Attenuated Pasteurella multocida Vaccine Strains
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Solution Overview
Problem
Current vaccines for Pasteurella multocida in cattle are ineffective and lack reliable protection against infections, particularly in young calves, and existing attenuated strains have stability concerns for long-term field use.
Innovation Solution
Development of attenuated Pasteurella multocida strains with specific gene deletions, such as hyaD and nanPU, to create a live attenuated vaccine that elicits a safe and effective immune response in bovines, including a double knockout mutant, with the strains being formulated into a vaccine composition and adjuvanted for enhanced immunogenicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional bacterins and live streptomycin-dependent mutant vaccines are used, then vaccine coverage is provided, but field efficacy is questionable and reliable protection is not achieved
Solution Approach 1:
The patent modifies the virulence parameters of P. multocida by deleting specific virulence genes (hyaD, nanPU, and their combination) to create attenuated strains that maintain immunogenicity while reducing pathogenicity. This gene deletion strategy changes the bacterial parameters to achieve both reliability and adaptability in vaccine protection
Solution Approach 2:
The patent creates composite vaccine formulations by combining multiple attenuated strains (ΔhyaD, ΔnanPU, and ΔhyaDΔnanPU double mutant) with adjuvants. This composite approach integrates different attenuated strains with complementary protective effects to achieve broad and reliable protection against P. multocida infections
2Object-affected harmful factors
If virulent P. multocida strains are used for vaccination, then broad immune response is elicited, but safety concerns arise particularly in young calves
Solution Approach 1:
The patent extracts and removes specific virulence genes (hyaD and nanPU) from the P. multocida genome to create attenuated strains. By taking out these harmful virulence factors while retaining other immunogenic components, the vaccine elicits broad immune responses without the dangerous virulence associated with wild-type strains
Solution Approach 2:
The patent converts the harmful virulence of P. multocida into a benefit by using controlled gene deletion to create live attenuated vaccines. The attenuated strains retain enough biological activity to stimulate strong immune responses while being safely reduced in virulence, particularly for use in young calves
3Object-generated harmful factors
If existing attenuated strains are used, then safety is improved, but stability concerns arise for long-term field use
Solution Approach 1:
Instead of attempting to stabilize virulent strains, the patent inverts the approach by creating stability through targeted gene deletions. The ΔhyaD and ΔnanPU mutations create fundamentally stable attenuated phenotypes that cannot revert to virulence, ensuring long-term compositional stability for field use
Solution Approach 2:
The patent permanently changes the genetic parameters of P. multocida by deleting specific genes (hyaD, nanPU) to create stable attenuated strains. These genetic modifications ensure long-term stability of the attenuated phenotype, preventing reversion to virulence while maintaining safety for extended field use
Data Source
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AI summary
The present invention provides attenuated P. multocida strains that elicit an immune response in animal P. multocida, compositions comprising said strains, methods of vaccination against P. multocida, and kits for use with such methods and compositions. The invention further provides novel, genetically-engineered mutations in P. multocida hyaD and nanPU genes, which are useful in the production of novel attenuated P. multocida bacterial strains.