Non-ionic Isotonicity Agents in Liposomal Adjuvants
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Solution Overview
Problem
Certain antigens are sensitive to 'salting out' at low sodium chloride concentrations, leading to protein aggregation and precipitation, which complicates the formulation and reconstitution of vaccine compositions, as existing adjuvant compositions with higher salt concentrations are not suitable for these antigens.
Innovation Solution
Development of aqueous adjuvant compositions with a Toll-like receptor 4 agonist and saponin in a liposomal formulation, using a non-ionic isotonicity agent such as sorbitol to maintain low sodium chloride concentrations below 100mM, thereby preventing antigen precipitation and ensuring immunogenicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If sodium chloride is used as an isotonicity agent in adjuvant compositions, then the composition achieves physiological isotonicity, but sensitive antigens aggregate and precipitate at concentrations above 100mM
Solution Approach 1:
The patent replaces sodium chloride with non-ionic isotonicity agents (sucrose, sorbitol, mannitol, glycerol) to change the chemical nature of the isotonicity agent while maintaining the physiological tonicity of the composition. This parameter change allows achieving isotonicity without the harmful salting-out effect on sensitive antigens
Solution Approach 2:
Non-ionic isotonicity agents serve as intermediary substances that perform the function of maintaining isotonicity without directly interacting with antigens to cause aggregation. These agents mediate the isotonicity requirement while preserving antigen solubility and stability
2Productivity
If existing adjuvant compositions with higher salt concentrations are used, then the adjuvant provides strong immune stimulation, but the formulation becomes unsuitable for sensitive antigens due to precipitation
Solution Approach 1:
The patent creates adjuvant compositions with non-ionic isotonicity agents that are universally compatible with both salt-sensitive and salt-tolerant antigens. This multi-functional formulation can be used across a broader range of antigen types without requiring separate formulations for sensitive versus tolerant antigens
3Ease of operation
If lyophilised antigens are reconstituted with traditional adjuvant preparations containing buffer and salt, then the reconstitution process is straightforward, but the antigen may lose immunogenicity or solubility due to incompatible buffer conditions
Solution Approach 1:
The patent modifies the buffer composition parameters by replacing ionic isotonicity agents with non-ionic alternatives, creating reconstitution solutions that maintain antigen solubility and immunogenicity while simplifying the reconstitution process for lyophilised formulations
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 use of low sodium chloride concentrations in combination with a non-ionic isotonicity agent like sorbitol allows for the formulation of immunogenic compositions that maintain antigen solubility and immunogenicity, effectively preventing 'salting out' and enhancing the immune response, as demonstrated by improved humoral and cellular responses in mouse models.
Implementation Method 1
some antigens are particularly sensitive to a phenomenon known as 'salting out' which may be defined as the precipitation of a protein from its solution by saturation with a salt such as sodium chloride
Data Source
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AI summary
Adjuvant and immunogenic compositions comprising a TLR-4 agonist and a saponin in a liposomal formulation, and a non-ionic isotonicity agent are provided, wherein the concentration of sodium chloride or ionic strength is less than 100mM.