Evaluation of trained immunity as a potential strategy for a universal Streptococcus suis vaccine using immunogenic proteins in a murine model

BACKGROUND: Universal vaccine against Streptococcus suis (S. suis) remains a challenge due to the high number of serotypes/strains, the absence of cross-protection among them and the existence of different immune escape strategies. In this study, the immunomodulatory potential of live and inactivated porcine derived Bacillus Calmette-Guérin (dpB) in combination with specific immunogenic proteins S. suis is evaluated in murine model. RESULTS: Results revealed different immune responses depending on dpB formulation. Live-dpB administered intravenously induced consistent results with trained immunity, including elevated proinflammatory cytokines and enhanced phagocytosis activity, reflecting stronger innate immune activation. However, inactivated dpB administered intravenously twice, enhanced adaptive responses post-S. suis vaccination showing increased IFN-γ levels in plasma and higher spot forming units in splenic ELISpot assays. DISCUSSION: These findings suggest complementary roles for live and inactivated dpB in innate and adaptive immunity. This approach may represent an initial step towards improving vaccine efficacy against S. suis, combining targeted innate with adaptive immunity. Further research is needed to optimize combinations of immunomodulators with traditional S. suis antigens.