<i>Leptospira</i> –host interactions: advancing next-generation vaccines and diagnostics

SUMMARY Leptospirosis, a widespread zoonotic disease caused by pathogenic Leptospira species, remains a major public health challenge, particularly in tropical and subtropical regions. Despite advances in understanding Leptospira biology and pathogenesis, effective disease control continues to be limited by the lack of rapid, early diagnostics, and broadly protective vaccines. This review comprehensively examines recent progress in deciphering Leptospira –host interactions, with emphasis on key virulence factors, immune-evasion mechanisms, and host immune responses that influence disease outcomes. Particular focus is placed on the molecular and cellular basis of adhesion, invasion, immune modulation, and persistent colonization. We further discuss the limitations of current vaccines and diagnostic approaches, and highlight how emerging technologies, including pan-genomics, proteomics, reverse vaccinology, immunoinformatics, and omics-based antigen discovery, are facilitating the development of next-generation vaccines and diagnostics. Finally, we outline major translational challenges and future perspectives for improving clinical management, surveillance, and prevention of leptospirosis. The concepts discussed in this review may also provide broader insights into vaccine and diagnostic development for other zoonotic bacterial infections.