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Development of a highly effective African swine fever virus vaccine by deletion of the I177L gene results in sterile immunity against the current epidemic Eurasia strain

Manuel V. Borca, Elizabeth Ramirez Medina, Ediane Silva, Elizabeth Vuono, Ayushi Rai, Sarah Pruitt, Lauren G. Holinka, Lauro Velazquez Salinas, James Zhu, Douglas P. Gladue
doi: https://doi.org/10.1101/861666
Manuel V. Borca
1Agricultural Research Service, U.S. Department of Agriculture, Plum Island Animal Disease Center, Greenport, NY 11944, USA
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  • For correspondence: manuel.borca@ars.usda.gov douglas.gladue@ars.usda.gov
Elizabeth Ramirez Medina
1Agricultural Research Service, U.S. Department of Agriculture, Plum Island Animal Disease Center, Greenport, NY 11944, USA
2Department of Pathobiology and Veterinary Science, University of Connecticut, Storrs, CT 06269, USA
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Ediane Silva
1Agricultural Research Service, U.S. Department of Agriculture, Plum Island Animal Disease Center, Greenport, NY 11944, USA
3Department of Anatomy and Physiology, Kansas State University, Manhattan, KS 66506
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Elizabeth Vuono
1Agricultural Research Service, U.S. Department of Agriculture, Plum Island Animal Disease Center, Greenport, NY 11944, USA
4Department of Pathobiology and Population Medicine, Mississippi State University, P.O. Box 6100, MS 39762
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Ayushi Rai
1Agricultural Research Service, U.S. Department of Agriculture, Plum Island Animal Disease Center, Greenport, NY 11944, USA
5Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN 37830, USA
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Sarah Pruitt
1Agricultural Research Service, U.S. Department of Agriculture, Plum Island Animal Disease Center, Greenport, NY 11944, USA
5Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN 37830, USA
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Lauren G. Holinka
1Agricultural Research Service, U.S. Department of Agriculture, Plum Island Animal Disease Center, Greenport, NY 11944, USA
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Lauro Velazquez Salinas
1Agricultural Research Service, U.S. Department of Agriculture, Plum Island Animal Disease Center, Greenport, NY 11944, USA
3Department of Anatomy and Physiology, Kansas State University, Manhattan, KS 66506
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James Zhu
1Agricultural Research Service, U.S. Department of Agriculture, Plum Island Animal Disease Center, Greenport, NY 11944, USA
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Douglas P. Gladue
1Agricultural Research Service, U.S. Department of Agriculture, Plum Island Animal Disease Center, Greenport, NY 11944, USA
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  • For correspondence: manuel.borca@ars.usda.gov douglas.gladue@ars.usda.gov
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Abstract

African swine fever virus (ASFV) is the etiological agent of a contagious and often lethal disease of domestic pigs that has significant economic consequences for the swine industry. The disease is devastating the swine industry in Central Europe and East Asia, with current outbreaks caused by circulating strains of ASFV derived from the 2007 Georgia isolate (ASFV-G), a genotype II ASFV. In the absence of any available vaccines, African Swine Fever (ASF) outbreak containment relies on control and culling of infected animals. Limited cross protection studies suggest that in order to ensure a vaccine is effective it must be derived from the current outbreak strain or at the very least from an isolate with the same genotype. Here we report the discovery that deletion of a previously uncharacterized gene, I177L, from the highly virulent ASFV-G produces complete virus attenuation in swine. Animals inoculated intramuscularly with the virus lacking the I177L gene, ASFV-G-ΔI177L, in a dose range of 102 to 106 HAD50 remained clinically normal during the 28 day observational period. All ASFV-G-ΔI177L-infected animals had low viremia titers, showed no virus shedding, developed a strong virus-specific antibody response and, importantly, they were protected when challenged with the virulent parental strain ASFV-G. ASFV-G-ΔI177L is one of the few experimental vaccine candidate virus strains reported to be able to induce protection against the ASFV Georgia isolate, and the first vaccine capable of inducing sterile immunity against the current ASFV strain responsible for recent outbreaks.

Importance Currently there is no commercially available vaccine against African swine fever. Outbreaks of this disease are devastating the swine industry from Central Europe to East Asia, and they are being caused by circulating strains of African swine fever virus derived from the Georgia2007 isolate. Here we report the discovery of a previously uncharacterized virus gene, which when deleted completely attenuates the Georgia isolate. Importantly, animals infected with this genetically modified virus were protected from developing ASF after challenge with the virulent parental virus. Interestingly, ASFV-G-ΔI177L confers protection even at low doses (102 HAD50) and remains completely attenuated when inoculated at high doses (106 HAD50), demonstrating its potential as a safe vaccine candidate. At medium doses (104 HAD50) sterile immunity is achieved. Therefore, ASFV-G-ΔI177L is a novel efficacious experimental ASF vaccine protecting pigs from the epidemiologically relevant ASFV Georgia isolate.

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Posted December 02, 2019.
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Development of a highly effective African swine fever virus vaccine by deletion of the I177L gene results in sterile immunity against the current epidemic Eurasia strain
Manuel V. Borca, Elizabeth Ramirez Medina, Ediane Silva, Elizabeth Vuono, Ayushi Rai, Sarah Pruitt, Lauren G. Holinka, Lauro Velazquez Salinas, James Zhu, Douglas P. Gladue
bioRxiv 861666; doi: https://doi.org/10.1101/861666
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Development of a highly effective African swine fever virus vaccine by deletion of the I177L gene results in sterile immunity against the current epidemic Eurasia strain
Manuel V. Borca, Elizabeth Ramirez Medina, Ediane Silva, Elizabeth Vuono, Ayushi Rai, Sarah Pruitt, Lauren G. Holinka, Lauro Velazquez Salinas, James Zhu, Douglas P. Gladue
bioRxiv 861666; doi: https://doi.org/10.1101/861666

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