Recombinant Protein CTL Epitope Design for CMV and EBV Immunotherapy
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current vaccine strategies for human cytomegalovirus (CMV) and Epstein-Barr virus (EBV) have not shown convincing clinical efficacy and raise regulatory concerns, particularly regarding long-term health risks, and there is a need for a safe delivery technology to address CMV-associated injuries and EBV-associated cancers like nasopharyngeal carcinoma.
Innovation Solution
A recombinant protein comprising a plurality of human herpesvirus cytotoxic T cell epitopes, including proteasome liberation amino acids and TAP recognition motifs, is administered exogenously to elicit a cytotoxic T-lymphocyte immune response, which is processed through a novel TAP-independent, proteasome and autophagy-dependent pathway, enhancing immunogenicity and avoiding aggregation issues.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current vaccine strategies for CMV and EBV are used, then immunotherapy is provided, but clinical efficacy is not convincing and long-term health risks arise
Solution Approach 1:
The patent extracts only the essential immunogenic components (CTL epitopes) from the complete viral antigens. By synthesizing and administering only the critical T-cell epitope sequences rather than whole viral proteins or attenuated viruses, the invention eliminates harmful components while retaining protective immunogenicity, thereby resolving the contradiction between efficacy and safety
Solution Approach 2:
The patent segments the complex viral antigens into discrete CTL epitope units. Each epitope is a specific short peptide sequence that can be individually identified and synthesized. This segmentation allows for precise control over the immunogenic components administered, enabling effective immunotherapy without the long-term risks associated with complete vaccine strategies
2Reliability
If exogenous protein is administered to elicit CTL response, then immune response is induced, but protein aggregation occurs reducing efficacy
Solution Approach 1:
The patent applies local quality by modifying specific regions of the epitope sequences with charged amino acid residues. These localized modifications at the protein level prevent aggregation without altering the core epitope sequences that are recognized by T-cells, thereby maintaining immune response induction while eliminating aggregation problems
Solution Approach 2:
The patent changes the physicochemical parameters of the protein by incorporating charged amino acid residues. This parameter change in the protein's charge distribution and solubility characteristics prevents aggregation while preserving the immunogenic epitope structures, resolving the contradiction between inducing immune response and maintaining protein stability
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
The approach effectively induces a protective CD8+ cytotoxic T cell response, expanding virus-specific T cells and demonstrating strong effector functions, providing a safe and immunogenic solution for CMV and EBV infections and associated cancers.
Implementation Method 1
processed through a novel TAP-independent, proteasome and autophagy-dependent pathway
Implementation Method 2
processed through a novel TAP-independent, proteasome and autophagy-dependent pathway
Data Source
AI summary
An isolated protein comprises respective amino acid sequences of each of a plurality of CTL epitopes from two or more different herpesvirus antigens and further comprises an intervening amino acid or amino acid sequence between at least two of said CTL epitopes comprising proteasome liberation amino acids or amino acid sequences and, optionally, Transporter Associated with Antigen Processing recognition motifs. The isolated protein is capable of rapidly expanding human cytotoxic T lymphocytes (CTL) in vitro and eliciting a CTL immune response in vivo upon administration to an animal as an exogenous protein. Typically, the isolated protein comprises no more than twenty (20) CTL epitopes derived from cytomegalovirus and/or Epstein-Barr virus antigens.