Abstract
Fowl typhoid (FT) poses a significant threat to the poultry industry, especially in developing regions, causing substantial economic losses. Caused by Salmonella Gallinarium, FT can be prevented by vaccination, but existing vaccines like the SG9R strain have limitations, including residual virulence and potential reversion of pathogenicity. This study aims to develop safer and more effective SG vaccine strains through targeted genetic modifications, focusing on genes involved in lipopolysaccharide (LPS) biosynthesis and modification. We evaluated two novel mutant SG strains, JOL3015 and JOL3016, carrying in-frame deletions in ΔlonΔrfaLΔarnT and ΔlonΔrfaLΔpagL respectively. Intramuscular immunization with JOL3015 and JOL3016 strains showed minimal impact on the growth of 4-week-old young birds, significantly increased antigen-specific IgY, sIgA secretion, and CD4+ and CD8+ T cell responses, while inducing lower proinflammatory cytokine levels than SG9R. Histopathological evaluations revealed substantial protection in immunized birds, with minimal tissue damage and inflammatory responses, reducing the in vivo bacterial burden. None of the immunized birds died, highlighting the significant safety and protection conferred by the selected genetic modifications. Our results indicate that JOL3016 provided comparable protective outcomes on par with SG9R, yet with significantly lower endotoxicity responses during the lethal challenge with SG WT JOL422. The novel detoxified SG strains, particularly JOL3016, offer a promising alternative to existing vaccines for FT. They provide effective protection with minimal impact on poultry growth, minimizing the risks associated with reversion and endotoxicity. This study highlights the potential of genetically engineered vaccine strains in improving poultry health and productivity, emphasizing the importance of continued research.