Recombinant Swinepox Virus IL18bp Cloning

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Solution Overview

Problem

There is a need for new viral vector products that can efficiently and stably express recombinant peptides or proteins in vivo, particularly for veterinary vaccines, as existing poxvirus recombinants have limitations in gene insertion regions and immunogenicity.

Innovation Solution

Recombinant swinepox viruses with foreign gene sequences inserted into the IL-18 binding protein (IL18bp) gene, allowing for efficient and stable expression and improved immunogenicity, particularly suited for producing vaccines against PCV2 infection in swine.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If foreign gene sequences are inserted into the TK region of swinepox virus, then recombinant viruses can be produced, but the expression stability and immunogenicity are limited

Engineering Contradiction:

Improveexpression stabilityVSAvoidcloning limitation

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent identifies and utilizes a specific gene region (IL-18bp gene, nucleotides 7745-8146) as a separate cloning site distinct from the traditional TK region. This segmentation allows independent manipulation and insertion of foreign genes into a specific genomic location that provides better expression stability while maintaining virus replication capability.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The invention demonstrates that different genomic regions of the swinepox virus have different qualities for gene expression. The IL-18bp gene region was found to provide superior local quality for foreign gene expression compared to the TK region, with enhanced stability and immunogenicity properties.

Inventive Principle:

Principle #3Local quality

2Productivity

If recombinant poxviruses are used for gene delivery, then expression levels can be elevated, but safety concerns arise from growth in mammalian cells

Engineering Contradiction:

Improveexpression levelVSAvoidsafety risk

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent converts the potential harm of virus growth in mammalian cells into a benefit by deliberately selecting a cloning site (IL-18bp gene) that, when modified with foreign genes, results in reduced or abolished growth capability in mammalian cells like Vero cells. This ensures safety while maintaining the productivity advantage of poxvirus-based expression systems.

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

3Adaptability or versatility

If multiple foreign genes are inserted into the same viral vector, then vaccine coverage can be expanded, but the complexity of virus construction increases

Engineering Contradiction:

Improvevaccine coverageVSAvoidvirus construction complexity

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The IL-18bp gene region serves as a universal cloning site that can accommodate multiple different foreign gene sequences. The patent demonstrates versatility by successfully inserting different genes (ORF2, ORF3 of PCV2, and other foreign sequences) into the same genomic location, enabling multi-functional vaccine development without proportionally increasing construction complexity.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentEP3234159B1Recombinant swinepox virus and vaccines

Publication Date: 2019.06.12 CEVA SANTE ANIMALE SA

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AI summary

The present invention relates to novel recombinant swinepox viruses and their use in vaccine compositions. The recombinant swinepox viruses of the invention are produced 5 by inserting one or more foreign genes into IL-18 binding protein (IL18bp) gene of swinepox virus. The invention is particularly suited to produce swine vaccines, particularly for vaccinating swine against PCV2 infection.