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Developing live\u2010attenuated vaccines (LAVs) containing specific gene deletions is an effective approach to prevent and control African swine fever (ASF) epidemics. We created a novel ASFV mutant, ASFV\u2010GS\u2010\u03947R\/\u0394I267L, with deletions of genes\n                    <jats:italic>MGF505\u20107R<\/jats:italic>\n                    and\n                    <jats:italic>I267L<\/jats:italic>\n                    , using the highly pathogenic parental strain ASFV\u2010GS\/2018 (ASFV\u2010GS). In\u00a0vitro, the viral titer of ASFV\u2010GS\u2010\u03947R\/\u0394I267L was approximately 10 times lower than that of its parental strain. Pigs inoculated with 10\n                    <jats:sup>4<\/jats:sup>\n                    50% hemadsorption doses (HAD\n                    <jats:sub>50<\/jats:sub>\n                    ) of this mutant did not exhibit the severe fever and sudden death that are characteristic of ASF. The viral load in the blood of vaccinated pigs remained low, and their body temperatures tended to revert to normal at the end of the immunization experiment. After being challenged with 10\n                    <jats:sup>2<\/jats:sup>\n                    HAD\n                    <jats:sub>50<\/jats:sub>\n                    of virulent ASFV\u2010GS, five of seven pigs in the immunization group remained disease\u2010free, whereas seven pigs in the control group developed severe fever and died within 9\u2009days after the challenge. Histological examination revealed that the protected pigs showed no visible pathological damage and had lower viral loads than the unprotected pigs. Furthermore, transcriptome analysis demonstrated that the host genes\n                    <jats:italic>IL1B1<\/jats:italic>\n                    and\n                    <jats:italic>CSF3<\/jats:italic>\n                    were significantly upregulated in ASFV mutant\u2010infected porcine alveolar macrophages, but not in parental virus\u2010infected macrophages. These findings provide important information for the development of ASF LAVs.\n                  <\/jats:p>","DOI":"10.1096\/fj.202401462rr","type":"journal-article","created":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T07:10:28Z","timestamp":1747638628000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["<i>MGF505\u20107R<\/i>\n                    and\n                    <i>I267L<\/i>\n                    Deletions Attenuate African Swine Fever Virus and Confer Protection Against the Virulent Pandemic Virus in Pigs"],"prefix":"10.1096","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7824-7298","authenticated-orcid":false,"given":"Tao","family":"Feng","sequence":"first","affiliation":[{"name":"State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences  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