Fusion Protein Antigen Delivery for Stable Peptide Immunogenicity
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Solution Overview
Problem
Existing antigen delivery systems face challenges in improving expression, physical properties, stability, and immunogenicity, and struggle to effectively deliver antigens into immune response cells, particularly when using peptide, mRNA, or DNA forms, which have limitations such as solubility, stability, and immune response induction.
Innovation Solution
A fusion protein is developed comprising a peptide antigen linked to carrier proteins at the N-terminus and/or C-terminus, with optional affinity tags and linkers, encoded by a nucleic acid molecule and expressed using an expression vector, to enhance recombinant expression, purification, and immunogenicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If an antigen is delivered in a peptide form, then it can be synthesized and delivered, but synthesis and purification are difficult and exposure is low due to solubility and short half-life
Solution Approach 1:
The patent combines the peptide antigen with a carrier protein to form a fusion protein. This merging approach allows the peptide to benefit from the carrier protein's solubility and stability properties while maintaining its antigenic function, thereby resolving the contradiction between ease of manufacture and reliability of delivery.
Solution Approach 2:
The fusion protein represents a composite structure where the peptide antigen and carrier protein are covalently linked. This composite material approach enables the system to exhibit both the immunogenicity of the peptide and the physicochemical stability of the carrier protein, addressing both manufacturing and delivery challenges.
2Manufacturing precision
If an antigen is delivered in an mRNA form, then preparation consistency is improved, but formulation is necessary due to instability in the body and in vivo constant expression is uncertain
Solution Approach 1:
The carrier protein acts as an intermediary that protects the peptide antigen from degradation in the body. By linking the peptide to the stable carrier protein, the fusion protein achieves improved in vivo stability while maintaining the preparation consistency advantage of recombinant expression.
3Stability of the object's composition
If an antigen is delivered in a DNA form, then in vivo stability is better than mRNA, but delivery into nucleus is required and antigen expression efficiency is low
Solution Approach 1:
Instead of relying on in vivo transcription and translation of DNA, the patent extracts the antigen as a recombinant fusion protein and delivers it directly. This approach takes out the intermediate steps of nuclear delivery and in vivo expression, achieving both high stability and high expression efficiency.
4Ease of operation
If a virus vector is used, then delivery into body and immunogenicity are high, but drug efficacy is reduced due to anti-drug antibody in booster vaccination
Solution Approach 1:
The patent uses a non-viral, recombinant fusion protein approach that avoids the persistent immune response against viral vectors. Each vaccination uses fresh recombinant protein, eliminating the problem of anti-drug antibodies accumulating against the delivery vehicle, thereby maintaining efficacy in booster vaccinations.
Data Source
AI summary
The present invention relates to a fusion protein comprising a peptide antigen containing a T cell epitope, a first carrier protein linked to the N-terminus of the peptide antigen, and a second carrier protein linked to the C-terminus of the peptide antigen; a nucleic acid molecule encoding the fusion protein; an expression vector containing the nucleic acid molecule; a cell transformed with the expression vector; and an immunogenic composition comprising the fusion protein, the nucleic acid molecule, the expression vector, or the cell.