pH-Sensitive Carrier for CTL Induction in Vaccine Adjuvants

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Solution Overview

Problem

Current methods for inducing cytotoxic T lymphocytes (CTL) for cell-mediated immunity in vaccine development are not satisfactory, often relying on unsafe synthetic materials or virus-derived components, and there is a need for a safe and effective carrier that can induce CTL through cross-presentation.

Innovation Solution

A pH-sensitive carrier composition combining specific pH-sensitive compounds and amphipathic substances, along with a substance to activate the innate immune system, such as monophosphoryl lipid A, is used to effectively induce CTL by facilitating antigen transport into the cytosol, thereby enhancing CTL induction.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If synthetic materials or virus-derived components are used to induce CTL, then CTL induction effect is improved, but safety is worsened

Engineering Contradiction:
ImproveCTL induction effectVSAvoidsafety
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent uses a pH-sensitive carrier as an intermediary substance that facilitates antigen transport into the cytosol without directly acting as the antigen or requiring synthetic materials. The carrier mediates the cross-presentation process by enabling endogenous antigen expression, thereby achieving CTL induction through a safe, natural mechanism rather than through potentially harmful synthetic or virus-derived components

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent exploits pH-sensitive changes in the carrier to control antigen release and transport. The carrier's pH-sensitive properties allow it to change conformation or release cargo in response to pH changes within endosomes or lysosomes, enabling controlled antigen delivery to the cytosol for MHC Class I presentation without requiring unsafe adjuvants

Inventive Principle:
Principle #35Parameter changes

2Productivity

If cross-presentation is used to induce CTL, then cell-mediated immunity is improved, but membrane disruption safety is worsened

Engineering Contradiction:
ImproveCTL inductionVSAvoidmembrane disruption safety
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The pH-sensitive carrier utilizes the cell's own pH gradient and endocytic machinery to achieve antigen transport. The carrier passesively exploits the natural pH environment within endosomes to trigger its membrane-disrupting function, allowing the cell to serve itself in the process without external intervention or harmful substances

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The patent employs a composite structure combining pH-sensitive compounds with amphipathic substances to create a carrier system that safely facilitates membrane disruption. This composite approach ensures controlled and localized membrane permeabilization only where needed for antigen delivery, avoiding widespread or unsafe membrane disruption

Inventive Principle:
Principle #40Composite materials

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 described adjuvant composition safely and effectively induces CTL by promoting membrane disruption and fusion, leading to enhanced CTL induction and immune response, while being free from the safety concerns associated with synthetic or virus-derived components.

Implementation Method 1

A pH-sensitive carrier composition combining specific pH-sensitive compounds and amphipathic substances, along with a substance to activate the innate immune system, such as monophosphoryl lipid A, is used to effectively induce CTL by facilitating antigen transport into the cytosol

Methodology Applied
Scientific EffectpH-sensitive carrier mechanism:

Implementation Method 2

The described adjuvant composition safely and effectively induces CTL by promoting membrane disruption and fusion

Methodology Applied
Scientific EffectMembrane disruption:

Data Source

PatentUS11000586B2Adjuvant composition, vaccine composition containing the same, and method for producing both of them
Publication Date: 2021.05.11 TERUMO KK
  • US11000586B2 patent drawing
  • US11000586B2 patent drawing
  • US11000586B2 patent drawing

AI summary

An adjuvant composition includes a pH-sensitive carrier and a substance with stimulus to activate innate immune system. The adjuvant composition serves as a carrier which is highly safe and capable of efficient induction of CTL.