TCR-Enriched Clonotypes for Targeted 2019-nCoV Vaccine Development
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Solution Overview
Problem
The rapid spread of the 2019-novel coronavirus (2019-nCoV) poses a significant threat to global health, with no effective vaccine available, and current treatments focus on symptomatic relief rather than addressing the underlying infection, highlighting the urgent need for vaccine development.
Innovation Solution
The disclosure provides TCR-enriched clonotypes, specifically amino acid sequences and a method for acquiring them through TCR/BCR V(D)J immune repertoire sequencing analysis from cured patients, which can guide vaccine development by identifying shared CDR3 variable regions that recognize antigenic epitopes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If conventional symptomatic treatment is used, then patient comfort is improved, but the underlying viral infection is not addressed and disease progression continues
Solution Approach 1:
The patent extracts and identifies specific TCR clonotypes from cured patients that are associated with viral clearance. By isolating these specific immune receptor sequences, the invention enables targeted vaccine development that focuses on the specific antigenic epitopes recognized by these protective T cells, thereby addressing the underlying infection mechanism rather than just providing symptomatic relief
Solution Approach 2:
The patent performs preliminary sequencing and analysis of TCR repertoires from cured patients to identify protective clonotypes before vaccine deployment. This preliminary action allows the vaccine to be designed in advance with the specific antigenic epitopes that trigger these protective T cell responses, ensuring the vaccine prepares the immune system for effective viral clearance before infection occurs
2Reliability
If vaccine development is pursued, then effective prevention is improved, but development time and resource investment increase
Solution Approach 1:
The patent performs preliminary sequencing and analysis of TCR repertoires from cured patients to identify protective clonotypes before vaccine deployment. This preliminary action allows the vaccine to be designed in advance with the specific antigenic epitopes that trigger these protective T cell responses, ensuring the vaccine prepares the immune system for effective viral clearance before infection occurs
Solution Approach 2:
The patent uses TCR sequences from cured patients as templates to design vaccine epitopes. By copying the specific antigen recognition patterns from successfully infected and recovered individuals, the invention creates a vaccine that replicates the protective immune response without requiring lengthy trial-and-error development processes
3Measurement precision
If TCR sequencing analysis is performed, then identification of shared CDR3 regions is improved, but complexity of the analysis process increases
Solution Approach 1:
The patent extracts and focuses analysis on the CDR3 region, which is the most variable and antigen-specific portion of the TCR. By isolating this specific region for sequencing and analysis, the invention simplifies the complex TCR sequencing data into actionable insights about antigen recognition, making the analysis more manageable while maintaining high precision in identifying protective clonotypes
Solution Approach 2:
The patent applies local quality analysis by focusing specifically on the CDR3 region's sequence characteristics, conservation patterns, and epitope binding properties. This localized analysis approach allows for precise identification of shared regions while avoiding the computational complexity of analyzing the entire TCR structure, thereby improving measurement precision without proportionally increasing analysis complexity
Data Source
AI summary
Disclosed are TCR-enriched clonotypes, and an acquisition method and use thereof. Amino acid sequences of the TCR-enriched clonotypes are: CAANRGSGYSTLTF (SEQ ID NO: 1)_CSARGERGEKLFF (SEQ ID NO: 2), CASSSGGSYIPTF (SEQ ID NO: 3)_CASSLAGGHETQYF (SEQ ID NO: 4), CAVNSYNTDKLIF (SEQ ID NO: 5)_CATSREEDNTYEQYF (SEQ ID NO: 6), CAVGGNEKLTF (SEQ ID NO: 7)_CASSQGTGRSSPLHF (SEQ ID NO: 8), or CAASAVGGAQKLVF (SEQ ID NO: 9)_CATSRGTLYGYTF (SEQ ID NO: 10), respectively. The TCR-enriched clonotypes can be used for vaccine development.