Chimeric Insect-Specific Flavivirus Vaccine Design

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Solution Overview

Problem

Current vaccines for flaviviruses, such as West Nile fever and dengue, face challenges including moderate immune responses, complex production processes, and risks of reversion to pathogenicity, while diagnostic tools using inactivated or attenuated viruses may lack specificity and safety.

Innovation Solution

Development of chimeric insect-specific flaviviruses and proteins combining amino acid sequences from insect-specific flaviviruses with immunogenic sequences from vertebrate-infecting flaviviruses, allowing for the creation of vaccines and diagnostics that elicit immune responses without replicating in vertebrate cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If inactivated vaccines are used, then production is simpler, but immune response is moderate or partial requiring multiple doses

Engineering Contradiction:

Improvevaccine production simplicityVSAvoidimmune response strength

Core Design Contradiction:

Ease of manufactureVSReliability

Solution Approach 1:

The patent creates chimeric viruses by combining components from different flaviviruses - insect-specific flavivirus structural proteins (C, prM, E) with vertebrate-infecting flavivirus immunogenic sequences (NS1, prM, E). This composite structure enables the vaccine to elicit strong immune responses while maintaining safety through insect-specific replication restriction.

Inventive Principle:

Principle #40Composite materials

2Reliability

If attenuated vaccines are used, then robust immune response is induced, but risk of reversion to pathogenicity exists

Engineering Contradiction:

Improveimmune response strengthVSAvoidreversion to pathogenicity risk

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The chimeric vaccine separates the immunogenic functions into distinct modules: insect-specific flavivirus provides the replication-restricted structural framework (C, prM, E proteins) while vertebrate-infecting flavivirus contributes immunogenic non-structural and envelope proteins (NS1, prM, E). This segmentation allows robust immune stimulation without the risk of reversion to pathogenicity.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The insect-specific flavivirus structural proteins act as an intermediary that restricts viral replication to insect cells, preventing the vaccine from causing disease in vertebrates while still allowing sufficient replication to induce robust immune responses. This intermediary mechanism eliminates the reversion risk associated with traditional attenuated vaccines.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Ease of manufacture

If inactivated viruses are used for diagnostics, then production is simpler, but specificity is reduced

Engineering Contradiction:

Improvediagnostic production simplicityVSAvoiddiagnostic specificity

Core Design Contradiction:

Ease of manufactureVSMeasurement precision

Solution Approach 1:

The chimeric diagnostic virus combines insect-specific flavivirus structural proteins with vertebrate-infecting flavivirus immunogenic sequences, enabling highly specific detection of vertebrate-infecting flavivirus antibodies while maintaining simple production in insect cell lines. The composite structure preserves epitope integrity for specific antibody binding.

Inventive Principle:

Principle #40Composite materials

Data Source

PatentUS11572390B2Chimeric insect-specific flaviviruses

Publication Date: 2023.02.07 THE UNIVERSITY OF QUEENSLAND

AI summary

Chimeric proteins that comprise one or more amino acid sequences of an insect-specific flavivirus and one or more other immunogenic proteins are provided. The chimeric proteins are suitably capable of forming virus particles. The chimeric protein and/or virus particle may be suitable for delivery to a subject to elicit an immune response to a pathogen and/or for diagnosis or detection of a pathogen. Also provided are nucleic acids and vectors encoding the chimeric proteins, and isolated chimeric insect-specific flaviviruses comprising the chimeric proteins and/or nucleic acids.