Dengue Vaccine Formulation Stabilization
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing dengue vaccine formulations face challenges in maintaining the stability and integrity of live attenuated dengue viruses during manufacturing, storage, transport, and lyophilization, leading to potential degradation and increased consumption, while also requiring improvements in lyophilization time and reconstitution compatibility.
Innovation Solution
A dengue vaccine formulation comprising a tetravalent dengue virus composition with live attenuated dengue virus serotypes 1 to 4, combined with excipients like trehalose, poloxamer, urea, arginine hydrochloride, tromethamine, and human serum albumin, enhances stability and reduces degradation during manufacturing, storage, and transport, and improves lyophilization efficiency and reconstitution compatibility.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If live attenuated dengue virus is used in vaccine formulation, then potent and long-lasting immune responses are generated, but the virus degrades during manufacturing, storage and transport
Solution Approach 1:
The patent introduces excipients (stabilizers, buffers, and protective agents) as intermediary substances that mediate between the live attenuated virus and the external environment. These excipients form a protective matrix around the virus particles, shielding them from degradation during manufacturing, storage, and transport while allowing the virus to maintain its immunogenicity and replicate effectively after vaccination.
Solution Approach 2:
The patent optimizes formulation parameters including pH, ionic strength, and excipient concentrations to create a stable environment for the live attenuated virus. By carefully controlling these physical and chemical parameters, the formulation maintains virus stability without compromising the virus's ability to replicate and induce immune responses after administration.
2Reliability
If virus concentration is increased to ensure end of shelf life potency, then vaccine effectiveness is maintained, but manufacturing cost and complexity increase
Solution Approach 1:
The patent incorporates stabilizing excipients in the initial formulation that proactively protect the virus throughout the shelf life period. This preliminary protective action prevents virus degradation over time, ensuring that the required potency is maintained at the end of shelf life without needing to over-concentrate the virus or implement complex manufacturing controls.
3Stability of the object's composition
If lyophilization is used to improve virus stability, then storage and transport conditions are improved, but drying time and process complexity increase
Solution Approach 1:
The patent modifies formulation parameters including the addition of lyoprotectants and optimization of freezing protocols to enable faster and more effective lyophilization. These parameter changes allow the virus to be stabilized through freeze-drying with reduced drying times and improved final stability, balancing process efficiency with virus protection.
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 formulation maintains the immunizing capacity of the live attenuated dengue viruses, reduces degradation, and ensures effective reconstitution with minimal foaming, providing a stable and efficient vaccine solution for diverse populations and environments.
Implementation Method 1
A dengue vaccine formulation comprising a tetravalent dengue virus composition with live attenuated dengue virus serotypes 1 to 4, combined with excipients like trehalose, poloxamer, urea, arginine hydrochloride, tromethamine, and human serum albumin, enhances stability and reduces degradation during manufacturing, storage, and transport
Implementation Method 2
improves lyophilization efficiency and reconstitution compatibility
Data Source
Figure 1
Figure 2
Figure 3
AI summary
The present invention relates to a dengue vaccine formulation comprising a tetravalent dengue virus composition comprising a live attenuated dengue virus serotype 1, a live attenuated dengue virus serotype 2, a live attenuated dengue virus serotype 3, and a live attenuated dengue virus serotype 4, at least one non-reducing disaccharide, at least one poloxamer, urea, at least one amino acid having a positively charged side chain at neutral pH, tromethamine, and human serum albumin.