ABSTRACT

African swine fever (ASF) is a lethal and highly contagious viral disease of domestic and wild pigs, listed as a notifiable disease reported to the World Organization for Animal Health (OIE). Despite its limited host range and absent zoonotic potential, the socio-economic and environmental impact of ASF is very high, representing a serious threat to the global swine industry and the many stakeholders involved. Currently, only control and eradication measures based mainly on early detection and strict stamping-out policies are available, however, the rapid spread of the disease in new countries, and in new regions in countries already affected, show these strategies to be lacking. In this review, we discuss approaches to ASF vaccinology, with emphasis on the advances made over the last decade, including the development of virulence-associated gene deleted strains such as the very promising ASFV-G-ΔI177L/ΔLVR, that replicates efficiently in a stable porcine epithelial cell line, and the cross-protecting BA71ΔCD2 capable of stably growing in the commercial COS-1 cell line, or the naturally attenuated Lv17/WB/Rie1 which shows solid protection in wild boar. We also consider the key constraints involved in the scale-up and commercialization of promising live attenuated and virus-vectored vaccine candidates, namely cross-protection, safety, lack of suitable animal models, compatibility with wildlife immunization, availability of established and licensed cell lines, and differentiating infected from vaccinated animals (DIVA) strategy.

摘要

非洲猪瘟（ASF）是一种致命的、高度传染性的家猪和野猪病毒性疾病，被列为世界动物卫生组织（OIE）报告的法定传染病。尽管宿主范围有限且缺乏人畜共患潜力，但 ASF 的社会经济和环境影响非常高，对全球养猪业和许多相关利益相关者构成严重威胁。目前，只有以早期发现和严格的扑灭政策为主的控制和根除措施可用，然而，该疾病在新国家和已受影响国家的新地区迅速传播，表明这些策略缺乏。在这篇综述中，我们讨论了 ASF 疫苗学的方法，重点是过去十年取得的进展，包括开发毒力相关基因缺失菌株，例如非常有前途的 ASFV-G-ΔI177L/ΔLVR，可在稳定的猪上皮细胞系中有效复制，以及能够在商业 COS-1 中稳定生长的交叉保护 BA71ΔCD2细胞系，或自然减毒的 Lv17/WB/Rie1，在野猪中表现出坚实的保护作用。我们还考虑了有希望的减毒活疫苗和病毒载体候选疫苗的放大和商业化的关键限制，即交叉保护、安全性、缺乏合适的动物模型、与野生动物免疫的兼容性、已建立和许可的细胞系的可用性，以及区分感染和接种动物 (DIVA) 策略。在稳定的猪上皮细胞系中有效复制，以及能够在商业 COS-1 细胞系中稳定生长的交叉保护 BA71ΔCD2，或在野猪中显示出可靠保护的自然减毒 Lv17/WB/Rie1。我们还考虑了有希望的减毒活疫苗和病毒载体候选疫苗的放大和商业化的关键限制，即交叉保护、安全性、缺乏合适的动物模型、与野生动物免疫的兼容性、已建立和许可的细胞系的可用性，以及区分感染和接种动物 (DIVA) 策略。在稳定的猪上皮细胞系中有效复制，以及能够在商业 COS-1 细胞系中稳定生长的交叉保护 BA71ΔCD2，或在野猪中显示出可靠保护的自然减毒 Lv17/WB/Rie1。我们还考虑了有希望的减毒活疫苗和病毒载体候选疫苗的放大和商业化的关键限制，即交叉保护、安全性、缺乏合适的动物模型、与野生动物免疫的兼容性、已建立和许可的细胞系的可用性，以及区分感染和接种动物 (DIVA) 策略。