Temperature-Sensitive Mycoplasma Hyopneumoniae Vaccine Strain

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Solution Overview

Problem

Current vaccines against Mycoplasma hyopneumoniae do not provide full protection against enzootic pneumonia in swine, despite their widespread use, as they are either killed or inactivated, which limits their effectiveness in inducing robust immunity.

Innovation Solution

A live, attenuated Mycoplasma hyopneumoniae strain, designated as ts19, is developed through chemical mutagenesis and selected for temperature sensitivity, ensuring it remains viable and non-revertible to virulence, providing a more effective vaccine by mimicking the natural infection while being safe for use.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If killed or inactivated M. hyopneumoniae preparations are used as vaccines, then the vaccine is safe for use, but the protective immunity is insufficient

Engineering Contradiction:
Improveprotective immunityVSAvoiddisease severity
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies parameter changes by creating a temperature-sensitive mutant strain of M. hyopneumoniae that grows at lower temperatures (33-37°C) but is inhibited at higher temperatures (39-41°C). This temperature sensitivity parameter allows the bacterium to replicate in the vaccinated pig (maintaining immunogenicity) while being controlled and safe for use, resolving the contradiction between providing sufficient protective immunity and ensuring safety.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent introduces dynamic control through temperature-sensitive growth characteristics. The vaccine strain dynamically adjusts its replication based on host temperature conditions - thriving in the cooler pig body (33-37°C) to provide immunity while being naturally restricted at higher temperatures (39-41°C), ensuring safety without requiring inactivation.

Inventive Principle:
Principle #15Dynamics

2Reliability

If live attenuated vaccine strain is used, then protective immunity is enhanced, but the strain may revert to virulence

Engineering Contradiction:
Improveprotective immunityVSAvoidreversion to virulence
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent converts the potentially harmful temperature-sensitive growth characteristic into a beneficial safety mechanism. The temperature sensitivity, which could theoretically allow reversion, is instead used as a control mechanism - the strain naturally fails to replicate at pig body temperatures (39-41°C), preventing virulence reversion while maintaining immunogenicity at lower temperatures (33-37°C).

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

Solution Approach 2:

The patent employs a disposable vaccine strain that is deliberately designed to be non-revertible. The temperature-sensitive mutant strain undergoes multiple passages and genetic modifications that permanently fix the attenuation phenotype, ensuring it cannot revert to virulence. Once used, the strain is discarded, eliminating any long-term risk of reversion.

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

3Reliability

If chemical mutagenesis is applied to create attenuated strain, then the strain becomes temperature sensitive, but the process is time consuming and produces false results

Engineering Contradiction:
Improvetemperature sensitivityVSAvoidselection time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The patent applies preliminary action by performing chemical mutagenesis and initial screening in controlled laboratory conditions before final vaccine strain selection. The temperature-sensitive mutants are identified and characterized in advance through systematic passage and testing, allowing the most promising strains to be selected efficiently without time-consuming trial-and-error processes in the field.

Inventive Principle:
Principle #10Preliminary action

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 live attenuated vaccine strain ts19 confers protective immunity against enzootic pneumonia, demonstrating safety and efficacy in reducing lung lesions and disease severity, with a determined minimum protective dose of 10^4 CCU/mL, outperforming commercial inactivated vaccines in protective index and weight gain analysis.

Implementation Method 1

The inventors subjected a Mycoplasma hyopneumoniae isolate to chemical mutagenesis and selected clones that were temperature sensitive

Methodology Applied
Scientific EffectChemical mutagenesis:

Implementation Method 2

The inventors freeze dried the live mutant bacteria and found that the bacteria could be reconstituted after a week and remain viable after serial passaging

Methodology Applied
Scientific EffectSerial passaging:

Data Source

PatentEP2453913B1A temperature sensitive vaccine strain of mycoplasma hyopneumoniae and uses thereof
Publication Date: 2016.06.22 BIOPROPERTIES
  • EP2453913B1 patent drawingFigure 1
  • EP2453913B1 patent drawingFigure 2
  • EP2453913B1 patent drawingFigure 3

AI summary

The present invention relates to a Mycoplasma hyopneumoniae vaccine strain comprising a mutation in at least one of the genes listed or as deposited with the National Measurements Institute (Australia) under accession number NM04/41259, which strain is temperature sensitive and attenuated, a vaccine comprising such strains and methods and uses thereof.