Development of a novel live attenuated African Swine Fever vaccine based in the deletion of gene I177L
Inventors
Gladue, Douglas P. • Borca, Manuel V.
Assignees
US Department of Agriculture USDA
Publication Number
US-11007263-B2
Publication Date
2021-05-18
Expiration Date
2039-09-24
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Abstract
Provided herein are details on the construction of a recombinant African Swine Fever Virus (ASFV) live attenuated vaccine for prevention of ASF caused by various strains of ASFV, such as the highly virulent Georgia 2007 isolate (“ASFV-G”). An exemplary vaccine comprises the ASFV-GΔI1771 modified virus, a recombinant ASFV-G modified by deleting a portion of the I177L ORF rendering the I177L gene nonfunctional.
Core Innovation
The invention describes a genetically modified African Swine Fever Virus (ASFV) live attenuated vaccine designed to prevent African Swine Fever (ASF), including disease caused by highly virulent strains such as the Georgia 2007 isolate (ASFV-G). The vaccine comprises a modified virus termed ASFV-GΔI177L, produced by deleting a portion of the I177L open reading frame (ORF) which renders the I177L gene nonfunctional, resulting in an attenuated virus.
African Swine Fever is a contagious viral disease affecting swine with a high mortality rate, particularly from strains like ASFV-G. The disease is endemic in various global regions including sub-Saharan Africa, parts of Europe, and Asia, with outbreaks causing severe economic impacts. Current control measures rely on quarantine and slaughter due to the absence of a commercial vaccine. Previous vaccine attempts using infected cell extracts or inactivated virions have failed to induce protective immunity. Thus, there is a significant need for an effective vaccine to provide protection against lethal presentations of ASF.
Claims Coverage
The patent includes seven claims featuring two independent claims covering the genetically modified virus and a recombinant ASFV mutant virus with non-functional I177L gene.
Genetically modified virus genome comprising a viral genome at least 95% identical to SEQ ID NO: 2
The invention covers a genetically modified ASFV comprising a viral genome having at least 95% sequence identity to SEQ ID NO: 2, representing the ASFV-GΔI177L mutant virus with deletion in the I177L gene rendering it nonfunctional.
Vaccine composition comprising the genetically modified ASFV-Georgia 2007 isolate
The vaccine composition comprises the genetically modified virus defined above, specifically targeting African Swine Fever Virus of the ASFV-Georgia 2007 isolate (ASFV-G).
Method for protecting swine against ASFV-G by administering live attenuated vaccine
A method to protect swine against ASFV-G by administering an effective amount of the live attenuated vaccine comprising the genetically modified ASFV-GΔI177L virus, to prevent clinical ASFV-G disease.
Recombinant ASFV mutant virus with synthetic mutation in I177L or its regulatory elements
A recombinant mutant ASFV possessing a synthetic mutation in the I177L open reading frame or regulatory elements controlling I177L protein expression, resulting in a non-functional genomic I177L gene. This mutant virus genome has at least 95% identity to SEQ ID NO: 2, representing the ASFV-GΔI177L mutant.
The claims essentially cover the genetically engineered ASFV-GΔI177L virus with the I177L gene rendered nonfunctional, vaccine compositions comprising such virus targeting ASFV-Georgia 2007 isolate, and methods of protecting swine by administering these live attenuated vaccines.
Stated Advantages
The vaccine produced by deletion of the I177L gene results in complete attenuation of the highly virulent ASFV-G strain, preventing clinical signs and lethality upon infection.
Vaccination with ASFV-GΔI177L induces protective immunity against challenge with the virulent parental ASFV-G virus in swine.
The mutant virus retains the ability to replicate, though at reduced levels compared to parental virus, allowing immune response stimulation without causing disease.
The live attenuated vaccine virus is not shed sufficiently by infected animals to infect cohabitating naive animals, enhancing biosafety.
Vaccinated animals develop robust antibody responses (IgM and IgG), correlating with protection, and sterile immunity is achievable at sufficient vaccine doses.
Documented Applications
Use as a live attenuated vaccine to protect domestic and wild swine from African Swine Fever caused by ASFV strains including the highly virulent ASFV Georgia 2007 isolate.
Methods for vaccination of swine by administering the ASFV-GΔI177L live attenuated vaccine intramuscularly or by other routes to induce protective immunity.
Differentiation of infected from vaccinated animals (DIVA) using serological or molecular techniques to distinguish vaccine virus from wild-type ASFV infection.
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