Conserved Peptide Block Identification for Vaccine Coverage
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Solution Overview
Problem
Current methods for developing vaccines against highly variable viral pathogens, such as dengue virus, exclude low-frequency antigenic peptides, leading to incomplete coverage and reduced vaccine effectiveness, as they focus on high-frequency conserved peptides, thereby neglecting the immunogenic potential of less frequent variants.
Innovation Solution
A novel method for identifying conserved peptide blocks in multiple sequence alignments that includes variant sequences, allowing for the identification of new target epitopes and the design of immunogenic peptide compositions that incorporate peptides binding to MHC molecules, thereby expanding the number of potential vaccine targets and improving coverage.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If traditional conservation analysis methods focusing on individual amino acid conservation are used, then high-frequency conserved peptides can be identified, but low-frequency antigenic peptides are excluded leading to incomplete vaccine coverage
Solution Approach 1:
The patent segments the polypeptide sequence into overlapping peptide blocks (e.g., 9-mers, 10-mers, 11-mers) and analyzes conservation at the block level rather than individual amino acid level. This segmentation allows low-frequency peptides to be identified as conserved blocks, expanding vaccine coverage while maintaining analytical precision.
Solution Approach 2:
The patent transitions from analyzing conservation along the single dimension of individual amino acid frequency to analyzing conservation in the dimensional space of peptide blocks. By evaluating blocks containing multiple amino acids, the method captures conserved epitopes that would be missed by single amino acid analysis, thereby improving vaccine coverage breadth.
2Stability of the object's composition
If only high-frequency conserved peptides are included in vaccine design, then conservation is maximized, but the number of identified targets is limited reducing vaccine effectiveness
Solution Approach 1:
The patent changes the conservation threshold parameter from requiring high individual amino acid frequency to accepting peptide blocks with lower overall frequency but high conservation within the block. This parameter change enables identification of additional conserved peptide blocks, increasing the quantity of vaccine targets while maintaining conservation stability.
3Device complexity
If low-frequency antigenic peptides are excluded from vaccine design, then vaccine composition simplicity is maintained, but coverage of viral variants is incomplete reducing protective efficacy
Solution Approach 1:
By segmenting the analysis into discrete peptide blocks with specific length ranges (9-11 amino acids), the patent creates a systematic framework for including low-frequency peptides. This segmentation approach maintains compositional organization and simplicity while expanding variant coverage, thereby improving protective efficacy without excessive complexity.
Data Source
AI summary
Methods for identifying at least one conserved peptide block in three or more homologous polypeptides are provided and compositions comprising conserved peptides are provided. More particularly, methods for selecting conserved peptides in variable viral polypeptides for use in immunogenic compositions are provided.