Fusion Protein APC-Binding Domain Enhances T Cell Response
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Solution Overview
Problem
Current vaccine technologies face challenges in eliciting stable and flexible T cell-mediated immune responses, particularly in incorporating sequences from multiple infectious agent strains, and in effectively delivering antigens to antigen-presenting cells.
Innovation Solution
A fusion protein design comprising an antigen-presenting cell (APC)-binding domain or CD91 receptor-binding domain at the N-terminus, a protein transduction domain with a T cell-sensitizing signal-transducing peptide and translocation peptide at the C-terminus, and an antigen of a pathogen, where the protein transduction domain includes a fusion polypeptide with specific amino acid sequences to enhance antigen-specific T cell responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If subunit vaccines are used to incorporate sequences from multiple strains, then vaccine flexibility and adaptability improve, but the ability to elicit stable T cell-mediated immune responses deteriorates
Solution Approach 1:
The vaccine is segmented into distinct functional domains: an APC-binding domain for targeted delivery, a translocation domain for cellular entry, and antigen domains from multiple strains. This segmentation allows each component to perform its specific function optimally while maintaining overall vaccine stability and adaptability.
Solution Approach 2:
The invention uses a composite protein structure combining multiple functional elements (APC-binding domain, translocation domain, and multiple antigen sequences) into a single fusion protein. This composite structure ensures stable T cell responses while incorporating sequences from various infectious agent strains.
2Reliability
If antigens are delivered to antigen-presenting cells, then immune recognition improves, but delivery efficiency and cellular uptake deteriorate
Solution Approach 1:
The APC-binding domain acts as an intermediary that facilitates interaction between the vaccine and antigen-presenting cells by specifically binding to receptors on APC surfaces. This mediator function enhances both delivery efficiency and immune recognition by ensuring targeted cellular uptake.
Solution Approach 2:
The vaccine structure is pre-configured with APC-binding and translocation domains before antigen presentation. This preliminary arrangement of functional elements ensures efficient cellular uptake and proper intracellular trafficking to MHC presentation compartments, thereby improving both delivery efficiency and immune recognition.
Data Source
AI summary
A fusion protein for use as an immunogen enhancer for enhancing antigen-specific T cell responses is disclosed. The fusion protein comprises: (a) an antigen-presenting cell (APC)-binding domain or a CD91 receptor-binding domain; (b) a protein transduction domain; and (c) an antigen of a pathogen, wherein the APC-binding domain or the CD91 receptor-binding domain is located at the N-terminus of the fusion protein, and the antigen of the pathogen is located at the C-terminus of the protein transduction domain. The protein transduction domain is selected from the group consisting of: (i) a fusion polypeptide, comprising a T cell sensitizing signal-transducing peptide, a linker, and a translocation peptide; (ii) a T cell-sensitizing signal-transducing peptide; and (iii) a translocation peptide of 34-112 amino acid residues in length.