Recombinant RVF Viruses with NSs and NSm Deletions for DIVA
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Solution Overview
Problem
Current vaccines for Rift Valley fever (RVF) virus lack efficacy, safety, and the ability to differentiate between naturally infected and vaccinated animals, posing challenges in public and veterinary health, especially in resource-poor settings and during outbreaks.
Innovation Solution
Development of highly attenuated recombinant RVF viruses with precise molecular markers, containing deletions in major virulence factors NSs and NSm, and incorporating a reporter gene like eGFP, using a reverse genetics system for production, allowing for differentiation of naturally infected and vaccinated animals through serology.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current vaccines are used for RVF virus prevention, then vaccination coverage can be achieved, but they lack efficacy and safety, and cannot differentiate between naturally infected and vaccinated animals
Solution Approach 1:
The patent extracts and removes the virulence genes (NSs and NSm) from the RVF virus genome to create an attenuated vaccine strain. This extraction of harmful genetic elements reduces viral virulence while preserving immunogenicity, thereby improving vaccine safety and efficacy without compromising the ability to differentiate vaccinated from naturally infected animals through serological testing
Solution Approach 2:
The patent incorporates a reporter gene (eGFP) into the vaccine virus genome, which expresses a fluorescent protein marker. This molecular 'color change' or visible marker enables serological differentiation between vaccinated animals (who have antibodies against eGFP) and naturally infected animals (who do not), solving the differentiation capability problem
2Reliability
If multiple booster inoculations are administered to ensure protection, then immunity can be maintained, but the number of administrations increases and resource requirements increase
Solution Approach 1:
The patent employs a reverse genetics system that allows precise engineering of the virus genome before vaccination. By pre-attenuating the virus through genetic modification (removal of virulence genes) and incorporating reporter genes, the vaccine provides robust long-lasting immunity after a single administration, eliminating the need for multiple booster shots and thereby improving vaccination efficiency
3Object-affected harmful factors
If deletions are made in virulence genes to attenuate the virus, then safety is improved, but vaccine development complexity increases
Solution Approach 1:
The patent uses a reverse genetics system as an intermediary tool to facilitate precise genetic modifications. This system allows researchers to make controlled deletions in virulence genes (NSs and NSm) and insert reporter genes through a standardized molecular biology platform, thereby reducing the actual complexity of virus engineering while achieving the desired attenuation and differentiation capabilities
Data Source
AI summary
Described herein are recombinant RVF viruses comprising deletions in one or more viral virulence genes, such as NSs and NSm. The recombinant RVF viruses, generated using a plasmid-based reverse genetics system, can be used as vaccines to prevent infection of RVF virus in livestock and humans. As described herein, the recombinant RVF viruses grow to high titers, provide protective immunity following a single injection and allow for the differentiation between vaccinated animals and animals infected with wild-type RVF virus.