Feng Tao, Zheng Dongdong, Zheng Linlin, Qi Xiaolan, Ren Jingjing, Ma Zhao, Liu Huanan, Shen Chaochao, Ru Yi, Li Dan, Tian Hong, Wu Sen, Zheng Haixue
State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.
State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.
FASEB J. 2025 May 31;39(10):e70638. doi: 10.1096/fj.202401462RR.
African swine fever virus (ASFV) poses a serious risk to wild boars and domestic pigs worldwide. Developing live-attenuated 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-GS-Δ7R/ΔI267L, with deletions of genes MGF505-7R and I267L, using the highly pathogenic parental strain ASFV-GS/2018 (ASFV-GS). In vitro, the viral titer of ASFV-GS-Δ7R/ΔI267L was approximately 10 times lower than that of its parental strain. Pigs inoculated with 10 50% hemadsorption doses (HAD) 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 HAD of virulent ASFV-GS, five of seven pigs in the immunization group remained disease-free, whereas seven pigs in the control group developed severe fever and died within 9 days 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 IL1B1 and CSF3 were significantly upregulated in ASFV mutant-infected porcine alveolar macrophages, but not in parental virus-infected macrophages. These findings provide important information for the development of ASF LAVs.
非洲猪瘟病毒（ASFV）对全球范围内的野猪和家猪构成严重威胁。开发含有特定基因缺失的减毒活疫苗（LAV）是预防和控制非洲猪瘟（ASF）疫情的有效方法。我们使用高致病性亲本菌株ASFV-GS/2018（ASFV-GS）创建了一种新型的ASFV突变体ASFV-GS-Δ7R/ΔI267L，该突变体缺失了基因MGF505-7R和I267L。在体外，ASFV-GS-Δ7R/ΔI267L的病毒滴度比其亲本菌株低约10倍。接种10个50%血细胞吸附剂量（HAD）该突变体的猪未出现ASF特有的严重发热和猝死症状。接种疫苗的猪血液中的病毒载量保持较低水平，且在免疫实验结束时体温趋于恢复正常。在用10个HAD的强毒ASFV-GS攻击后，免疫组的7头猪中有5头未发病，而对照组的7头猪在攻击后9天内出现严重发热并死亡。组织学检查显示，受保护的猪没有明显的病理损伤，且病毒载量低于未受保护的猪。此外，转录组分析表明，宿主基因IL1B1和CSF3在ASFV突变体感染的猪肺泡巨噬细胞中显著上调，但在亲本病毒感染的巨噬细胞中未上调。这些发现为ASF减毒活疫苗的开发提供了重要信息。
