Agricultural Research Service, U.S. Department of Agriculture, Plum Island Animal Disease Center, Greenport, New York, USA.
Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
J Virol. 2021 Oct 13;95(21):e0113921. doi: 10.1128/JVI.01139-21. Epub 2021 Aug 18.
African swine fever virus (ASFV) is causing a devastating pandemic in domestic and wild swine within an extended geographical area from Central Europe to East Asia, resulting in economic losses for the regional swine industry. There are no commercial vaccines; therefore, disease control relies on identification and culling of infected animals. We report here that the deletion of the ASFV gene A137R from the highly virulent ASFV-Georgia2010 (ASFV-G) isolate induces a significant attenuation of virus virulence in swine. A recombinant virus lacking the A137R gene, ASFV-G-ΔA137R, was developed to assess the role of this gene in ASFV virulence in domestic swine. Animals inoculated intramuscularly with 10 50% hemadsorption doses (HAD) of ASFV-G-ΔA137R remained clinically healthy during the 28-day observational period. All animals inoculated with ASFV-G-ΔA137R had medium to high viremia titers and developed a strong virus-specific antibody response. Importantly, all ASFV-G-ΔA137R-inoculated animals were protected when challenged with the virulent parental strain ASFV-G. No evidence of replication of challenge virus was observed in the ASFV-G-ΔA137R-inoculated animals. Therefore, ASFV-G-ΔA137R is a novel potential live attenuated vaccine candidate and one of the few experimental vaccine strains reported to induce protection against the highly virulent ASFV Georgia virus that is the cause of the current Eurasian pandemic. No commercial vaccine is available to prevent African swine fever. The ASF pandemic caused by ASFV Georgia2007 strain (ASFV-G) is seriously affecting pork production in a contiguous area from Central Europe to East Asia. Here we report the rational development of a potential live attenuated vaccine strain by deleting a virus-specific gene, A137R, from the genome of ASFV-G. The resulting virus presented a completely attenuated phenotype and, importantly, animals infected with this genetically modified virus were protected from developing ASF after challenge with the virulent parental virus. ASFV-G-ΔA137R confers protection even at low doses (10 HAD), demonstrating its potential as a vaccine candidate. Therefore, ASFV-G-ΔA137R is a novel experimental ASF vaccine protecting pigs from the epidemiologically relevant ASFV Georgia isolate.
非洲猪瘟病毒(ASFV)正在从中欧延伸到东亚的广大地理区域内,对家猪和野猪造成毁灭性的大流行,给该地区的养猪业造成了经济损失。目前没有商业疫苗;因此,疾病控制依赖于感染动物的识别和扑杀。我们在此报告,从高致病性 ASFV-Georgia2010(ASFV-G)分离株中删除 ASFV 的 A137R 基因可显著降低病毒在家猪中的毒力。开发了缺乏 A137R 基因的重组病毒 ASFV-G-ΔA137R,以评估该基因在家猪中 ASFV 毒力的作用。肌肉内接种 10 个 50%红细胞吸附剂量(HAD)的 ASFV-G-ΔA137R 的动物在 28 天观察期内保持临床健康。所有接种 ASFV-G-ΔA137R 的动物均具有中等至高的病毒血症滴度,并产生强烈的病毒特异性抗体反应。重要的是,所有接种 ASFV-G-ΔA137R 的动物在受到高致病性亲本株 ASFV-G 的攻毒时均受到保护。在接种 ASFV-G-ΔA137R 的动物中未观察到攻毒病毒的复制。因此,ASFV-G-ΔA137R 是一种新型潜在的减毒活疫苗候选物,也是少数报道可诱导针对引起当前欧亚大流行的高致病性 ASFV 格鲁吉亚病毒的保护作用的实验性疫苗株之一。目前尚无预防非洲猪瘟的商业疫苗。由 ASFV Georgia2007 株(ASFV-G)引起的 ASF 大流行严重影响了从中欧到东亚的连续地区的猪肉生产。在这里,我们报告了通过从 ASFV-G 的基因组中删除病毒特异性基因 A137R 来合理开发潜在的减毒活疫苗株。由此产生的病毒表现出完全减毒的表型,重要的是,感染这种基因修饰病毒的动物在用高致病性亲本病毒攻毒后可免于发生 ASF。ASFV-G-ΔA137R 即使在低剂量(10 HAD)下也能提供保护,证明了其作为疫苗候选物的潜力。因此,ASFV-G-ΔA137R 是一种新型的实验性 ASF 疫苗,可保护猪免受具有流行病学意义的 ASFV 格鲁吉亚分离株的侵害。