Rationally developed african swine fever attenuated virus strain protects against challenge with parental virus georgia 2007 isolate
Inventors
Borca, Manuel V. • Gladue, Douglas P. • Holinka-Patterson, Lauren G. • Risatti, Guillermo R. • O'Donnell, Vivian K.
Assignees
University of Connecticut • US Department of Agriculture USDA
Publication Number
US-9808520-B1
Publication Date
2017-11-07
Expiration Date
2036-07-01
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Abstract
African swine fever virus (ASFV) is the etiological agent of a contagious, often lethal viral disease of domestic pigs. The control of African Swine Fever (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. We have constructed a recombinant Δ9GL/ΔUK virus derived from the highly virulent ASFV Georgia 2007 (ASFV-G) isolate by deleting the specific virulence-associated 9GL (B119L) and the UK (DP96R) genes. In vivo, ASFV-G Δ9GL/ΔUK administered intramuscularly to swine even at relatively high doses (106 HAD50) does not induce disease. Importantly, animals infected with 104 or 106 HAD50 are solidly protected against the presentation of clinical disease when challenged at 28 days post infection with the virulent parental strain Georgia 2007.
Core Innovation
African swine fever virus (ASFV) is a highly contagious and often lethal viral disease affecting domestic pigs. The control of ASF has been challenging due to the absence of effective vaccines. Previous experimental vaccines derived from naturally occurring, cell culture-adapted, or genetically modified live attenuated ASFVs have only been successful against homologous viruses.
The invention relates to the construction of a recombinant African Swine Fever Virus (ASFV) live attenuated candidate strain vaccine for the highly virulent Georgia 2007 isolate ASFV-G. This vaccine is a novel recombinant mutant designated ASFV-G Δ9GL/ΔUK, produced by deleting large portions of two virulence-associated genes, 9GL (B119L) and UK (DP96R), from the parental ASFV-G. The modified virus, when administered intramuscularly to swine even at high doses, does not cause disease but induces solid protection against challenge with the parental virulent virus.
Claims Coverage
The patent discloses five claims with two independent claims covering the recombinant mutant ASFV-G Δ9GL/ΔUK virus and methods related to vaccination and protection of swine.
Recombinant ASFV-G Δ9GL/ΔUK mutant virus with specific gene deletions
The mutant ASFV-G Δ9GL/ΔUK virus comprises two deletions at the nucleotide level: a 173-nucleotide deletion in the 9GL gene resulting in a mutant 9GL protein lacking amino acids #11 to #68 (58 amino acids deleted), and a 255-nucleotide deletion in the UK gene resulting in a mutant UK protein lacking amino acids #1 to #85 (85 amino acids deleted).
Live attenuated vaccine composition comprising the recombinant mutant virus
A vaccine composition against ASFV-G comprising the recombinant mutant ASFV-G Δ9GL/ΔUK virus as the active immunizing agent.
Method for protecting swine against ASFV-G using live attenuated vaccine
Administration of an amount of live attenuated ASFV-G Δ9GL/ΔUK vaccine effective to protect swine from clinical African Swine Fever disease caused by ASFV-G.
Effective immunizing dosage range for protection
The vaccine is administered in a dosage ranging from 10^4 HAD50 to 10^6 HAD50 of the recombinant ASFV-G Δ9GL/ΔUK virus to confer protection.
The claims cover the novel genetically engineered ASFV-G Δ9GL/ΔUK mutant virus characterized by dual deletions in virulence genes, its use in vaccine compositions, and methods for protecting swine from ASF by administering effective doses of this live attenuated vaccine.
Stated Advantages
The recombinant virus is fully attenuated and does not induce disease symptoms in swine even at relatively high doses.
Vaccination with ASFV-G Δ9GL/ΔUK induces solid protection against clinical disease upon challenge with the highly virulent parental ASFV-G strain.
The vaccine offers a genetic marker (DIVA) capability, allowing differentiation between vaccinated animals and those infected with wild-type ASFV-G strains.
The inventive vaccine approach is based on rational design targeting conserved virulence-associated genes, improving predictability and effectiveness compared to singular gene deletions.
Documented Applications
Use as a livestock vaccine to immunize domestic swine against African Swine Fever caused by the highly virulent ASFV Georgia 2007 isolate.
Method for protecting swine against ASF by intramuscular, subcutaneous, or intranasal administration of the live attenuated ASFV-G Δ9GL/ΔUK vaccine.
Use as a genetic marker vaccine enabling differentiation between vaccinated animals and naturally infected animals through genetic DIVA strategies.
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