Variable Epitope Libraries for Targeting Mutated Antigens
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Solution Overview
Problem
Current vaccine development faces challenges in addressing immune escape mechanisms employed by pathogens with genetic variability, as they mutate amino acids in epitopes, evading immune recognition and response.
Innovation Solution
The development of variable epitope libraries (VELs) containing mutated versions of epitopes derived from antigens, including CTL-derived epitopes of survivin, to generate immune responses and target antigenically variable pathogens and diseases, using synthetic peptides and nucleic acid sequences that encode variable amino acids to induce broad immune responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional vaccines use fixed epitopes, then they are simple to manufacture, but pathogens with genetic variability can mutate amino acids in epitopes to evade immune recognition
Solution Approach 1:
The vaccine composition transitions from static fixed epitopes to dynamic variable epitope libraries that can adapt to pathogen mutations. The VEL contains multiple epitope variants with different amino acid sequences, allowing the immune system to recognize both original and mutated pathogen strains, thus resolving the contradiction between reliable immune recognition and adaptability to mutations.
Solution Approach 2:
The invention changes the parameter of epitope sequence variability by incorporating epitopes with varying amino acid compositions. The VEL includes epitopes with different degrees of sequence identity to the wild-type, creating a spectrum of variants that can match diverse pathogen strains, thereby maintaining immune recognition effectiveness while adapting to genetic variability.
2Adaptability or versatility
If variable epitope libraries include multiple mutated epitope variants, then they can target antigenically variable pathogens, but the complexity of vaccine composition increases
Solution Approach 1:
The variable epitope library is segmented into distinct epitope variants, each with specific amino acid sequences and identity percentages. This segmentation allows systematic organization of complexity, where epitopes are grouped by their sequence characteristics (e.g., 50-70% identity, 30-50% identity, 10-30% identity), making the complex composition manageable and rational.
Solution Approach 2:
The VEL serves multiple functions simultaneously: it provides immune recognition for wild-type pathogens, mutated variants, and diverse strains within a single vaccine composition. The epitope variants collectively perform the work of multiple separate vaccines, reducing the need for multiple individual vaccine formulations while maintaining adaptability.
3Reliability
If epitopes undergo amino acid substitutions to escape immune recognition, then pathogen survival increases, but the ability to maintain functional epitope structure decreases
Solution Approach 1:
The epitope variants are designed with localized amino acid substitutions at specific positions while maintaining conserved regions. This local quality approach allows the pathogen to survive by mutating specific residues needed for immune escape, while the overall epitope structure and critical functional regions remain stable and recognizable by the immune system.
Solution Approach 2:
The vaccine incorporates epitope variants that anticipate potential mutation pathways. By including pre-designed variants with predicted amino acid substitutions, the vaccine cushions against future immune escape events, maintaining structural integrity requirements while accounting for survival-driven mutations.
Data Source
AI summary
The present disclosure relates to compositions and methods for targeting antigenically variable pathogens and diseases. Embodiments of the present disclosure involve of the construction of variable epitope libraries (VELs) containing mutated versions of epitopes derived from antigens associated with various diseases for treating subjects in both therapeutic and prophylactic settings. The present disclosure also provides compositions and methods for the production of VELs based on CTL-derived epitopes of survivin, an oncogenic inhibitor-of-apoptosis. Given the large number of potential epitopes expressed in tumors, and the dynamic nature of the tumor epitope landscape, there is a need to develop compositions and methods for targeting various antigenic epitopes to counteract immune escape.