Influenza Vaccine Antigen Splitting for Higher Yield Purification
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Solution Overview
Problem
Existing methods for preparing influenza vaccines, particularly split and surface antigen vaccines, face inefficiencies in antigen yield and purification, especially with strains like H5 subtype influenza A virus.
Innovation Solution
Modifying the timing and order of detergent use, increasing ionic strength of buffers, using cellulose membranes for ultrafiltration, and introducing a diafiltration step before capture, along with detergent exchange and phosphate buffers, to enhance antigen yield and purification.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If detergent is used prior to virus inactivation, then antigen solubility is facilitated, but antigen yield is reduced
Solution Approach 1:
The patent applies preliminary action by performing virus inactivation before detergent treatment. The virus is inactivated first using beta-propiolactone or formaldehyde, and only after inactivation is complete does the process introduce detergent for splitting. This reversal of the conventional sequence ensures that detergent does not interfere with inactivation efficiency while still achieving adequate antigen solubility and yield.
2Quantity of substance
If conventional splitting procedures are used, then virus disruption is achieved, but antigen yield remains low
Solution Approach 1:
The patent applies parameter changes by optimizing the detergent concentration and composition used for virus splitting. Specifically, it employs non-ionic detergents at controlled concentrations (0.1-1% v/v) after inactivation, which improves antigen release efficiency. Additionally, the use of phosphate buffers at specific pH ranges (6.5-8.5) and ionic strengths enhances antigen stability and yield during the splitting process, directly addressing the low antigen yield problem.
3Quantity of substance
If multiple detergents are used in sequence, then virus splitting is improved, but process complexity increases
Solution Approach 1:
The patent applies the extraction principle by removing the first detergent treatment step that occurs before inactivation in conventional processes. By eliminating this preliminary detergent exposure and performing inactivation first, the process simplifies the overall workflow while maintaining or improving antigen yield. The single post-inactivation detergent treatment is sufficient for effective virus splitting without the complexity of multiple sequential detergent treatments.
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
These modifications result in a >20-fold increase in antigen yield, particularly for H5 subtype influenza A virus, improving the efficiency and effectiveness of vaccine preparation processes.
Implementation Method 1
influenza virions are exposed to a first detergent (e.g. a polysorbate, such as polysorbate 80) prior to splitting by a second detergent (e.g. CTAB)
Implementation Method 2
inactivating the influenza virions in the absence of detergent
Data Source
AI summary
A number of improvements for preparing vaccine antigens from disintegrated influenza viruses are disclosed. A splitting step can be followed by detergent exchange. Splitting can take place in the presence of a buffer with a higher ionic strength and/or in the presence of phosphate buffer.