Mutated NetB Epitope Polypeptide for Necrotic Enteritis Vaccine
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Solution Overview
Problem
Current vaccine development efforts have not been successful in effectively protecting chickens against avian necrotic enteritis (NE) caused by Clostridium perfringens, particularly due to the lack of understanding of the molecular basis of NetB toxin's toxicity and the limited efficacy of existing immunization strategies.
Innovation Solution
Development of NetB epitope polypeptides with specific mutations, such as substitutions at positions 130-297, which reduce toxicity while maintaining the ability to bind antibodies, providing partial or complete protection against Clostridium perfringens infection in chickens.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If wild-type NetB polypeptide is used as vaccine antigen, then immunogenicity is achieved, but high toxicity is caused
Solution Approach 1:
The patent applies parameter changes by introducing specific amino acid substitutions at positions 130-297 of the NetB polypeptide sequence. These mutations alter the toxic properties of the protein while preserving its immunogenic epitopes, thereby changing the parameters of toxicity without compromising vaccine efficacy
Solution Approach 2:
The invention extracts the immunogenic epitopes from the toxic wild-type NetB protein by creating mutated versions that retain antibody-binding capability but have reduced toxicity. The mutated polypeptides are separated from the harmful toxic properties while maintaining the protective immunological function
2Reliability
If alpha toxin is targeted for vaccination, then some protection is achieved, but NetB-mediated virulence remains unaffected
Solution Approach 1:
Instead of targeting the traditionally studied alpha toxin, the patent inverts the approach by focusing on NetB as the primary vaccine target. This inversion is based on new evidence that NetB, not alpha toxin, is the key virulence factor for necrotic enteritis, thereby achieving better protective coverage
3Object-affected harmful factors
If formaldehyde treatment is used to reduce toxicity, then immunogenicity is maintained, but manufacturing complexity increases
Solution Approach 1:
The patent replaces the complex multi-step formaldehyde treatment process with a simpler genetic mutation approach. The mutated polypeptides can be produced directly through recombinant expression systems, eliminating the need for lengthy chemical treatment and purification steps required for formaldehyde toxoid preparation
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 mutated NetB epitope polypeptides offer reduced toxicity and effective protection against Clostridium perfringens infection, reducing the probability of infection in chicken populations, as demonstrated by their ability to bind antibodies and induce an immune response.
Implementation Method 1
the polypeptide being capable of binding an antibody which binds to the polypeptide of sequence SEQ ID NO:1
Data Source
AI summary
There is provided a NetB epitope polypeptide comprising at least 10 contiguous amino acids from SEQ ID NO:1 and comprising a mutation in at least one position between amino acids 130 and 297 as compared with the equivalent position in SEQ ID NO:3, the mutation preferably being located within a rim domain, the polypeptide being capable of binding an antibody which binds to SEQ ID NO:1 and having reduced toxicity compared with the toxicity of SEQ ID NO:1. The polypeptide is useful to vaccinate a subject against infection by Clostridium perfringens.