From Classical Bacterins to Recombinant Vaccines: Critical Aspects of the Immune Response in Ruminants.

Leptospirosis is a neglected zoonosis causing significant economic losses in livestock, primarily through Bovine Genital Leptospirosis (BGL). While current vaccines prevent clinical disease, they typically fail to provide sterilizing immunity against adapted strains. This allows Leptospira to persist in the genitourinary tract, maintaining environmental shedding and zoonotic risk. Achieving sterilizing immunity remains a challenge, and this gap may be closely related to the immune response pattern of ruminants, where effective protection against chronic colonization requires, besides the humoral response, a robust cellular immune response (Th1/IgG2). Recent studies indicate that adjuvants based on oil emulsions or biodegradable polymers are better at inducing Th1/IgG2 responses and the proliferation of CD4+ T cells, as well as WC1+ γδ T cells, which may be essential for eliminating Leptospira from renal and probably also genital tissues. Thus, overcoming chronic colonization through inducing the Th1-type immune response may be the main challenge for vaccination to fulfill its role in sustaining herd immunity and mitigation of zoonotic risk, in line with the One Health approach. In this context, we aimed to critically examine immune mechanisms in ruminants, advances in vaccine platforms and adjuvant strategies against bovine leptospirosis and outline the challenges that must be overcome to achieve sterilizing immunity.