Peptide-Poly IC Complexes for T Cell Activation

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Solution Overview

Problem

Existing vaccine technologies fail to effectively deliver specific antigens to the immune system to activate antigen-specific T cells, leading to inadequate immune responses against pathogens and tumors.

Innovation Solution

Modifying synthetic peptides corresponding to CD8 and CD4 T cell epitopes by adding cationic amino acids, hydrophobic residues, or lipids to form complexes with immune adjuvants like polyinosinic:polycytidylic acid (Poly-IC), enhancing their immunogenicity and enabling efficient activation of antigen-specific T cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If peptides are used as vaccine antigens, then the vaccine can be recognized by the immune system and induce T cell responses, but the immune response is insufficient and fails to provide adequate protection

Engineering Contradiction:
Improveimmune response effectivenessVSAvoidpeptide structure complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent creates composite structures by conjugating peptides to carrier proteins (such as keyhole limpet hemocyanin or ferritin), forming peptide-carrier conjugates that combine the immunogenicity of the carrier with the specific antigenic properties of the peptide, thereby enhancing the overall immune response while maintaining a relatively simple preparation process

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The patent modifies peptide parameters by changing their chemical structure through conjugation with carrier proteins, altering properties such as molecular weight, stability, and immunogenicity to achieve better immune responses without significantly complicating the vaccine formulation

Inventive Principle:
Principle #35Parameter changes

2Reliability

If peptides are modified to enhance immunogenicity, then antigen-specific T cell activation is improved, but the complexity of peptide synthesis and formulation increases

Engineering Contradiction:
Improveantigen-specific T cell activationVSAvoidpeptide synthesis and formulation
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent uses carrier proteins as intermediaries that facilitate the interaction between peptides and the immune system. The carrier proteins act as adjuvants that enhance peptide uptake by antigen-presenting cells and promote T cell activation, thereby improving immunogenicity without requiring complex chemical modifications of the peptides themselves

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent performs preliminary conjugation of peptides to carrier proteins during the manufacturing process, creating pre-formulated peptide-carrier conjugates that are ready for immunization. This preliminary action simplifies subsequent formulation steps and ensures consistent immunogenicity across vaccine batches

Inventive Principle:
Principle #10Preliminary action

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 modified peptide-Poly-IC complexes induce robust and sustained immune responses, generating large numbers of antigen-specific CD8 T lymphocytes, making them effective as prophylactic or therapeutic vaccines against infectious diseases and malignant disorders.

Implementation Method 1

modifying synthetic peptides corresponding to CD8 and CD4 T cell epitopes by adding cationic amino acids, hydrophobic residues, or lipids to form complexes with immune adjuvants like polyinosinic:polycytidylic acid (Poly-IC)

Methodology Applied
Scientific EffectElectrostatic interaction: Electrostatics

Data Source

PatentUS10463747B2Method of developing a vaccine using peptide-poly IC complexes
Publication Date: 2019.11.05 H LEE MOFFITT CANCER CENTER & RESEARCH INSTITUTE INC
  • US10463747B2 patent drawing
  • US10463747B2 patent drawing
  • US10463747B2 patent drawing

AI summary

The invention describes the development of more potent peptide vaccines to prevent or treat infections or cancer and their administration to a subject in order to elicit a T cell response in the subject. Small synthetic peptides from the known sequences of viral, bacterial, parasitic or tumor antigens are modified so they can spontaneously form complexes with a synthetic nucleic acid, such as Poly IC, that functions as an immunological adjuvant. The peptide-nucleic acid complexes are dramatically more immunogenic as compared to the separate components. The procedure for developing the vaccine involves the conjugation of a synthetic peptide containing a C residue to poly-K using a bi-functional cross-linking reagent (SMCC). The peptide/poly-K complex was then formulated with CMC and poly-IC to produce a self-adjuvant vaccine that was 36-fold more effective as compared to the same peptide administered mixed with the same adjuvant (but not complexed to it).