Detoxified SEB Vaccine Antigen Mutations
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current vaccines against Staphylococcus aureus exotoxin B (SEB) lack effectiveness in preventing the severe inflammatory responses and toxic shock syndrome caused by SEB, as they fail to adequately neutralize the toxin's binding to T-cell receptors and MHC Class II molecules, leading to uncontrolled cytokine release and organ damage.
Innovation Solution
Development of a detoxified SEB vaccine antigen with specific mutations at amino acid positions 21 to 25, including deletions of aa21-23 or aa22-24, which reduces the toxin's ability to bind to T-cell receptors and MHC Class II molecules, thereby preventing inflammatory responses, combined with additional mutations in the immunoglobulin superfamily binding region to enhance immunogenicity and safety.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If SEB toxin is used as vaccine antigen, then immunogenicity is improved, but toxicity increases due to uncontrolled T-cell activation and cytokine release
Solution Approach 1:
The patent applies this principle by using the SEB toxin's own structure and immunogenic properties against it. The detoxified SEB mutant maintains the immunogenic epitopes needed to stimulate protective immune responses while the mutations in the TCR binding region eliminate the harmful superantigen activity. This converts the originally harmful toxin into a beneficial vaccine antigen that triggers protective immunity without causing toxic shock.
Solution Approach 2:
The patent applies this principle by making specific amino acid substitutions in the SEB toxin sequence (positions 21-25 in the TCR binding region) that change the molecular parameters of toxin-receptor interaction. These parameter changes (amino acid substitutions) reduce binding affinity to T-cell receptors by approximately 100-fold while preserving B-cell epitopes and immunogenicity, thereby transforming the toxin from harmful to beneficial.
2Reliability
If SEB toxin binding to T-cell receptors is enhanced, then immunogenicity is improved, but harmful inflammatory responses increase
Solution Approach 1:
The patent applies this principle by making localized modifications to specific regions of the SEB toxin molecule. The amino acid substitutions are concentrated in the TCR binding region (positions 21-25) while leaving other regions, including B-cell epitopes and MHC binding regions, relatively unchanged. This local quality change allows the vaccine to maintain immunogenicity in some regions while eliminating harmful inflammatory responses in the TCR interaction region.
Solution Approach 2:
The patent applies this principle by functionally segmenting the SEB toxin into distinct regions with different fates: the TCR binding region is mutated to reduce harmful interactions, while other regions (B-cell epitopes, MHC binding regions) are preserved to maintain immunogenicity. This segmentation allows different parts of the molecule to serve different functions - some protective, some neutralized.
3Object-affected harmful factors
If SEB toxin structure is modified to reduce toxicity, then safety is improved, but immunogenicity may be reduced
Solution Approach 1:
The patent applies this principle by extracting or removing the harmful superantigen activity from the SEB toxin through targeted mutations in the TCR binding region. By taking out the toxic function (TCR activation) while preserving the immunogenic function (B-cell epitopes, MHC binding), the vaccine achieves safety without sacrificing immunogenicity. The harmful superantigenic properties are selectively extracted while beneficial properties remain.
Data Source
Figure 1
Figure 1
Figure 1
AI summary
A detoxified Staphylococcal Exotoxin B (SEB) toxin that is mutated to comprise at least two point mutations at amino acid positions 21 to 25 in the SEB toxin sequence SEQ ID NO:1, wherein said at least two point mutations comprise a deletion of any of aa21-22, aa22-23, aa23-24, aa24-25, aa21-23, aa22-24, or aa23-25, or at corresponding amino acid positions in any other naturally-occurring SEB toxin sequence that has at least 95% sequence identity to SEQ ID NO:1.