Potential of inclusion bodies for disease control in aquaculture and livestock

Inclusion bodies are insoluble nanostructured recombinant proteins that have emerged as innovative biomaterials for disease control in animal production. This systematic literature review aimed to explore the use of inclusion bodies for disease control in aquaculture and livestock. We conducted a literature search in four databases: PubMed, Web of Science, ScienceDirect and Scopus. Of the 3139 research articles retrieved, only 16 met our eligibility criteria: 6 for aquaculture, including studies in rainbow trout, senegalese sole, and zebrafish, and 10 for livestock, including studies in cattle, sheep, swine, and mouse models. The proteins produced in these studies were mainly host immune system proteins and pathogen antigenic proteins. The diseases or pathogens potentially controlled by inclusion bodies in aquaculture were Pseudomonas aeruginosa, Mycobacterium marinum, Spring viremia of carp virus and Viral nervous necrosis virus. Conversely, the diseases or pathogens evaluated to be controlled by inclusion bodies in livestock were mastitis, Fasciola hepatica, Lawsonia intracellularis, and Vibrio sp. The administration strategies varied greatly, including intra-mammary gland infusion, nasal suspension, gastric injection, esophageal intubation, intramuscular injection, and oral administration. Regardless of administration route, these biomaterials consistently activated immune responses through two mechanisms: modulation of the host immune system via immunostimulatory proteins, and activation of adaptive immunity via antigenic proteins. Although promising, widespread adoption remains limited by technological challenges including purification standardization, batch variability, and lack of studies in commercially relevant species. These findings establish a robust evidence base to inform the development of IB-based interventions in animal health and guide future research directions.