Split-Core Hepatitis B Core Antigen Vaccine Carrier
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing hepatitis B virus core antigen-based vaccine carriers face limitations in presenting foreign molecules due to structural constraints, leading to inadequate immune response, especially in individuals chronically infected with HBV, and difficulties in distinguishing between infection and vaccination due to strong anti-HBcAg responses.
Innovation Solution
The split-core system, which separates the hepatitis B virus core protein into two parts that spontaneously reassemble, allowing foreign molecules to be fused to either the N-terminal or C-terminal fragment, enabling flexible presentation and overcoming structural limitations for improved immune response and reduced anti-HBcAg response.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If foreign molecules are inserted into the hepatitis B core protein to create vaccine carriers, then the immune response is enhanced, but the structural integrity and self-assembly capability of the core particles deteriorate
Solution Approach 1:
The core protein is divided into two separate fragments (N-terminal fragment and C-terminal fragment) that can independently fold and assemble. The foreign molecule is fused to one fragment, allowing the other fragment to provide structural stabilization. This segmentation resolves the contradiction by separating the functional domain (foreign molecule presentation) from the structural domain (capsid formation), enabling both immune response enhancement and structural integrity maintenance.
2Reliability
If the hepatitis B core protein is used as a vaccine carrier, then strong immune response is elicited, but it becomes difficult to distinguish between infection and vaccination due to strong anti-HBcAg responses
Solution Approach 1:
The immunodominant c/e1 epitope (amino acids 73-94) is removed or significantly modified in the vaccine construct. By extracting this highly immunogenic region from the core protein used in vaccination, the vaccine elicits immune responses against the foreign molecule without triggering strong anti-HBcAg responses. This allows clear distinction between infection (which produces anti-HBcAg antibodies) and vaccination (which produces antibodies against the foreign antigen).
3Reliability
If foreign sequences are linked to both N and C termini of the core protein, then stable presentation is achieved, but the selection and insertion of suitable foreign sequences becomes restricted
Solution Approach 1:
The system transitions from a static dual-linkage configuration to a dynamic single-linkage configuration. The foreign molecule is linked to only one terminus (N or C) of the core protein fragment, allowing flexible selection of foreign sequences without requiring compatibility with both termini. This dynamic approach enhances versatility in foreign sequence selection while maintaining stable presentation through the fragment assembly mechanism.
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
This approach enhances the presentation of foreign molecules, stimulates both humoral and cellular immune responses, and reduces the anti-HBcAg response, making it suitable for individuals chronically infected with HBV and improving vaccine efficacy by allowing the use of non-human HBV core proteins as carriers.
Implementation Method 1
The particles consist of the N-terminal fragment (coreN) and the C-terminal fragment (coreC) of the core protein of a hepatitis B virus... the core protein being able to bind capsid-like particles
Data Source
AI summary
Disclosed are split-core carrier substance which, as separate polypeptide, have the core N domain and the core C domain of the core protein of a hepatitis B virus and at least one foreign molecule against which an immune response is to be induced. According to the invention, the foreign molecule, especially the heterologous foreign amino acid sequence, is fused to the C terminus or the core N domain or to the N terminus of the core C domain and the core protein can form capsid-like particles. The invention also relates to the associated production method.