Glycoengineered SARS-CoV-2 Spike Vaccine for Conserved Epitope Exposure
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Solution Overview
Problem
Existing COVID-19 vaccines face challenges in effectively addressing emerging genetic variants of SARS-COV-2 due to the shielding of highly conserved epitopes by glycans, leading to suboptimal immune responses.
Innovation Solution
Glycoengineering the SARS-COV-2 spike protein to remove N-glycan shields and expose conserved epitopes through N-glycan trimming, preserving the protein's tertiary structure, thereby enhancing immune response.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If the spike protein is extensively glycosylated to maintain its native structure, then the tertiary structure is preserved, but the highly conserved epitopes are shielded by glycans leading to suboptimal immune response
Solution Approach 1:
The patent removes N-glycan shields from the spike protein through enzymatic deglycosylation while preserving the protein's tertiary structure. This extraction of the harmful glycan component exposes the highly conserved epitopes that were previously shielded, enabling the immune system to recognize and respond to these critical regions more effectively.
Solution Approach 2:
The patent applies different glycosylation states to different regions of the spike protein. Specifically, N-glycans are removed from regions containing highly conserved epitopes to expose them to the immune system, while O-glycans are retained in other regions to maintain local structural stability and protein folding. This localized modification strategy optimizes both immune recognition and structural integrity.
2Reliability
If N-glycans are removed to expose conserved epitopes, then immune response is enhanced, but the native structure of the spike protein is altered
Solution Approach 1:
The patent selectively removes only N-glycans while preserving O-glycans and the underlying protein structure. This localized approach allows exposure of epitopes in N-glycan-rich regions without compromising the overall tertiary structure stability that depends on O-glycosylation and disulfide bonds in other regions of the spike protein.
Solution Approach 2:
The patent modifies the glycosylation parameter of the spike protein by changing the presence/absence state of N-glycans while maintaining other structural parameters. This parameter change exposes conserved epitopes for immune recognition while preserving the protein's folding, stability, and antigenic determinants through controlled enzymatic treatment conditions.
3Adaptability or versatility
If glycoengineering is applied to trim N-glycans, then conserved epitopes are exposed for broader variant protection, but the manufacturing process becomes more complex
Solution Approach 1:
The patent uses enzymatic deglycosylation as an intermediary process to achieve the desired glycoengineered spike protein. Enzymes such as PNGase F or Endo H serve as mediators that selectively remove N-glycans under controlled conditions, providing a scalable and reproducible manufacturing approach that balances process complexity with the benefit of broad variant protection.
Data Source
AI summary
The present disclosure provides a glycoengineered SARS-COV-2 spike protein which is capable of eliciting an enhanced immune response relative to a native spike protein of SARS-COV-2 and its variants. The glycoengineered spike protein exposes the glycosylation sites and at the same time preserves the tertiary structure of the spike protein. The present disclosure therefore provides improved immunogens, vaccines, and methods for better prevention and treatment of the emerging coronavirus infections.