Spike Protein Nanoparticles With Detergent Core for Vaccine Stability
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Developing vaccines against highly sophisticated pathogens like SARS-CoV-2 is challenging due to their evasion mechanisms and the need for stability in various environments without refrigeration, while inducing antibodies that block or neutralize infectious agents.
Innovation Solution
Non-naturally occurring CoV S polypeptides, particularly BV2373, are engineered with modifications such as an inactive furin cleavage site, fusion peptide deletion, and K986P and V987P mutations, formulated into nanoparticles with a detergent core to enhance stability and epitope presentation, and optionally combined with adjuvant MATRIX-M™ to stimulate robust immune responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional vaccine approaches are used, then vaccine development can proceed with standard formulations, but the vaccines fail to remain stable in environments without refrigeration and cannot effectively counter pathogen evasion mechanisms
Solution Approach 1:
The patent modifies physical and chemical parameters of the vaccine formulation by incorporating specific excipients (sugars, amino acids, buffers) that change the stability parameters of the antigen, enabling the vaccine to maintain potency across a broader temperature range without requiring refrigeration
Solution Approach 2:
The patent creates a composite vaccine formulation by combining the coronavirus antigen with multiple stabilizing excipients (sugars like sucrose and trehalose, amino acids like arginine and proline, buffers, and surfactants) to achieve enhanced environmental stability while maintaining immunogenicity
2Reliability
If vaccine formulations are designed to induce strong immune responses, then neutralizing antibodies are produced, but the formulations become less stable in various environments
Solution Approach 1:
The patent optimizes the concentration parameters of excipients in the formulation - using specific ranges of sugars (1-50 mM), amino acids (1-50 mM), and buffers to achieve the optimal balance between maintaining antigen stability and preserving immunogenicity for inducing neutralizing antibodies
Solution Approach 2:
The patent introduces excipients as intermediary substances that mediate between the antigen and the environment - these excipients form protective complexes with the antigen, shielding it from environmental stressors while allowing the antigen to maintain its immunogenic properties for inducing strong immune responses
Data Source
AI summary
Disclosed herein are coronavirus Spike (S) proteins and nanoparticles comprising the same, which are suitable for use in vaccines. The nanoparticles present antigens from pathogens surrounded to and associated with a detergent core resulting in enhanced stability and good immunogenicity. Dosages, formulations, and methods for preparing the vaccines and nanoparticles are also disclosed.