Combination of trained immunity and specific inactivated vaccine against S. Choleraesuis infection in pigs.

INTRODUCTION: Salmonella enterica subsp. enterica serovar Choleraesuis is a pathogen that can cause severe systemic disease and remains a challenge in swine production due to its impact on animal health, economic losses, and zoonotic risk. While vaccination is a key control tool, current vaccines often provide limited protection to the targeted (and untargeted) serovar. Trained immunity has gained attention as a possible way to enhance non-specific protection. METHODS: This study explored whether a porcine-derived BCG strain (dpB), administered live or inactivated, could improve the protective effect of a conventional S. Choleraesuis vaccine in pigs, not only against homologous challenge but also against heterologous serovars. RESULTS: Pigs immunized with inactivated dpB in conjunction with the S. Choleraesuis vaccine showed a trend toward better bacterial control, with the lowest levels of S. Choleraesuis recovered from feces and ileocecal lymph nodes. Additionally, this group demonstrated a slight improved immune reactivity to heterologous serovars and a balanced cytokine response, without indications of excessive inflammation. In contrast, animals that received live dpB in addition to the vaccine showed the most severe pulmonary lesions, lowest phagocytic activity and a dysregulated cytokine profile. DISCUSSION: These results suggest that inactivated dpB may modulate immune responses when administered together with a conventional S. Choleraesuis vaccine and could contribute to improved bacterial control. However, the observed effects were generally modest and require confirmation in larger studies. These preliminary results support further investigation of trained immunity-based approaches as potential strategies added to conventional vaccination against Salmonella in swine.