Evaluation of a Newly Developed Live Attenuated Vaccine Candidate Against Lawsonia intracellularis

<b>Background/Objectives</b>: <i>Lawsonia intracellularis</i> (<i>L. intracellularis</i>) is an important intestinal pathogen that causes porcine proliferative enteropathy (PPE) in swine production worldwide. Currently, only a few commercially available vaccines are available for PPE prevention. <b>Methods</b>: In this study, an attenuated <i>L. intracellularis</i> variant of JS-G90 was obtained through subculturing of <i>L. intracellularis</i> JS isolates in McCoy cells for 90 generations, and its immune response was evaluated in pigs. <b>Results</b>: The results demonstrated that pigs who underwent intragastric administration of JS-G90 had lower fecal bacterial shedding and no histopathological lesions, indicating that it was safe in pigs. Therefore, JS-G90 was selected to develop the attenuated PPE vaccine. The immune response of JS-G90 in pigs was further evaluated based on fecal bacterial shedding, histopathological lesions, and humoral and cell-mediated immune responses following challenge with pathogenic <i>L. intracellularis</i>. The results revealed that JS-G90 significantly decreased the copies of <i>L. intracellularis</i> in rectal swabs containing feces and ileum infection (<i>p</i> < 0.001), reduced histopathological lesions in the ileum, and elicited non-specific humoral (IgG and sIgA) and cell-mediated immune responses (<i>p</i> < 0.001) compared with the challenge control and mock groups. <b>Conclusions</b>: In conclusion, the attenuated vaccine JS-G90 is safe and induced humoral and cell-mediated immune responses in pigs against pathogenic <i>L. intracellularis</i> infection. It may serve as an effective strategy for preventing and controlling PPE.