Liquid Vaccine Stabilization via Natural Deep-Eutectic Solvents
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Solution Overview
Problem
Existing vaccine production methods, particularly for live attenuated viruses, face challenges in maintaining viability during production, storage, and shelf-life, especially for sensitive enveloped viruses, which often require expensive and labor-intensive freeze-drying processes.
Innovation Solution
The development of a liquid vaccine composition using natural deep-eutectic solvents (NADES) with a water activity below 0.8, which stabilizes enveloped viruses without the need for freeze-drying, allowing for stable storage and administration at ambient temperatures.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If freeze-drying is used to preserve live attenuated viruses, then virus viability is maintained during storage, but the process becomes laborious, expensive, and time-consuming
Solution Approach 1:
The invention extracts and eliminates the freeze-drying step from the vaccine manufacturing process by using alternative stabilizing agents that allow live viruses to be stored in liquid form, thereby removing the complex and time-consuming freeze-drying equipment and procedures while maintaining virus viability
Solution Approach 2:
The invention changes the physical-chemical parameters of the storage environment by using specific stabilizing agents (such as sugars, amino acids, or proteins) that create optimal conditions for virus stability in liquid form, allowing storage at higher temperatures without freeze-drying
2Reliability
If liquid nitrogen storage is used for sensitive viruses, then virus stability is maintained, but the cost and labor requirements increase significantly
Solution Approach 1:
The invention changes the storage temperature parameter from extreme cold (liquid nitrogen at -196°C) to refrigerated temperatures (2-8°C) by using stabilizing agents that protect virus integrity at higher temperatures, thereby eliminating the need for expensive liquid nitrogen storage infrastructure
3Reliability
If aqueous compositions with sugar additives are used for liquid vaccines, then virus stability is improved, but the compositions do not provide sufficient longevity for sensitive viruses
Solution Approach 1:
The invention uses composite stabilizing formulations combining multiple agents (sugars, amino acids, proteins, and other excipients) that work synergistically to provide enhanced and prolonged protection for sensitive enveloped viruses, extending shelf-life beyond what single agents can achieve
Solution Approach 2:
The invention mimics the natural protective environment found in viral hosts by using biomimetic stabilizing agents that replicate the molecular chaperones and protective proteins naturally present in living systems, thereby extending virus survival in liquid form
4Reliability
If traditional solvents are used in vaccine formulations, then virus stability may be achieved, but the solvents are aggressive and may damage viral envelopes
Solution Approach 1:
The invention replaces aggressive traditional solvents with gentle, biocompatible stabilizing agents such as sugars, amino acids, and proteins that are non-denaturing and do not damage viral envelopes, using substances that are inherently safe for live virus formulations
Solution Approach 2:
The invention introduces stabilizing agents as intermediary substances that mediate between the virus and the aqueous environment, protecting the viral envelope from direct exposure to harmful conditions while maintaining virus stability and infectivity
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
This approach provides stable and cost-effective liquid vaccines for sensitive viruses, maintaining viral titers for extended periods and facilitating easier administration, while avoiding the aggressive nature of traditional solvents that might damage viral envelopes.
Implementation Method 1
The liquid vaccine composition has a water activity of less than about 0.8
Data Source
AI summary
The present invention describes a liquid vaccine composition of a live enveloped virus and a pharmaceutically acceptable carrier, whereby the carrier is a natural deep-eutectic solvent (NADES), and the vaccine has a water activity of less than about 0.8. The NADES provides a stabilisation of the sensitive virus for prolonged time and at ambient temperature. In general, the liquid vaccine compositions according to the invention, in different compositions for the various enveloped viruses, show remarkable capabilities of stabilisation. This overcomes the need for lyophilisation, a great economic benefit. Also the liquid nature of the vaccines facilitates administration to human or animal targets.