Chimeric VP2 Fusion Proteins for Stable VLP Peptide Incorporation
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Solution Overview
Problem
Current methods for incorporating peptides of interest into Infectious Bursal Disease Virus (IBDV) derived Virus Like Particles (VLP) often result in disruption of the VLP structure, leading to suboptimal presentation and potential biological degradation, with limited success in surface exposure or sequestration within the VLP, affecting their efficacy as vaccines, drug delivery systems, and diagnostic reagents.
Innovation Solution
The development of chimeric VP2 fusion proteins with specific insertions or substitutions within the P loop regions and outside them, allowing for the identification of preferred sites for peptide incorporation, maintaining VLP structure and enhancing formation efficiency, and enabling surface exposure or sequestration as needed for specific biological activities.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If peptides of interest are incorporated into IBDV derived VLP using current methods, then antigen presentation and immune response are improved, but VLP structure is disrupted leading to suboptimal presentation and potential biological degradation
Solution Approach 1:
The patent applies local quality by identifying specific insertion sites within the VP2 protein structure (such as the P loop region) where foreign peptides can be incorporated without disrupting the overall VLP architecture. By targeting specific local regions rather than random incorporation, the method maintains structural integrity while achieving peptide presentation functionality.
Solution Approach 2:
The VP2 protein serves as an intermediary carrier that bridges the foreign peptide of interest and the VLP structure. The patent uses VP2 as a mediator to incorporate peptides into the VLP framework, allowing the peptide to be presented on the VLP surface while the VP2 protein absorbs the structural stress of incorporation, protecting the overall VLP integrity.
2Reliability
If peptides are incorporated into VLP surface, then antigen presentation is enhanced, but VLP stability decreases leading to potential biological degradation
Solution Approach 1:
The patent employs parameter changes by modifying specific amino acid residues at defined positions within the VP2 protein to create optimal insertion sites. By changing local parameters (amino acid sequence, loop conformation) rather than the entire protein structure, the method achieves improved peptide presentation while maintaining overall VLP stability.
Solution Approach 2:
The patent applies preliminary action by pre-identifying and characterizing optimal insertion sites within the VP2 protein before actual peptide incorporation. Through computational modeling and structural analysis, the patent prepares the VP2 framework in advance with predetermined safe zones for peptide insertion, ensuring both stability and presentation quality from the outset.
3Adaptability or versatility
If foreign peptides are fused to VP2 protein, then chimeric VLP can be formed, but identification of preferred insertion sites is limited
Solution Approach 1:
The patent applies universality by developing a generalized methodology for identifying insertion sites that can be applied to any foreign peptide of interest. The method creates universal criteria (such as solvent accessibility, loop flexibility, and structural conservation) that work across different peptide types, making the site identification process systematic rather than peptide-specific.
Solution Approach 2:
The patent employs feedback mechanisms by using computational models that predict insertion outcomes and refine site selection based on predicted structural impacts. The methodology incorporates iterative feedback loops where predicted insertion structures are evaluated, and insertion site selections are refined based on this feedback to optimize both peptide presentation and VLP stability.
Data Source
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AI summary
The field of the invention refers to chimeric Virus Like Particles (VLP) derived from Birnavirus chimeric VP2 protein. In particular, the invention refers to chimeric VP2 fusion proteins which incorporate insertions and/or substitutions with one or more amino acids or particular peptide of interest while maintaining the capacity to assemble in the form of VLP. The invention identifies particular insertion and/or substitutions sites within VP2 P loop regions and outside said P loop regions. The invention also incorporates methods for the identification of preferred insertion and substitution sites within VP2 for the incorporation of particular amino acids and peptides of interest. The resulting chimeric VLP are of interest in the design of therapeutic and prophylactic vaccines as well as in the design of drug delivery systems, carriers for DNA and RNA in gene therapy, as targeted agents, in the development of antitoxins, and as diagnostic reagents.