Polypeptide Vaccine Multi-Epitope HLA Coverage
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Solution Overview
Problem
Current vaccine development for SARS-CoV-2 faces challenges in addressing the variability of immune responses among individuals and the potential heterogeneity of the virus, with existing approaches often resulting in lower immune response rates and limited global population coverage.
Innovation Solution
Development of polypeptide vaccines comprising specific amino acid sequences (SEQ ID NOs: 1 to 17) that induce CD8+, CD4+, and antibody-producing B-cell responses, targeting multi-HLA binding epitopes to maximize population coverage and robustness against viral mutations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional vaccine approaches are used, then vaccine development is simpler and faster, but immune response rates are lower and population coverage is limited
Solution Approach 1:
The vaccine divides the antigen into multiple distinct polypeptide components (at least two different polypeptides), each targeting specific epitopes. This segmentation allows the vaccine to address multiple viral variants and HLA types simultaneously, improving immune response rates across diverse populations while managing complexity through modular design
Solution Approach 2:
The vaccine employs a composite structure combining multiple polypeptide sequences with different functionalities (CD8+ T cell epitopes, CD4+ T cell epitopes, and B cell epitopes) along with adjuvants and carriers. This composite approach enhances overall immunogenicity and population coverage by engaging multiple immune pathways simultaneously
2Adaptability or versatility
If single-epitope vaccines are used, then vaccine formulation is simpler, but coverage of global population is limited
Solution Approach 1:
The vaccine incorporates epitopes that bind to multiple HLA class I and class II alleles across different human populations. By selecting polypeptides with broad HLA binding specificity, the vaccine achieves universal applicability across diverse genetic backgrounds, covering over 99% of the global population without requiring separate formulations for different ethnic groups
Solution Approach 2:
The vaccine includes polypeptides with different functional properties: some optimized for CD8+ T cell activation, others for CD4+ T cell help, and additional ones for B cell antibody production. This local differentiation of polypeptide functions within the composite vaccine enhances overall population coverage by addressing diverse immune response patterns
3Adaptability or versatility
If vaccines target single HLA alleles, then epitope selection is easier, but coverage of HLA diversity is insufficient
Solution Approach 1:
The vaccine includes polypeptides that bind to more HLA alleles than the minimum required for adequate coverage. By incorporating epitopes with excessive HLA binding capability (binding to 5+ or even 10+ different alleles), the vaccine ensures robust coverage across HLA diversity while simplifying the selection process through prioritization of highly promiscuous epitopes
4Reliability
If vaccines are designed for specific viral strains, then development is more focused, but resilience to viral mutations is reduced
Solution Approach 1:
The vaccine incorporates polypeptide sequences from multiple viral strains and variants, not just a single strain. By changing the parameter of sequence diversity to include conserved epitopes across different coronaviruses (SARS-CoV, MERS-CoV, SARS-CoV-2 variants), the vaccine achieves resilience to viral mutations while managing complexity through selection of evolutionarily conserved regions
Data Source
AI summary
The disclosure relates to polypeptides, vaccines and pharmaceutical compositions that find use in the prevention or treatment of Coronaviridae or SARS-CoV-2 infection. The disclosure also relates to methods of treating or preventing Coronaviridae or SARS-CoV-2 infection in an individual. The polypeptides and vaccines comprise T cell and/or B cell epitopes that are immunogenic in a high percentage of individuals in the human population.