Peptide Epitope Deletion for NKT Cell Immune Avoidance
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Solution Overview
Problem
Current therapeutic agents, viral vectors for gene therapy, and allergens often elicit immune responses, leading to reduced efficacy and increased side effects due to activation of natural killer T (NKT) cells, which recognize antigens presented by the CD1d molecule, resulting in unwanted immune reactions and inflammation.
Innovation Solution
Development of peptides or polypeptides modified to eliminate hydrophobic amino acid residues involved in CD1d binding epitopes, preventing activation of NKT cells by altering the amino acid sequence to disrupt binding to the CD1d molecule, thereby reducing immunogenicity and inflammatory responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If peptides or polypeptides are used as therapeutic agents, then therapeutic effect is achieved, but immune response is elicited leading to reduced efficacy
Solution Approach 1:
The patent extracts and removes hydrophobic amino acid residues from peptide sequences that are responsible for binding to CD1d molecules and activating NKT cells. By identifying and eliminating these specific hydrophobic residues (such as phenylalanine, tryptophan, tyrosine, leucine, isoleucine, and methionine at key positions), the therapeutic peptide retains its biological function while losing the ability to trigger unwanted immune responses.
Solution Approach 2:
The patent modifies the chemical parameters of peptides by substituting or deleting hydrophobic amino acid residues with hydrophilic or polar residues. This parameter change alters the peptide's binding affinity to CD1d molecules, thereby changing the immune response profile from immunogenic to tolerogenic or non-immunogenic, while preserving therapeutic activity.
2Productivity
If viral vectors are used for gene therapy, then gene delivery is achieved, but immune response eliminates transduced cells
Solution Approach 1:
The patent removes hydrophobic amino acid residues from viral vector proteins (such as adenovirus capsid proteins) that are responsible for NKT cell activation. By eliminating these hydrophobic epitopes, the viral vector maintains its gene delivery capability while avoiding activation of the adaptive immune response that would otherwise eliminate transduced cells and terminate transgene expression.
Solution Approach 2:
The patent applies preliminary modification to viral vectors by deleting hydrophobic residues before administration. This preemptive action prevents the formation of immunogenic epitopes that would trigger NKT cell activation and subsequent immune-mediated elimination of transduced cells, thereby ensuring prolonged transgene expression.
3Reliability
If allergens are used for vaccination, then immune response is elicited, but inflammatory side effects occur
Solution Approach 1:
The patent extracts and removes hydrophobic amino acid residues from allergen proteins that serve as epitopes for NKT cell recognition. By eliminating these hydrophobic sequences, the allergen retains its ability to induce protective immune responses against the underlying condition while losing the capacity to trigger proinflammatory NKT cell activation and associated side effects.
Solution Approach 2:
The patent modifies the immunological parameters of allergens by deleting hydrophobic residues, thereby changing the balance between protective immunity and inflammatory response. This parameter modification allows the allergen to function as a safe vaccine that induces tolerance or protective immunity without causing adverse inflammatory reactions.
4Reliability
If higher doses of vaccines are administered, then vaccine efficacy is improved, but proinflammatory side effects increase
Solution Approach 1:
The patent removes hydrophobic amino acid residues from vaccine antigens that are responsible for activating NKT cells and inducing proinflammatory responses. By eliminating these hydrophobic epitopes, higher doses of the vaccine can be administered to improve immunogenicity and efficacy without triggering unwanted inflammatory side effects, as the modified antigen no longer activates the NKT cell pathway.
Data Source
AI summary
The invention describes a method and compounds for the prevention of immune responses towards allofactors, towards viral vectors used for gene therapy and gene vaccination, towards proteins to which subjects are naturally exposed, towards genetically-modified organisms and towards undesirable effects related to vaccine administration for allergic or infectious diseases.