IL-11 acts as a vaccine adjuvant in Nile tilapia (Oreochromis niloticus) against Streptococcus agalactiae, enhancing both cellular and humoral immune responses.

Nile tilapia (Oreochromis niloticus) has become one of the most economically valuable fish species in global aquaculture. Recently, the industry has been increasingly affected by bacterial infections, particularly Streptococcus agalactiae, which has become a dominant pathogen causing severe disease outbreaks and economic losses. Interleukin (IL)-11 is a versatile cytokine involved in immune modulation, but its adjuvant potential has been rarely studied in fish. In this study, recombinant Nile tilapia IL-11 (rIL-11) was evaluated as a molecular adjuvant by co-injecting it with a formalin-killed whole-cell (FKC) S. agalactiae vaccine. Fish were divided into three groups: PBS (control), FKC alone, and FKC + rIL-11. Co-injection with rIL-11 significantly enhanced both innate and adaptive immune responses. Fish receiving FKC + rIL-11 showed significantly higher lysozyme, myeloperoxidase, glutathione peroxidase, and glutathione reductase activity compared to controls. Moreover, significantly increased IgM antibody levels were detected at all sampling points post-vaccination in the FKC + rIL-11 group, together with higher densities of IgM+ B cells in the spleen. Importantly, cytokine gene expression analysis revealed significant upregulation of TNF-α, IL-6, IL-8, IL-1β, IL-11a, and IL-11b in the spleen, and TNF-α and IL-8 in the liver, particularly during the early phase (days 1-3). Protective efficacy testing showed that the FKC + rIL-11 group achieved a relative percent survival (RPS) of 78.78 %, significantly higher than the 60.60 % observed with FKC alone. Overall, these results demonstrate that rIL-11 serves as a potent vaccine adjuvant, enhancing both humoral and cellular responses, and improving protection of Nile tilapia against S. agalactiae.