Mannitol Stabilization for MVA Viral Vaccine Storage
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Solution Overview
Problem
Viruses used in vaccines are unstable at temperatures below freezing, leading to physical disruption and loss of infectivity during freezing and thawing, and existing stabilizers like human serum albumin can cause anaphylactic responses and complicate removal of viral contamination.
Innovation Solution
Mannitol is used as a sole stabilization agent in liquid and liquid-frozen viral vaccine compositions, providing cryoprotection and free-radical scavenging properties to maintain virus titer stability across various temperatures, including above and below freezing, and during storage for extended periods.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of stationary object
If viruses are stored frozen to maintain stability, then storage duration is extended, but physical disruption occurs during freezing and thawing leading to loss of infectivity
Solution Approach 1:
Mannitol acts as an intermediary substance between the virus and the freezing environment. It forms a protective matrix that mediates the freezing process, preventing direct physical disruption to viral structures while allowing frozen storage for extended periods without loss of infectivity
Solution Approach 2:
The invention changes the physical-chemical parameters of the storage environment by introducing mannitol, which alters the freezing behavior of the solution. This includes changing the freezing point, reducing ice crystal formation, and modifying the glass transition temperature, thereby protecting virus infectivity during frozen storage
2Stability of the object's composition
If human serum albumin is used as a stabilizer, then virus stability is improved, but anaphylactic responses occur and viral contamination removal becomes complicated
Solution Approach 1:
Mannitol replaces human serum albumin as a stabilizer. While mannitol is a simple, inexpensive substance, it provides sufficient stabilization for the required storage period without the harmful immunogenic properties of albumin, effectively serving as a disposable, safe alternative
Solution Approach 2:
The invention extracts and eliminates the harmful immunogenic components (human serum albumin) from the formulation while retaining the essential stabilization function through mannitol, thereby removing the source of anaphylactic responses
3Duration of action of stationary object
If viruses are stored at temperatures below freezing, then storage shelf life is extended, but physical disruption of structural components occurs
Solution Approach 1:
Mannitol provides beforehand cushioning by forming a protective glassy matrix around viral structures before freezing occurs. This pre-formed protective environment cushions against mechanical stresses during freezing and thawing, preventing structural disruption while enabling long-term frozen storage
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
Mannitol maintains at least 20% of the original virus titer for up to 5 years, offering enhanced stability and reducing the need for complex removal processes, while avoiding adverse reactions associated with other stabilizers.
Implementation Method 1
Mannitol is used as a sole stabilization agent in liquid and liquid-frozen viral vaccine compositions, providing cryoprotection... to maintain virus titer stability across various temperatures, including above and below freezing
Implementation Method 2
providing cryoprotection and free-radical scavenging properties to maintain virus titer stability
Data Source
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AI summary
A liquid or liquid-frozen composition comprising: a modified vaccinia Ankara (MVA) virus or variant or derivative thereof and mannitol, wherein mannitol is the sole stabilization agent of the composition. The mannitol may provide a stabilizing effect at 0 to +100C or in a liquid-frozen composition, for example between -100C and -300C or between -200C and -23.50C. The MVA may be used as a vaccine or for use in gene therapy, virotherapy, immunotherapy, or cancer therapy in a mammal, preferably a human.