ISCOM Mixture Segmentation for Vaccine Toxicity Reduction
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Solution Overview
Problem
Quillaja saponin preparations used in vaccines often cause toxicity and side effects due to their heterogeneous nature, limiting their effective use in immunizations, as different fractions exhibit varying toxicity and immunomodulating properties, making it challenging to achieve optimal immunogenicity and tolerability.
Innovation Solution
The use of separate iscom or iscom-matrix complexes comprising different purified fractions of Quillaja saponaria Molina, where each fraction is incorporated into distinct particles rather than combined within the same particle, allowing for a mixture of these particles to create vaccine formulations that are less toxic and easier to tailor for enhanced immunogenicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If purified fractions of Quillaja saponin are used in vaccine formulations, then immunogenicity is improved, but toxicity and side effects increase
Solution Approach 1:
The patent divides the Quillaja saponin mixture into separate purified fractions (A, B, and C) and incorporates each fraction into distinct ISCOM or ISCOM-matrix particles. This segmentation allows the immune system to be stimulated by multiple fractions simultaneously, improving immunogenicity while distributing the toxic load across separate particles rather than concentrating it in a single formulation
Solution Approach 2:
Different fractions of Quillaja saponin have different immunomodulating properties and toxicity levels. The patent assigns specific fractions to specific ISCOM or ISCOM-matrix particles based on their characteristics, creating particles with tailored local qualities. This allows optimization of each particle's immunogenicity-toxicity ratio while maintaining overall formulation effectiveness
2Ease of manufacture
If heterogeneous Quillaja saponin preparations are used, then manufacturing is simplified, but batch consistency and predicted adjuvant activity decrease
Solution Approach 1:
The patent segments the heterogeneous Quillaja saponin preparation into distinct purified fractions (A, B, and C) that can be independently characterized and controlled. Each fraction has defined properties and consistent behavior, enabling batch-to-batch reproducibility. The segmented approach transforms an unpredictable heterogeneous mixture into可控 homogeneous components that maintain manufacturing simplicity while achieving consistency
Solution Approach 2:
The patent changes the purity parameter of Quillaja saponin from heterogeneous to purified fractional forms. By defining specific purity levels and characteristics for each fraction (A, B, and C), the patent enables precise control over adjuvant activity while maintaining ease of manufacture through standardized purification and characterization protocols
Data Source
AI summary
The invention relates to a composition comprising a mixture of at least two iscom complexes each complex comprising essentially one saponin fraction from Quillaja Saponaria Molina. The complexes may be iscom complexes or iscom matrix complexes. The invention also pertains to the use of such a mixture for the preparation of an immunomodulating pharmaceutical, and adjuvant, formulations for immunization, e.g. for production of monoclonal antibodies, and a vaccine. Kits of parts comprising at least two parts, wherein each part comprises one iscom complex or one iscom matrix complex according to the invention are also embraced.