Abstract :
[en] African swine fever (ASF) is a viral disease caused by African swine fever virus (ASFV), which leads high mortality in domestic pigs and wild boar. The occurrence of ASFV in affected countries often provokes severe economic losses and ecological consequences. Lack of knowledge concerning the diversity of ASFV strains and the puzzling virus-host interactions involved in infection and immunity hinders the development of vaccines and complicates the control and eradication of ASF. Currently, there is no commercially available vaccine. In recent years, the prevalence of ASFV makes it urgent to acquire more knowledge and tools for protection against ASFV. In this thesis, we discussed the prevention of ASF from the following three aspects: immune evasion mechanism, vaccine development, and adjuvant for animal vaccine.
Firstly, we demonstrated the action mechanism of DP96R gene of ASFV, which is one of the viral virulence factors. Results showed that DP96R of ASFV China2018/1 strain blocks the cytosolic cGAS-STING-TBK1 signaling pathway by inhibiting the activation of both TBK1 and IKKβ, thus down-regulating the expression of type I IFNs and inflammatory cytokines. This provides insightful information for further investigation to better understand the mechanism of immune evasion of ASFV.
Secondly, we utilized dual expression vector to construct recombinant DNA plasmids encoding ASFV main structural genes, B646L (p72), E183L (p54), CP204L (p30), EP402R (CD2v) respectively, and genetic adjuvants (IRF3-5D, TBK1), then evaluated the induced immune responses following the administration of the DNA cocktail vaccines in mice. The results suggested ASFV DNA cocktail vaccines based on appropriate antigen genes and TBK1 as a genetic adjuvant offer a promising strategy for the development of ASFV vaccines.
Thirdly, the action mechanism of new animal vaccine adjuvant pUC18-CpG was investigated. It stimulates RAW 264.7 mainly through the TBK1-mediated signaling pathway, causing the up-regulation of interferons and pro-inflammatory cytokines. It showed great adjuvanticity in mice and induced antigen-specific cytokine expression towards a Th1 based immune response. A better understanding of the pUC18-CpG is helpful for the promotion of its clinical application.
In conclusion, we revealed a new immune evasion mechanism of ASFV, constructed a new type of ASFV DNA vaccine, and deepened our understanding of animal vaccine adjuvant (pUC18-CpG), which will provide theoretical knowledge and technical support for the prevention and control of ASF.
