Reverse Genetics Schmallenberg Virus Vaccine Plasmid System

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Solution Overview

Problem

Current Schmallenberg virus (SBV) vaccine compositions lack complete genome sequences and are not fully attenuated, posing safety concerns and inefficiencies in inducing strong humoral immune responses.

Innovation Solution

Development of a reverse genetics system using plasmids encoding SBV S, M, and L segments for producing recombinant SBV vaccines, ensuring high safety and efficacy by engineering viruses with reduced virulence and inducing robust immune responses.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If wildtype SBV is used for vaccine production, then strong immune response is achieved, but safety is compromised due to virulence

Engineering Contradiction:
ImprovesafetyVSAvoidvirulence
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The SBV genome is divided into three separate segments (S, M, and L) that are cloned into individual plasmids. This segmentation allows for controlled propagation and engineering of the virus, enabling the creation of attenuated strains through systematic manipulation of each segment while maintaining safety.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent employs reverse genetics to modify viral parameters by introducing mutations in the plasmid-encoded genome segments. These parameter changes result in attenuated virus strains with reduced virulence while preserving immunogenicity, thereby improving safety without sacrificing vaccine efficacy.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If reverse genetics system is used to engineer attenuated virus, then safety is improved, but manufacturing complexity increases

Engineering Contradiction:
ImprovesafetyVSAvoidmanufacturing complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The reverse genetics system divides the viral genome into discrete plasmid segments, each encoding a specific genome segment. This segmentation simplifies the manufacturing process by allowing independent cloning, propagation, and quality control of each segment before assembly, thereby reducing overall manufacturing complexity despite the sophisticated approach.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The reverse genetics system developed in this patent creates a universal platform that can be used to produce multiple attenuated SBV strains and potentially other bunyaviruses. The standardized plasmid constructs and transfection protocols establish a multi-functional system that reduces complexity by providing a reusable framework for vaccine production.

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

3Manufacturing precision

If complete genome sequence is obtained, then vaccine efficacy is improved, but sequencing and assembly difficulty increases

Engineering Contradiction:
Improvevaccine efficacyVSAvoidsequencing difficulty
Core Design Contradiction:
Manufacturing precisionVSDifficulty of detecting and measuring

Solution Approach 1:

The complete SBV genome was obtained by sequencing and assembling the three separate plasmid-encoded segments (S, M, and L). This segmentation approach simplified the sequencing process by breaking down the complex viral genome into manageable pieces that could be individually sequenced and then accurately reassembled, thereby improving manufacturing precision without overwhelming sequencing difficulty.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent creates accurate copies of the complete SBV genome through plasmid-based cloning. These copied sequences serve as reference standards for vaccine production and quality control, enabling precise manufacturing while avoiding the need to repeatedly perform difficult sequencing operations. The cloned plasmids act as stable, reproducible templates.

Inventive Principle:
Principle #26Copying

Data Source

PatentUS9556419B2Reverse genetics Schmallenberg virus vaccine compositions, and methods of use thereof
Publication Date: 2017.01.31 MERIAL LTD
  • US9556419B2 patent drawing
  • US9556419B2 patent drawing
  • US9556419B2 patent drawing

AI summary

The present invention relates to compositions comprising replication defective Schmallenberg virus vaccines, methods of producing the vaccines, and the administration of such vaccines to animals, including ovines and bovines. The invention further relates to methods for providing long-term protective immunity against Schmallenberg in animals, including ovines and bovines.