Immune sensing of DNA and strategies for fish DNA vaccine development

Studies of DNA vaccines have shown that understanding the mechanism of DNA vaccine-mediated action is the key for vaccine development. Current knowledge has shown the presence of antigen presenting cells (APCs) involving in B and T cells at the muscle injection site and the upregulation of type I interferon (IFN-I) that initiates antiviral response and benefits adaptive immunity in fish DNA vaccines. IFN-I may be triggered by expressed antigen such as the rhabdovirus G protein encoded DNA vaccine or by plasmid DNA itself through cytosolic DNA sensing. The investigating of Toll-like receptor 9, and 21 are the CpG-motif sensors in many fish species, and the cytosolic DNA receptors DDX41 and downstream STING signaling revealed the mechanisms for IFN-I production. This review article describes the recent finding of receptors for cytosolic DNA, the STING-TBK1-IRF signaling, and the possibility of turning these findings into strategies for the future development of DNA vaccines.