Codon-Optimized SARS-CoV-2 DNA Vaccine Signal Peptide
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Solution Overview
Problem
Current vaccines against SARS-CoV-2, such as protein-based subunit vaccines, often induce undesired Th2-skewed immune responses, and DNA vaccines may be less effective in inducing neutralizing antibodies, necessitating the development of a safe and effective vaccine that can be rapidly produced and deployed globally.
Innovation Solution
A DNA vaccine comprising a codon-optimized SARS-CoV-2 spike glycoprotein with a human IgG2 heavy chain signal peptide, encoded by specific nucleotide sequences, is administered to induce an immune response, offering a Th1-biased immune response and neutralizing antibody production.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If protein-based subunit vaccines are used, then the vaccine can be produced safely, but it induces undesired Th2-skewed immune responses
Solution Approach 1:
The patent changes the molecular parameters of the vaccine by using codon-optimized DNA sequences that direct the production of the spike protein with specific post-translational modifications, thereby altering the immune response profile from Th2-skewed to Th1-biased while maintaining safety
2Productivity
If DNA vaccines are used to improve immune response, then neutralizing antibody production is enhanced, but effectiveness in inducing neutralizing antibodies is reduced
Solution Approach 1:
The patent optimizes codon usage parameters and signal peptide sequences to enhance protein expression levels and quality, thereby improving the effectiveness of DNA vaccines in inducing neutralizing antibodies while maintaining high productivity
Solution Approach 2:
The patent uses a human IgG2 heavy chain signal peptide as an intermediary element to facilitate proper protein folding, secretion, and immune recognition, thereby bridging the gap between DNA vaccine administration and effective neutralizing antibody induction
3Productivity
If vaccine production is accelerated for rapid deployment, then global deployment speed is improved, but manufacturing complexity increases
Solution Approach 1:
The patent uses synthetic DNA sequences that can be rapidly copied and synthesized using automated DNA synthesis technology, enabling fast vaccine production without complex manufacturing processes
Solution Approach 2:
The patent employs universal plasmid vectors and codon optimization strategies that can be applied across different manufacturing platforms, simplifying the manufacturing process while enabling rapid scale-up for global deployment
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 vaccine elicits significant and long-lasting Th1-skewed immune responses and neutralizing antibodies, providing protection against SARS-CoV-2, with improved immunogenicity through needle-free administration, even at lower doses, and stability across various climates.
Implementation Method 1
The nucleotide sequence is codon-optimized for mammalian expression
Implementation Method 2
A DNA vaccine comprising a codon-optimized SARS-CoV-2 spike glycoprotein... encoded by specific nucleotide sequences
Data Source
AI summary
A synthetic DNA vaccine against SARS-CoV-2 infection comprises a codon-optimized coding sequence for optimal mammalian expression of a pSARS2 spike glycoprotein (pSARS2-S). The signal peptide may be replaced with the signal peptide from the human IgG2 heavy chain. Systemic S1-specific IgG antibodies and neutralizing antibodies (nAbs) were significantly induced in mice at 2 weeks-post three injections with 100 μg of the pSARS2-S vaccine via intramuscular (IM) needle injection. IM immunization induced Th1-skewed and long-lasting IgG response in BALB/c mice. Immunogenicity and induction of nAbs were enhanced with a needle-free delivery system, wherein two doses were sufficient to elicit significant levels of systemic S1-specific IgG antibodies and nAbs via IM or intradermal immunization.