Codon-Pair Deoptimized Live Attenuated SARS-CoV-2 Vaccine
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Solution Overview
Problem
Existing COVID-19 vaccines face challenges in addressing rapidly evolving SARS-CoV-2 variants that exhibit increased infectivity, morbidity, and the ability to evade infection- or vaccine-induced immunity, posing a significant threat to public health.
Innovation Solution
Development of a codon-pair deoptimized polynucleotide encoding SARS-CoV-2 proteins, such as the spike protein and non-structural proteins, to create a live attenuated SARS-CoV-2 vaccine candidate that reduces virus replication and translation efficiency while maintaining immune response efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If inactivated or subunit virus preparations are used for vaccination, then safety is improved, but immune response efficacy deteriorates
Solution Approach 1:
The patent extracts the essential immunogenic components (S protein, N protein, and non-structural proteins) from the complete virus, creating a recombinant vaccine that maintains safety while preserving immune response capability. The vaccine contains specific viral proteins that stimulate immunity without requiring the entire virus structure.
Solution Approach 2:
The vaccine employs a composite structure combining multiple viral proteins (S protein, N protein, and non-structural proteins) within a single vaccine formulation. This composite approach enhances immune response by targeting multiple viral antigens simultaneously, thereby improving efficacy while maintaining the safety profile of inactivated virus preparations.
2Object-affected harmful factors
If replication-defective virus vectors are used, then pathogenicity is reduced, but transmissibility and immune response deteriorate
Solution Approach 1:
The patent extracts the replication machinery requirements by using a recombinant virus system that expresses viral antigens without requiring full viral replication. This extraction of replication dependency reduces pathogenicity while maintaining the ability to stimulate immune response through antigen expression.
Solution Approach 2:
The vaccine utilizes parameter changes in viral protein expression levels and combinations (S protein, N protein, non-structural proteins) to optimize immune response. By adjusting the expression parameters of different viral antigens, the vaccine achieves enhanced immunogenicity without requiring full viral replication, thereby reducing pathogenicity.
3Reliability
If DNA/RNA molecules are used as vaccines, then safety is improved, but immunogenicity deteriorates
Solution Approach 1:
The patent uses a recombinant virus as an intermediary carrier to deliver viral antigens. This intermediary approach combines the safety of nucleic acid-based vaccines (recombinant DNA technology) with the high immunogenicity of viral vectors, as the recombinant virus structure naturally stimulates immune response while maintaining genetic safety through controlled antigen expression.
Data Source
AI summary
It is provided a polynucleotide encoding a) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein; and/or b) at least one non-structural SARS-CoV-2 protein selected from the group consisting of non-structural protein 7, non-structural protein 8, non-structural protein 9, non-structural protein 10, non-structural protein 11, non-structural protein 12, an endoribonuclease, and a 2′-O-methyltransferase, wherein the polynucleotide comprises or consists of at least one sequence part comprising codon-pair deoptimizations in comparison to the SARS-CoV-2 genome.