Codon-Optimized DNA Vaccine for Equine Encephalitis

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Solution Overview

Problem

Current vaccines for equine encephalitis viruses such as Venezuelan, eastern, and western equine encephalitis viruses are limited in their effectiveness and safety, with live-attenuated and formalin-inactivated vaccines causing adverse reactions and providing inadequate protection against aerosol challenges.

Innovation Solution

Development of a nucleotide sequence encoding structural proteins of equine encephalitis viruses, specifically codon-optimized for mammalian expression, used in eukaryotic expression vectors like pWRG7077, which are administered via particle-mediated epidermal delivery to elicit a robust immune response.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If live-attenuated vaccines are used, then long-lasting immunity is provided, but adverse reactions occur in approximately 25% of recipients

Engineering Contradiction:

Improveimmunity durationVSAvoidadverse reactions

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts only the essential immunogenic components (structural proteins E1, E2, E3, and 6K) from the complete virus, excluding the capsid protein and other viral elements. This is achieved through DNA vaccination where plasmids encode only these specific structural proteins, providing immunity without using the live attenuated virus that causes adverse reactions.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent introduces DNA plasmids as an intermediary carrier that encodes viral structural proteins. Instead of directly administering live attenuated virus, the DNA vaccine serves as an intermediary that instructs host cells to produce viral antigens, thereby eliciting immune response without exposing recipients to live virus and its associated adverse effects.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Object-affected harmful factors

If formalin-inactivated vaccines are used, then safety is improved, but frequent boosting is required to maintain detectable neutralizing antibody responses

Engineering Contradiction:

ImprovesafetyVSAvoidvaccination frequency

Core Design Contradiction:

Object-affected harmful factorsVSLoss of time

Solution Approach 1:

The patent extracts and utilizes only the essential structural proteins (E1, E2, E3, and 6K) through DNA encoding, eliminating the need for formalin inactivation processes. This DNA-based approach provides both safety (no live virus) and sustained immunity (reduced boosting frequency) by directing host cells to continuously produce viral antigens from the incorporated DNA plasmids.

Inventive Principle:

Principle #2Taking out (Extraction)

3Reliability

If existing vaccines are used, then protection against natural infection is provided, but protection against aerosol challenges is inadequate

Engineering Contradiction:

Improveprotection efficacyVSAvoidprotection scope

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent creates a universal DNA vaccine platform that can protect against multiple alphavirus encephalitides (VEEV, EEEV, WEEV) by encoding conserved structural proteins. The vaccine design targets essential viral components (E1, E2, E3 envelope proteins and 6K membrane protein) that are critical for viral assembly and pathogenesis across different virus types, providing broad-spectrum protection including aerosol challenge protection.

Inventive Principle:

Principle #6Universality (Multi-functionality)

4Object-affected harmful factors

If DNA vaccines are used, then safety is improved and production is simplified, but neutralizing antibody responses are initially low

Engineering Contradiction:

ImprovesafetyVSAvoidantibody response level

Core Design Contradiction:

Object-affected harmful factorsVSMeasurement precision

Solution Approach 1:

The patent optimizes several parameters to enhance DNA vaccine immunogenicity: (1) Codon optimization of viral structural protein sequences for mammalian expression, (2) Inclusion of specific structural proteins (E1, E2, E3, 6K) that elicit strong neutralizing antibodies, (3) Use of particle-mediated epidermal delivery for improved antigen presentation, and (4) Combination with adjuvants to amplify the immune response, thereby achieving high neutralizing antibody titers while maintaining safety.

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS9555090B2Equine encephalitis virus vaccines and methods of using thereof

Publication Date: 2017.01.31 THE UNITED STATES OF AMERICA AS REPESENTED BY THE SEC OF ARMY ON BEHALF OF THE U S ARMY MEDICAL RES INST OF INFECTIONS DISEASES

AI summary

Disclosed herein are nucleotide sequences which encode a plurality of structural proteins, except the capsid, of an equine encephalitis virus, wherein the nucleotide sequence is codon-optimized for mammalian expression. The nucleotide sequences are codon-optimized for expression in humans. As disclosed herein, the nucleotide sequences confer protection against Venezuelan equine encephalitis virus (VEEV), western equine encephalitis virus (WEEV), and/or eastern equine encephalitis virus (EEEV).