Leptospirosis is a disease caused by pathogenic spirochetes of the Leptospira
). Transmission occurs through direct or indirect exposure to urine of mammalian reservoirs, especially during floods, occupational exposure, and the practice of water sports (3
). The infection usually manifests as asymptomatic or as a self-resolving febrile illness. However, up to 15% of all human infections progress to severe leptospirosis, with complications such as kidney failure and pulmonary hemorrhage and fatality rates of up to 50% (11
). Mortality remains high because of delays in diagnosis due to lack of infrastructure and adequate clinical suspicion and to other poorly understood reasons, especially in underdeveloped and developing countries (3
Although vaccination is the recommended method of prevention in at-risk settings (17
), the immune response generated by most of the currently available vaccines (bacterins) is attributable to the outer membrane lipopolysaccharide (LPS) component (29
). As over 250 leptospiral serovars have been identified thus far (7
), with the main antigenic differences attributed to the LPS, the efficacy of such vaccines has been found to be limited to short-term, serovar-specific immunity. Bacterin-type vaccines have been approved for use in humans in Cuba, China, Japan, and France. However, bacterins induce adverse reactions and side effects and, in general, their use has been restricted to animals (21
), especially dogs, cattle, and pigs (1
). Therefore, considerable effort is being made to identify novel leptospiral vaccine candidates with fewer side effects that can induce a cross-protective immune response to the pathogenic serovars.
In recent years, many potential vaccine candidates have been tested in animal models, and several different approaches, including those employing subunit, DNA, adenovirus, and Mycobacterium bovis
BCG constructs, have been used (2
). Most of these studies identified their protein targets by screening for antigenicity through the use of sera from patients with leptospirosis (14
) and/or proteins with predicted surface exposure (10
). However, a recent review highlighted the difficulties of evaluating the reports of efficacy for these vaccine candidates due to the different animal models and statistical methods used. The authors of the review reported that when the same method of statistical analysis of protection against mortality was used, very few candidates were found to offer significant immunoprotection (1
). In the majority of reports, furthermore, protection did not induce sterilizing immunity.
Recently, our group used an approach based on reverse vaccinology to identify eight putative lipoproteins in the L. interrogans
genome and to subsequently characterize those lipoproteins in terms of immunogenicity and antigenicity (16
). The eight putative lipoproteins and an additional 19 proteins, predicted to be surface exposed and recognized by sera from convalescent patients with leptospirosis (14
), were evaluated using a hamster model of lethal leptospirosis. The aim of the study was to identify potential vaccine candidates that could protect hamsters against lethal challenge; the endpoints used in the present study included survival and protection against mortality.