HCV DNA Vaccine Codon Optimization for Immunogenicity

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Solution Overview

Problem

Current vaccine development for Hepatitis C (HCV) faces challenges due to the virus's persistent nature, lack of effective treatments, and the need for novel immune therapy strategies, as existing vaccines do not provide antibody-mediated protection and DNA vaccines face decreased immunogenicity in larger animals.

Innovation Solution

Development of nucleic acid molecules encoding proteins such as HCV NS4B, NS5A, and NS5B with optimized codon usage and immunoglobulin leader sequences, combined with electroporation for enhanced delivery, to induce strong cellular immune responses.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If DNA vaccines are used for HCV, then prophylactic and therapeutic immunity can be induced, but immunogenicity decreases in larger animals

Engineering Contradiction:

Improveprophylactic and therapeutic immunityVSAvoidimmunogenicity

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent optimizes codon usage in the DNA vaccine construct to match host cell preferences, thereby improving protein expression efficiency and immunogenicity in larger animals while maintaining the ability to induce protective immunity

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent uses consensus sequences derived from multiple HCV strains to create a representative antigen that mimics the diverse viral population, enhancing broad immune recognition without requiring strain-specific optimization for each animal model

Inventive Principle:

Principle #26Copying

2Reliability

If existing vaccines are developed for HCV, then antibody-mediated protection is expected, but HCV infection does not appear to be antibody mediated

Engineering Contradiction:

Improveprotective immunityVSAvoidantibody-mediated protection mechanism

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

Instead of designing vaccines based on antibody-mediated protection (the conventional approach), the patent inverts the strategy by focusing on inducing cell-mediated immune responses, specifically CD4+ and CD8+ T cell responses, which are the actual protective mechanisms against HCV

Inventive Principle:

Principle #13The other way round (Inversion)

3Reliability

If standard treatment protocols are used for chronic HCV, then some individuals respond to treatment, but treatment is extremely difficult and expensive

Engineering Contradiction:

Improvetreatment responseVSAvoidtreatment cost

Core Design Contradiction:

ReliabilityVSLoss of energy

Solution Approach 1:

The patent employs DNA vaccination as a preliminary prophylactic or early therapeutic intervention to induce immune responses before chronic infection is established or in early infection stages, potentially preventing the need for expensive long-term antiviral treatments

Inventive Principle:

Principle #10Preliminary action

Data Source

PatentUS9156891B2Vaccines and methods for using the same

Publication Date: 2015.10.13 INOVIO PHARMACEUTICALS INC

AI summary

Improved anti-HCV immunogens and nucleic acid molecules that encode them are disclosed. Immunogens disclosed include those having consensus HCV genotype 1a, including for example, NS4B, NS5A and NS5B. Pharmaceutical composition, recombinant vaccines comprising and live attenuated vaccines are disclosed as well methods of inducing an immune response in an individual against HCV are disclosed.