Herpes Antigen Nucleic Acid Codon Optimization

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Solution Overview

Problem

Current vaccine strategies for herpesviruses, including DNA vaccines, face challenges in immunogenicity, especially when scaled up to larger animals, and there is a need for effective and economical vaccines that induce robust immune responses against herpesviruses such as HSV and CMV.

Innovation Solution

Development of nucleic acid molecules encoding herpes virus antigens, including proteins and fragments thereof, with optimized codon usage and delivery methods like electroporation, combined with consensus sequences and antigenic tags, to enhance immunogenicity and stability, and the creation of multivalent vaccines that co-express multiple antigens for broader immunity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If DNA vaccines are used for herpesviruses, then vaccination can be achieved, but immunogenicity is insufficient especially in larger animals

Engineering Contradiction:
Improvevaccine efficacyVSAvoidimmunogenicity across different animal sizes
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies parameter changes by optimizing codon usage in the nucleic acid sequences to match host cell preferences, thereby enhancing protein expression levels and immunogenicity. This resolves the contradiction by modifying the genetic parameters of the vaccine to achieve reliable protection across different animal sizes without requiring different vaccine formulations.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses composite approaches by combining multiple antigens (gB, gH, gL, gC, gD) into single nucleic acid molecules or vaccine formulations. This composite strategy enhances overall immunogenicity by targeting multiple viral proteins simultaneously, thereby improving vaccine efficacy and adaptability across different host species and sizes.

Inventive Principle:
Principle #40Composite materials

2Adaptability or versatility

If multiple antigens are included in vaccine to broaden immunity, then vaccine complexity increases, but manufacturing and delivery become more difficult

Engineering Contradiction:
Improvebreadth of immunityVSAvoidvaccine structure
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent merges multiple antigen-encoding sequences into single nucleic acid molecules or co-delivers them as part of a unified vaccine composition. This combining approach achieves broad immunity against multiple herpesvirus antigens while simplifying manufacturing and delivery compared to administering separate vaccines for each antigen.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent creates universal vaccine constructs that can encode and express multiple different herpesvirus antigens (gB, gH, gL, gC, gD) within a single formulation. This multi-functional design provides broad protective immunity against diverse herpesvirus strains and types without requiring separate vaccine formulations for each antigen.

Inventive Principle:
Principle #6Universality (Multi-functionality)

3Productivity

If codon optimization is applied to enhance expression, then immunogenicity improves, but sequence homology to natural virus decreases

Engineering Contradiction:
Improveprotein expression levelVSAvoidsequence homology
Core Design Contradiction:
ProductivityVSStability of the object's composition

Solution Approach 1:

The patent applies codon optimization by changing the nucleotide sequence while maintaining the same amino acid sequence. This parameter change in the genetic code enhances protein expression levels and immunogenicity without altering the actual protein structure or its homology to natural viral proteins, thereby resolving the contradiction between productivity and sequence composition stability.

Inventive Principle:
Principle #35Parameter changes

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 approach results in improved immunogenicity and immune response induction, providing effective protection against herpesviruses with enhanced stability and expression, addressing the limitations of existing vaccines by increasing the breadth of immunity and vaccine efficacy.

Implementation Method 1

delivery methods like electroporation

Methodology Applied
Scientific EffectElectroporation:

Data Source

PatentUS9994619B2Nucleic acid molecules encoding novel herpes antigens, vaccine comprising the same, and methods of use thereof
Publication Date: 2018.06.12 THE TRUSTEES OF THE UNIV OF PENNSYLVANIA
  • US9994619B2 patent drawing
  • US9994619B2 patent drawing
  • US9994619B2 patent drawing

AI summary

Provided herein are nucleic acid sequences that encode novel consensus amino acid sequences of herpes virus antigens, as well as genetic constructs/vectors and vaccines expressing the sequences. Also provide herein are methods for generating an immune response against herpes virus using the vaccines that are provided.