title: African swine fever virus Georgia isolate harboring deletions of 9GL and MGF360/505 genes is highly attenuated in swine but does not confer protection against parental virus challenge.
abstract: African swine fever virus (ASFV) produces a contagious disease of domestic pigs that results in severe economic consequences to the swine industry. Control of the disease has been hampered by the unavailability of vaccines. We recently reported the development of two experimental vaccine strains (ASFV-G-Δ9GL and ASFV-G-ΔMGF) based on the attenuation of the highly virulent and epidemiologically relevant Georgia2007 isolate. Deletion of the 9GL gene or six genes of the MGF360/505 group produced two attenuated ASFV strains which were able to confer protection to animals when challenged with the virulent parental virus. Both viruses, although efficient in inducing protection, present concerns regarding their safety. In an attempt to solve this problem we developed a novel virus strain, ASFV-G-Δ9GL/ΔMGF, based on the deletion of all genes deleted in ASFV-G-Δ9GL and ASFV-G-ΔMGF. ASFV-G-Δ9GL/ΔMGF is the first derivative of a highly virulent ASFV field strain subjected to a double round of recombination events seeking to sequentially delete specific genes. ASFV-G-Δ9GL/ΔMGF showed a decreased ability to replicate in primary swine macrophage cultures relative to that of ASFV-G and ASFV-G-ΔMGF but similar to that of ASFV-G-Δ9GL. ASFV-G-Δ9GL/ΔMGF was attenuated when intramuscularly inoculated into swine, even at doses as high as 10(6) HAD50. Animals infected with doses ranging from 10(2) to 10(6) HAD50 did not present detectable levels of virus in blood at any time post-infection and they did not develop detectable levels of anti-ASFV antibodies. Importantly, ASFV-G-Δ9GL/ΔMGF does not induce protection against challenge with the virulent parental ASFV-G isolate. Results presented here suggest caution towards approaches involving genomic manipulations when developing rationally designed ASFV vaccine strains.
authors.affiliation: Agricultural Research Service, Plum Island Animal Disease Center, Greenport, NY 11944, USA; Department of Pathobiology and Veterinary Science, University of Connecticut, Storrs, CT 06269, USA.
authors.forename: Vivian
authors.initials: V
authors.lastname: O'Donnell
authors.affiliation: Agricultural Research Service, Plum Island Animal Disease Center, Greenport, NY 11944, USA.
authors.forename: Lauren G
authors.initials: LG
authors.lastname: Holinka
authors.affiliation: Department of Homeland Security, Plum Island Animal Disease Center, Greenport, NY 11944, USA.
authors.forename: Brenton
authors.initials: B
authors.lastname: Sanford
authors.affiliation: Agricultural Research Service, Plum Island Animal Disease Center, Greenport, NY 11944, USA.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Krug
authors.affiliation: Agricultural Research Service, Plum Island Animal Disease Center, Greenport, NY 11944, USA; Biosecurity Research Institute and Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA.
authors.forename: Jolene
authors.initials: J
authors.lastname: Carlson
authors.affiliation: Department of Homeland Security, Plum Island Animal Disease Center, Greenport, NY 11944, USA.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Pacheco
authors.affiliation: Center for Genome Innovation CAHNR, University of Connecticut, Storrs, CT 06269, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Reese
authors.affiliation: Department of Pathobiology and Veterinary Science, University of Connecticut, Storrs, CT 06269, USA.
authors.forename: Guillermo R
authors.initials: GR
authors.lastname: Risatti
authors.affiliation: Agricultural Research Service, Plum Island Animal Disease Center, Greenport, NY 11944, USA.
authors.forename: Douglas P
authors.initials: DP
authors.lastname: Gladue
authors.affiliation: Agricultural Research Service, Plum Island Animal Disease Center, Greenport, NY 11944, USA. Electronic address: manuel.borca@ars.usda.gov.
authors.forename: Manuel V
authors.initials: MV
authors.lastname: Borca
mesh_terms: D000357:African Swine Fever / Q000473:pathology* / Q000517:prevention & control / Q000821:virology*; D000358:African Swine Fever Virus / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity* / Q000502:physiology; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002478:Cells, Cultured; D005845:Georgia; D007273:Injections, Intramuscular; D008264:Macrophages / Q000821:virology; D011995:Recombination, Genetic; D017384:Sequence Deletion; D013552:Swine; D016896:Treatment Outcome; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014774:Virulence; D014779:Virus Replication
chemical_list: C403418:9GL protein, African swine fever virus; D000914:Antibodies, Viral; D014613:Vaccines, Attenuated; D014764:Viral Proteins; D014765:Viral Vaccines