ASFV MGF Gene Deletion Vaccine for Swine Protection
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Solution Overview
Problem
There is no effective vaccine available for African Swine Fever (ASF) caused by the highly virulent ASFV Georgia 2007 isolate, and existing vaccination methods have failed to induce protective immunity against the disease.
Innovation Solution
A recombinant mutant ASFV-G ΔMGF virus is developed by deleting a large portion of the Multi Gene Family (MGF) genes from the ASFV-G genome, creating a live attenuated vaccine that can protect animals from clinical ASF disease and differentiate between vaccinated and infected animals using a genetic DIVA strategy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional vaccination methods (infected cell extracts, inactivated virions, etc.) are used, then vaccination is attempted, but protective immunity is not induced
Solution Approach 1:
The patent extracts and removes specific MGF genes (MGF 110, MGF 300, MGF 360, MGF 505) from the ASFV genome to create an attenuated vaccine strain. This extraction of virulence-associated genes reduces pathogenicity while maintaining immunogenicity, solving the problem of inducing protective immunity without causing severe disease.
Solution Approach 2:
The patent changes the genetic parameters of the ASFV by deleting specific MGF gene sequences, transforming the virus from a highly virulent state to an attenuated state suitable for vaccination. This parameter change in the viral genome enables the virus to provide protective immunity while reducing harmful effects.
2Reliability
If the virus is attenuated by gene deletion, then protective immunity is induced, but the ability to distinguish vaccinated from infected animals is compromised
Solution Approach 1:
The patent applies local quality by making a specific modification to the MGF 505 gene (changing a T to C at a specific position) in addition to the deletions. This localized genetic marker maintains the attenuated phenotype for immunity while creating a distinguishable genetic signature that allows DIVA strategy implementation.
Solution Approach 2:
The patent introduces a genetic marker as an intermediary element within the MGF 505 gene that serves dual purposes: maintaining vaccine attenuation and enabling differentiation between vaccinated and infected animals through diagnostic testing.
3Object-affected harmful factors
If MGF genes are deleted to attenuate the virus, then virulence is reduced, but vaccine effectiveness against heterologous strains may be limited
Solution Approach 1:
The patent deletes specific MGF genes that are most strongly associated with virulence (MGF 110, MGF 300, MGF 360, MGF 505) while leaving other genomic regions intact. This partial deletion strategy achieves sufficient attenuation for safety while preserving enough viral antigens to provide broad cross-protection against heterologous ASFV strains.
Data Source
AI summary
African swine fever virus (ASFV) is the etiological agent of a contagious and often lethal viral disease of domestic pigs. Control of ASF has been hampered by the unavailability of vaccines. Experimental vaccines have been derived from naturally occurring, cell culture-adapted, or genetically modified live attenuated ASFVs; however, these vaccines are only successful when protecting against homologous viruses. Among viral genes reported to be involved in virulence are components of the multi gene family (MGF). Here we report the construction of a recombinant ΔMGF virus derived from the highly virulent ASFV Georgia 2007 (ASFV-G) isolate. In vivo, ASFV-G ΔMGF administered intramuscularly (IM) to swine at either 102 or 104 HAD50 are completely attenuated; the inoculated animals are completely asymptomatic. Animals infected with 102 or 104 HAD50 of ASFV-G ΔMGF are protected against the presentation of clinical disease when challenged at 28 days post infection with the virulent parental strain Georgia 2007.