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Life sciences · Journal article
Fish & Shellfish Immunology · October 8, 2026
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Bacterial infections caused by the intracellular bacterium Francisella noatunensis pose a major health challenge in Atlantic cod (Gadus morhua), largely due to the lack of effective prophylactic and therapeutic measures. Here, we evaluated the immune and physiological responses of cod to two candidate live attenuated vaccines (i.e. clpB and iglC) against F. noatunensis delivered intranasally. These experimental vaccines were constructed by a single knockout mutation of a virulence gene in F. noatunensis. Cod was vaccinated intranasally and reared for 45 days until infection with the wild-type strain Francisella noatunenesis subp. noatunensis and further reared for 47 days until termination. Given the chosen delivery route, our analyses were focused on the olfactory organ and brain of cod. Infected cod presented classic gross pathologies of francisellosis, including multi-organ nodulations, splenomegaly, and hepatomegaly. Among the vaccine candidates, the clpB-vaccinated group demonstrated upregulated expression of immune response genes in both the olfactory organ and brain, exhibited the lowest nodulation score, and showed minimal histological alterations in the olfactory organ. To further explore the physiological consequences of the clpB mutant, shotgun proteomics was performed in selected olfactory organ and brain of vaccinated cod. We identified 404 differentially expressed proteins (DEPs) in the brain and 241 in the olfactory organ with 17 DEPs common to both organs. These DEPs were mostly involved in cellular signalling, transmembrane internalisation, enzymatic processes, and key immune response pathways, such as immune recruitment and activation, the respiratory burst reaction, and apoptosis. These findings suggest that the clpB-attenuated vaccine holds promise as a candidate vaccine against F. noatunensis and provides valuable insights into the mechanisms of immune modulation.