Multi-MHC Polypeptide Vaccines for Broad HLA-DR Coverage
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Solution Overview
Problem
Existing polypeptide-based vaccines struggle to induce immune responses across diverse MHC molecules in a mammalian population, limiting their effectiveness in treating cancer and precancerous conditions.
Innovation Solution
Development of polypeptides ranging from 18 to 55 amino acids in length, specifically designed to bind to multiple MHC molecules, including HLA-DRB1 alleles, to induce broad immune responses, using algorithms like netMHCII-pan to identify promiscuous epitopes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If polypeptide-based vaccines use epitopes derived from target proteins to provoke immune reactions, then the ability to induce specific immune response is improved, but the ability to target a wide range of MHC molecules across different populations deteriorates due to genetic diversity in HLA-DR molecules
Solution Approach 1:
The vaccine composition is segmented into multiple polypeptide components, each designed to bind to different HLA-DR molecules. This segmentation allows the vaccine to cover a broader spectrum of MHC molecules across diverse populations while maintaining specific immune responses against each cancer-associated antigen.
Solution Approach 2:
The patent develops polypeptides with multi-functional binding capabilities, where each polypeptide can bind to multiple different HLA-DR molecules. This universality enables a single vaccine composition to effectively target a wide range of MHC molecules across different ethnic groups, resolving the contradiction between specificity and broad coverage.
2Adaptability or versatility
If polypeptides are designed to bind to multiple HLA-DR molecules to cover diverse populations, then the adaptability to different MHC molecules is improved, but the manufacturing complexity increases due to the need to identify and produce multiple polypeptide variants
Solution Approach 1:
The patent systematically varies key parameters of polypeptide sequences (amino acid composition, length, and binding affinity) to optimize binding to different HLA-DR molecules. By controlling these parameters during the design phase, multiple polypeptide variants can be produced with predictable binding characteristics, reducing manufacturing complexity while maintaining broad HLA-DR coverage.
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 designed polypeptides effectively induce immune responses in a wide range of MHC molecules, enabling vaccines to treat various cancers and precancerous conditions by activating and expanding T-cells, thus providing therapeutic benefits.
Implementation Method 1
polypeptides that can be processed into fragments binding to at least 85% of MHC molecules present in a mammalian population
Data Source
AI summary
This document provides methods and materials relating to isolated polypeptides, polypeptide preparations, vaccine preparations (e.g., anti-cancer vaccine preparations), and methods for vaccinating mammals. For example, polypeptides (e.g., CMV, MUC1, HER2, Mesothelin (MESO), TRAG-3, or CALR polypeptides) having the ability to be processed into different polypeptides such that the processed polypeptides as a group are capable of being presented by different MHC molecules present in a particular mammalian population are provided.