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      ASFV-G-∆I177L as an Effective Oral Nasal Vaccine against the Eurasia Strain of Africa Swine Fever

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          Abstract

          The African swine fever virus (ASFV) is currently causing a pandemic affecting wild and domestic swine from Western Europe to Asia. No commercial vaccines are available to prevent African swine fever (ASF), resulting in overwhelming economic losses to the swine industry. We recently developed a recombinant vaccine candidate, ASFVG-ΔI177L, by deleting the I177L gene from the genome of the highly virulent ASFV strain Georgia (ASFV-G). ASFV-G-ΔI177L has been proven safe and highly efficacious in challenge studies using parental ASFV-G. Here, we present data demonstrating that ASFV-G-ΔI177L can be administered by the oronasal (ON) route to achieve a similar efficacy to that of intramuscular (IM) administration. Animals receiving ON ASFV-G-ΔI177L were completely protected against virulent ASFV-G challenge. As previously described, similar results were obtained when ASFV-G-ΔI177L was given intramuscularly. Interestingly, viremias induced in animals inoculated oronasally were lower than those measured in IM-inoculated animals. ASFV-specific antibody responses, mediated by IgG1, IgG2 and IgM, do not differ in animals inoculated by the ON route from that had IM inoculations. Therefore, the ASFV-G-ΔI177L vaccine candidate can be administered oronasally, a critical attribute for potential vaccination of wild swine populations.

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          African swine fever: how can global spread be prevented?

          African swine fever (ASF) is a devastating haemorrhagic fever of pigs with mortality rates approaching 100 per cent. It causes major economic losses, threatens food security and limits pig production in affected countries. ASF is caused by a large DNA virus, African swine fever virus (ASFV). There is no vaccine against ASFV and this limits the options for disease control. ASF has been confined mainly to sub-Saharan Africa, where it is maintained in a sylvatic cycle and/or among domestic pigs. Wildlife hosts include wild suids and arthropod vectors. The relatively small numbers of incursions to other continents have proven to be very difficult to eradicate. Thus, ASF remained endemic in the Iberian peninsula until the mid-1990s following its introductions in 1957 and 1960 and the disease has remained endemic in Sardinia since its introduction in 1982. ASF has continued to spread within Africa to previously uninfected countries, including recently the Indian Ocean islands of Madagascar and Mauritius. Given the continued occurrence of ASF in sub-Saharan Africa and increasing global movements of people and products, it is not surprising that further transcontinental transmission has occurred. The introduction of ASF to Georgia in the Caucasus in 2007 and dissemination to neighbouring countries emphasizes the global threat posed by ASF and further increases the risks to other countries. We review the mechanisms by which ASFV is maintained within wildlife and domestic pig populations and how it can be transmitted. We then consider the risks for global spread of ASFV and discuss possibilities of how disease can be prevented.
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            A seven-gene-deleted African swine fever virus is safe and effective as a live attenuated vaccine in pigs

            African swine fever (ASF) is a devastating infectious disease in swine that is severely threatening the global pig industry. An efficacious vaccine is urgently required. Here, we used the Chinese ASFV HLJ/18 as a backbone and generated a series of gene-deleted viruses. The virulence, immunogenicity, safety, and protective efficacy evaluation in specific-pathogen-free pigs, commercial pigs, and pregnant sows indicated that one virus, namely HLJ/18-7GD, which has seven genes deleted, is fully attenuated in pigs, cannot convert to the virulent strain, and provides complete protection of pigs against lethal ASFV challenge. Our study shows that HLJ/-18-7GD is a safe and effective vaccine against ASFV, and as such is expected to play an important role in controlling the spread of ASFV. Electronic Supplementary Material Supplementary material is available for this article at 10.1007/s11427-020-1657-9 and is accessible for authorized users.
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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.

              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 10 2 to 10 6 HAD 50 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 (10 2 HAD 50 ) and remains completely attenuated when inoculated at high doses (10 6 HAD 50 ), demonstrating its potential as a safe vaccine candidate. At medium or higher doses (10 4 HAD 50 ) 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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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Viruses
                Viruses
                viruses
                Viruses
                MDPI
                1999-4915
                27 April 2021
                May 2021
                : 13
                : 5
                : 765
                Affiliations
                [1 ]Plum Island Animal Disease Center, ARS, USDA, Greenport, NY 11944, USA; Elizabeth.Ramirez@ 123456usda.gov (E.R.-M.); Ediane.Silva@ 123456usda.gov (E.S.); Elizabeth.Vuono@ 123456usda.gov (E.V.); ayushi.rai@ 123456usda.gov (A.R.); Sarah.Pruitt@ 123456usda.gov (S.P.); Nallely.Espinoza@ 123456usda.gov (N.E.); Lauro.Velazquez@ 123456usda.gov (L.V.-S.)
                [2 ]Department of Anatomy and Physiology, Kansas State University, Manhattan, KS 66506, USA
                [3 ]Department of Pathobiology and Population Medicine, Mississippi State University, P.O. Box 6100, Starkville, MS 39762, USA
                [4 ]Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN 37830, USA
                [5 ]Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705, USA; Cyril.Gay@ 123456usda.gov
                Author notes
                [* ]Correspondence: Manuel.Borca@ 123456usda.gov (M.V.B); Douglas.Gladue@ 123456usda.gov (D.P.G.); Tel.: +631-323-3131 (M.V.B.); +631-323-3035 (D.P.G.)
                Author information
                https://orcid.org/0000-0002-7894-0233
                Article
                viruses-13-00765
                10.3390/v13050765
                8146859
                33925435
                5db290bf-bc71-40be-b2d8-144168356fba
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 02 April 2021
                : 25 April 2021
                Categories
                Article

                Microbiology & Virology
                asfv,i177l,african swine fever,asf,african swine fever virus,vaccine,swine
                Microbiology & Virology
                asfv, i177l, african swine fever, asf, african swine fever virus, vaccine, swine

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