

If conventional vaccine formulations are used, then production cost is reduced, but effectiveness in preventing atrophic rhinitis is insufficient

Engineering Contradiction:
Improveproduction costVSAvoiddisease prevention effectiveness
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

The patent creates a composite recombinant vaccine structure that combines multiple epitopic sequences (both B-cell and T-cell epitopes) from PMT into a single immunogenic composition. This composite approach enhances effectiveness by stimulating multiple immune pathways simultaneously, while the recombinant production method using molecular biology techniques enables scalable manufacturing that can achieve cost-effectiveness through precision and reduced trial-and-error formulation development.

Inventive Principle:
Principle #40Composite materials

4Adaptability or versatility

If multiple pathogens are targeted in vaccine, then comprehensive protection against complications is achieved, but vaccine complexity increases

Engineering Contradiction:
Improveprotection against complicationsVSAvoidvaccine formulation complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent designs the recombinant vaccine to have multi-functional capabilities by incorporating epitopes that can recognize and respond to multiple pathogens associated with atrophic rhinitis complications. The recombinant epitopic sequences are engineered to provide cross-protection against Bordetella bronchiseptica, Pasteurella multocida type A, and type D, as well as other respiratory pathogens, making a single vaccine formulation capable of addressing multiple threats without requiring separate vaccines for each pathogen.

Inventive Principle:
Principle #6Universality (Multi-functionality)

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

The recombinant toxin effectively induces immune responses and neutralizes PMT toxicity, providing significant protection against atrophic rhinitis with improved safety and efficacy, as demonstrated by higher antibody production and reduced mortality rates in animal models.

Implementation Method 1

The recombinant toxin has at least one epitope of P. multocida toxin (PMT) to induce animals to produce anti-PMT antibody

Methodology Applied
Scientific EffectImmune response induction:

Implementation Method 2

The rPMT may further have at least one unit of partial- or full-length of the amino acid sequence of complement component 3d (C3d) to increase specific immune response

Methodology Applied
Scientific EffectComplement-mediated immune enhancement:

Implementation Method 3

The recombinant toxin effectively induces immune responses and neutralizes PMT toxicity, providing significant protection against atrophic rhinitis

Methodology Applied
Scientific EffectToxin neutralization:

Data Source

PatentEP2982683B1Recombinant pasteurella multocida toxin and application thereof
Publication Date: 2019.08.14 SBC VIRBAC BIOTECH
  • EP2982683B1 patent drawingFigure 1
  • EP2982683B1 patent drawingFigure 2A~2C
  • EP2982683B1 patent drawingFigure 3

AI summary

The invention relates to a recombinant Pasteurella multocida toxin, having at least one epitope of Pasteurella multocida toxin. When there is a plurality of the epitopes, the epitopes can be linked together with linkers. The recombinant Pasteurella multocida toxin further has at least one unit of the amino acid sequence of complement C3d, and the epitopes and the amino acid sequence of complement C3d can be linked with linkers. The invention also relates to nucleotide sequences encoding the recombinant Pasteurella multocida toxin and immunogenic compositions containing the recombinant Pasteurella multocida toxin against atrophic rhinitis.