Jiangnan Li #,Jie Song #,Shijun Zhou,Shuai Li,Jia Liu,Tingting Li,Zhaoxia Zhang,Xianfeng Zhang,Xijun He,Weiye Chen,Jun Zheng,Dongming Zhao,Zhigao Bu,Li Huang,Changjiang Weng

J Virol. 2023 Sep 28:e0070423.doi: 10.1128/jvi.00704-23

Abstract

African swine fever is a contagious and lethal disease of domestic pigs and wild boars, which has caused significant economic loss for the swine industry. African swine fever virus (ASFV) is the etiological agent of ASF. Until now, no effective commercial vaccine and antiviral drugs are available for ASF control. Here, we report a new designed live-attenuated mutant (ASFV-ΔH240R-Δ7R) by deleting H240R and MGF505-7R genes based on the highly pathogenic ASFV HLJ/18 backbone. The viral titer of ASFV-ΔH240R-Δ7R was decreased approximately 1.0 log in porcine alveolar macrophages (PAMs) compared with its parental ASFV HLJ/18, and it is highly stability following 30 serial passages  in vitro . Piglets immunized by intramuscular inoculation with 10³ or 10⁵ HAD₅₀ of ASFV-ΔH240R-Δ7R displayed safety without any ASF-related signs and could not be transmitted by direct contact. In addition, the immunized pigs produced specific antibodies against p30 but not those cohabitation piglets. Challenged with a virulent ASFV isolate HLJ/18, the piglets in the immunized group with 10³ HAD₅₀ of ASFV-ΔH240R-Δ7R obtained clinically significant 100% protection with mild clinical symptoms, whereas the piglets in the immunized group with 10⁵ HAD₅₀ of ASFV-ΔH240R-Δ7R obtained 100% protection without clinical symptoms. Moreover, the piglets in the immunized group with 10⁵ HAD₅₀ of ASFV-ΔH240R-Δ7R exhibited low levels of virus replication and with no observed pathological changes by postmortem and histological analysis. Overall, our results provided a new designed live vaccine candidate and rationalized the understanding of ASFV gene function, virus attenuation, and protection against ASFV infection. IMPORTANCE African swine fever (ASF) caused by ASF virus (ASFV) is a highly contagious and acute hemorrhagic viral disease in domestic pigs. Until now, no effective commercial vaccine and antiviral drugs are available for ASF control. Here, we generated a new live-attenuated vaccine candidate (ASFV-ΔH240R-Δ7R) by deleting H240R and MGF505-7R genes from the highly pathogenic ASFV HLJ/18 genome. Piglets immunized with ASFV-ΔH240R-Δ7R were safe without any ASF-related signs and produced specific antibodies against p30. Challenged with a virulent ASFV HLJ/18, the piglets immunized with high-dose group (105 HAD50) exhibited 100% protection without clinical symptoms, showing that low levels of virus replication with no observed pathogenicity by postmortem and histological analysis. Overall, our results provided a new strategy by designing live-attenuated vaccine candidate, resulting in protection against ASFV infection.

Keywords: ASFV; H240R; MGF505-7R; attenuation; protective efficacy.