SARS-CoV-2 pDNA Vaccine Sequence Optimization for Thermostable Immunity
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Solution Overview
Problem
Current vaccines for SARS-CoV-2, such as mRNA-based and adenovirus vector vaccines, face challenges with stability, storage requirements, allergic reactions, and efficacy in individuals with pre-existing antibodies, while plasmid DNA (pDNA) vaccines offer advantages but require optimization for enhanced efficacy and stability.
Innovation Solution
Design and synthesis of pDNA vaccines targeting SARS-CoV-2 S protein determinants, optimized with codon adaptation, GC content, and CpG site modifications, administered without encapsulation, to induce robust humoral and cellular immune responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If mRNA-based vaccines are used to induce immune responses, then high immunogenicity is achieved, but storage stability deteriorates and complex delivery requirements increase
Solution Approach 1:
The patent uses plasmid DNA as a simplified copy or alternative form of the antigen-encoding information, replacing the complex mRNA structure with a more stable DNA plasmid that can be stored and transported without special conditions while still inducing the desired immune response
Solution Approach 2:
The patent changes the molecular parameter from RNA to DNA, fundamentally altering the stability characteristics while maintaining the immunogenic function. The plasmid DNA structure with its circular configuration and supercoiling provides inherent stability against degradation
2Reliability
If adenovirus vector vaccines are used to achieve high immunogenicity, then effective immune responses are induced, but allergic reactions and blood clot risks increase
Solution Approach 1:
The patent extracts only the essential antigen-encoding function from the adenovirus vector system, using a minimal plasmid DNA construct that lacks the viral components responsible for allergic reactions and blood clot risks while retaining the ability to induce immune responses
Solution Approach 2:
The plasmid DNA vaccine uses a simple, non-integrating, transient expression system that avoids the persistent viral components of adenovirus vectors, effectively using a disposable genetic construct that performs its function and then degrades without long-term presence in the host
3Stability of the object's composition
If pDNA vaccines are used to improve storage stability, then thermostability is achieved, but immune response magnitude may be insufficient
Solution Approach 1:
The patent applies preliminary optimization to the plasmid DNA sequence including codon adaptation to human cells, incorporation of CpG motifs to enhance immune recognition, and optimization of GC content to ensure efficient transcription and translation, thereby pre-configuring the plasmid for maximal immune response before administration
Solution Approach 2:
The patent optimizes multiple parameters of the plasmid DNA including sequence composition, CpG content, and codon usage to enhance immunogenicity while maintaining the inherent thermostability of the DNA structure
Data Source
AI summary
A pDNA-based vaccine against SARS-COV-2 and methods for preventing or treating COVID-19 using it.