Codon Deoptimized Arenavirus Vaccine for Safe Immunization

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Solution Overview

Problem

Current vaccines and therapies for arenavirus infections, such as Lassa fever, lack effectiveness and safety due to limited options and the need for early intravenous administration of ribavirin, which has significant side effects, and there is a lack of understanding in generating attenuated arenaviruses for vaccine development due to the inability to genetically manipulate the arenavirus genome.

Innovation Solution

Development of a codon deoptimized live-attenuated arenavirus vaccine comprising nucleoprotein (NP), glycoprotein precursor (GPC), or matrix (Z) protein, which reduces protein expression and viral attenuation, providing a safe and effective immunological composition for preventing and treating arenavirus infections.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If ribavirin is administered for treating arenavirus infections, then antiviral efficacy is achieved, but significant side effects and need for early intravenous administration occur

Engineering Contradiction:

Improveantiviral efficacyVSAvoidside effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses a live-attenuated vaccine that provides temporary controlled viral replication to stimulate immunity, replacing the need for long-term ribavirin treatment with a single or limited-dose vaccination approach

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The vaccine is administered before infection occurs, pre-stimulating the immune system with attenuated virus to prevent the need for emergency ribavirin treatment after infection

Inventive Principle:

Principle #10Preliminary action

2Reliability

If live-attenuated arenavirus vaccine is developed, then protective immune response is induced, but reversion to parental virulent form may occur

Engineering Contradiction:

Improveprotective immune responseVSAvoidviral attenuation stability

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent employs multiple genetic modifications including codon deoptimization, amino acid substitutions, and deletions in the L segment that collectively stabilize the attenuated phenotype while maintaining immunogenicity

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The vaccine virus is constructed as a composite with multiple attenuating mutations distributed across different genomic segments, creating a stable attenuated strain that combines multiple safety mechanisms

Inventive Principle:

Principle #40Composite materials

3Reliability

If codon deoptimized polynucleotide is used in vaccine, then viral attenuation is reduced and safety is improved, but protein expression is decreased

Engineering Contradiction:

Improvevaccine safetyVSAvoidviral protein expression

Core Design Contradiction:

ReliabilityVSQuantity of substance

Solution Approach 1:

The patent uses codon deoptimization to alter translation efficiency and reduce protein expression levels, thereby attenuating the virus while maintaining immunogenicity through controlled expression

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

Codon deoptimization is applied selectively to specific genes or regions of the arenavirus genome rather than uniformly across all genes, allowing differential expression levels that balance safety and immunogenicity

Inventive Principle:

Principle #3Local quality

Data Source

PatentUS10342861B2Arenavirus vaccine

Publication Date: 2019.07.09 THE SCRIPPS RES INST

AI summary

The invention relates to compositions and methods for preventing or treating arenavirus related diseases and disorders through the administration to a subject in need thereof a live-attenuated virus (LAV), wherein the LAV is a codon deoptimized (CD) arenavirus.