Tocopherol Squalene Emulsion Adjuvant Stabilizing Prefusion S Protein
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
There is an urgent need for efficacious vaccines to combat the ongoing COVID-19 pandemic, particularly in developing countries, where variants of SARS-COV-2 continue to emerge, and existing vaccines may not provide adequate protection against severe illness and mortality, especially in individuals with comorbidities.
Innovation Solution
The development of an immunogenic composition comprising recombinant SARS-COV-2 S proteins, expressed in a baculoviral/insect cell system, stabilized in the prefusion conformation, combined with a tocopherol-containing squalene emulsion adjuvant, to enhance immune response and provide protection against COVID-19.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If recombinant SARS-COV-2 S proteins are used as vaccine antigen, then immune response is elicited, but the proteins may not remain stable in prefusion conformation
Solution Approach 1:
The patent applies parameter changes by modifying the S protein sequence at specific positions (e.g., introducing proline residues at positions 988-989 and glycine at position 687) to alter the biophysical properties of the protein, thereby stabilizing it in the prefusion conformation. This sequence modification changes the energy landscape of the protein to favor the stable prefusion state.
Solution Approach 2:
The patent uses a composite adjuvant system comprising squalene, tocopherol, and polysorbate 80 formulated as an oil-in-water emulsion. This composite adjuvant enhances the stability and immunogenicity of the S protein vaccine antigen, working synergistically to maintain prefusion conformation and amplify immune response.
2Reliability
If existing vaccines are used, then some protection is provided, but adequate protection against severe illness and mortality is not achieved, especially in individuals with comorbidities
Solution Approach 1:
The patent modifies the adjuvant composition by incorporating tocopherol (vitamin E) at specific concentrations (e.g., 1.3-22 mg per dose) to enhance the immunogenicity and protective efficacy of the vaccine. This parameter optimization aims to achieve robust protection against severe illness and mortality, particularly in vulnerable populations with comorbidities.
3Adaptability or versatility
If variants of SARS-COV-2 continue to emerge, then new strains appear, but existing vaccines do not provide adequate protection against circulating variants
Solution Approach 1:
The patent employs a universal vaccine design using the conserved prefusion S protein trimer as the antigen, which is highly conserved across SARS-COV-2 variants. The stabilized prefusion conformation presents conserved epitopes that can elicit broadly neutralizing antibodies, providing cross-protection against multiple circulating variants including D614G, B.1.1.7, B.1.351, and B.1.617.
Data Source
AI summary
Provided are novel vaccines for prophylactic treatment of SARS-COV-2 infections and COVID-19 and methods of making the vaccines, wherein the vaccines contain an oil-in-water emulsion comprising tocopherol and squalene.