摘要:SummaryAquaculture provides important food, nutrition, and income sources for humans. However, aquaculture industry is seriously threatened by viral diseases. Infectious spleen and kidney necrosis virus (ISKNV) disease causes high mortality and economic losses to the fish culture industry in Asia and has been listed as a certifiable disease by the International Epizootic Office. Vaccine development is urgent to control this disease. Here, a gene-deleted live attenuated candidate vaccine (ΔORF022L) against ISKNV with low pathogenicity and high protection was developed. ΔORF022L replicated well in mandarin fish fry-1 cells and showed similar structure with wild-type ISKNV. However, the pathogenicity was significantly lower as 98% of the mandarin fish infected with ΔORF022L survived, whereas all those infected with wild-type ISKNV died. Of importance, 100% of the ΔORF022L-infected fish survived the ISKNV challenge. ΔORF022L induced anti-ISKNV specific antibody response and upregulation of immune-related genes. This work could be beneficial to the control of fish diseases.Graphical abstractDisplay OmittedHighlights•ISKNV ORF022L deletion recombinant virus (ΔORF022L) was constructed•ΔORF022L was greatly attenuated and caused only 2% mortality in mandarin fish•ΔORF022L-immunized mandarin fish were 100% protected from ISKNV challenge•ORF022L induced immune-related genes and ISKNV-specific antibody responsesVirology; Aquaculture diseases