Rodent Hepadnavirus Core Antigen Modification for Reduced Carrier Antigenicity
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Solution Overview
Problem
Current vaccine carrier platforms, such as hepadnavirus core antigens, face challenges in minimizing carrier-specific antigenicity to enhance the immune response to heterologous polypeptides, as carrier-specific antibodies can impede the immunogenicity of heterologous epitopes.
Innovation Solution
Development of rodent hepadnavirus core antigens with reduced antigenicity by modifying specific amino acid sequences to diminish the antibody response to the core antigen, allowing for enhanced antibody response to heterologous polypeptides, achieved through fusion proteins that assemble as hybrid virus-like particles (VLPs).
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If hepadnavirus core antigens are used as vaccine carrier platforms, then the immune response to heterologous polypeptides is enhanced through the carrier framework, but carrier-specific antibodies are produced that impede the immunogenicity of heterologous epitopes
Solution Approach 1:
The patent extracts and removes specific B-cell epitopic regions from the hepadnavirus core antigen sequence while preserving the essential self-assembly capabilities. This is achieved by deleting amino acid residues that correspond to immunodominant B-cell epitopes, thereby eliminating the harmful carrier-specific antibody response while maintaining the carrier's ability to enhance heterologous antigen presentation
Solution Approach 2:
The patent applies local quality modification by specifically altering only the B-cell epitopic regions of the core antigen while leaving other functional regions intact. The modified core antigen maintains its self-assembly properties and ability to present heterologous antigens, but the local modification of specific residues eliminates the harmful immune response to the carrier itself
2Object-generated harmful factors
If the core antigen sequence is modified to reduce carrier-specific antigenicity, then the antibody response to heterologous polypeptides is enhanced, but the structural integrity and self-assembly capability may be compromised
Solution Approach 1:
The patent segments the core antigen sequence into functional domains: B-cell epitopic regions that are removed or modified, T-cell epitopic regions that are preserved, and structural regions that maintain self-assembly capability. This segmentation allows selective elimination of harmful epitopes while preserving essential functional elements
Solution Approach 2:
The patent applies parameter changes by systematically modifying amino acid residues at specific positions in the core antigen sequence. These parameter changes (substitutions, deletions, or additions) are designed to eliminate B-cell epitopes while maintaining the structural parameters necessary for viral-like particle self-assembly and stability
Data Source
AI summary
The present disclosure generally relates to hepadnavirus core antigens in which one or more endogenous b cell epitopes have been effectively removed. More specifically, the present disclosure relates to rodent hepadnavirus cores modified to diminish the antibody response to the core so as to enhance the antibody response to heterologous polypeptides included therein.