Astragalus polysaccharide inhibits infectious hematopoietic necrosis virus damage to rainbow trout (Oncorhynchus mykiss) spleen by promoting the efficacy of inactivated vaccine.

Pandemic infectious hematopoietic necrosis (IHN) caused by severe acute IHN virus (IHNV) threatens rainbow trout aquaculture in China. Therefore, it is crucial to develop effective vaccines and elucidate their mechanisms of action. Here, we revealed the mechanism of immune response of Astragalus polysaccharide (APS) combined with IHNV inactivated vaccine on rainbow trout spleen by serum enzyme activity assay, histopathological analysis, RNA-seq and viral load measurement. Histopathology and TUNEL showed that the APS combination vaccine significantly inhibited spleen damage and apoptosis by IHNV. Also, APS increased serum SOD, CAT, T-AOC, AKP and ACP activities by enhancing vaccine efficacy. Transcriptome analysis of the spleen showed that immune-related pathways were significantly enriched in the APS + vaccine group. The PPI network identified hub genes including IgM, IRF7, IgT, IgD, TLR7, CD4, CD8, IL-1β, and the APS + vaccine induced expression of these genes in the spleen. Notably, the APS combination vaccine significantly inhibited IHNV replication in the spleen. Overall, APS enhanced IHNV inactivated vaccine efficacy through stronger immune stimulation. These results indicate that the combined use of inactivated vaccine and APS can stimulate strong immunity in rainbow trout spleen, which provides valuable reference data to study the mechanism of aquatic vaccine immunoprophylaxis.