Recombinant chimeric proteins offer new hope to control of leptospirosis.

Leptospirosis is an emerging zoonotic disease that causes over a million human cases and numerous fatalities annually, imposing substantial public health, economic, and veterinary burdens worldwide. Despite its impact, control strategies remain limited, as commercial bacterin vaccines offer only short-term, serovar-specific protection. The extensive genetic and antigenic diversity of Leptospira species presents a major challenge to the development of broadly protective vaccines. In response, several alternative strategies have been explored, including DNA vaccines, viral-vectored platforms and multi-epitope recombinant chimeric proteins. Among these, chimeric constructs have emerged as promising candidates due to their ability to combine conserved immunogenic regions from multiple antigens, potentially eliciting broader and more effective immune responses. Advances in immunoinformatics, reverse vaccinology and structural modeling have enabled the rational design of these constructs, allowing for the identification of B- and T-cell epitopes with high antigenic potential and wide population coverage. This mini-review provides an overview of recent progress in the development of innovative vaccine strategies against leptospirosis, with particular focus on recombinant chimeric proteins. We discuss the advantages and limitations, highlighting their potential to enhance cross-protection and contribute to more effective control of leptospirosis.