Leptospiral LigA-C mRNA-based immunization protects against Leptospira interrogans Serovar Australis infection

Abstract Leptospirosis, caused by the pathogenicLeptospira species, is one of the most prevalent zoonotic infections worldwide. Developing effective diagnostics and vaccines remains a critical challenge in combating this disease. Traditional bacterin-based vaccines have notable limitations, including short-lived immunity and serovar specificity. This study evaluated the leptospiral immunoglobulin-like protein A (LigA-C) as a vaccine candidate, focusing on its ability to elicit protective immune responses against leptospirosis. Using a hamster model, we demonstrated the protective efficacy of LigA-C mRNA immunization and explored the underlying immune mechanisms.LigA-C/mRNA immunization induced a robust antibody response, with significant increases observed following booster doses. Cytokine profiling revealed that elevated levels of IL-4, TNF-α, and IFN-γ were positively correlated with survival in immunized hamsters, while IL-10 levels were inversely correlated with protection. Immunized groups achieved 100% survival and exhibited minimal histopathological lesions in the kidneys and lungs. In contrast, control animals succumbed to infection within 11–15 days post-challenge with Leptospira interrogans serovar Australis strain Ballico.These findings indicate that LigA-C mRNA immunization confers protection through both humoral and cellular immune responses. The high survival rate and reduced pathology highlight the potential of LigA-C mRNA as a promising vaccine candidate for the prevention of leptospirosis.