Neglected tropical diseases, including zoonoses such as leptospirosis, have a major impact on rural and poor urban communities, particularly in developing countries. This has led to major investment in antipoverty vaccines that focus on diseases that influence public health and thereby productivity. While the true, global, impact of leptospirosis is unknown due to the lack of adequate laboratory diagnosis, the WHO estimates that incidence has doubled over the last 15 years to over 1 million cases that require hospitalization every year. Leptospirosis is caused by pathogenic Leptospira spp. and is spread through direct contact with infected animals, their urine or contaminated water and soil. Inactivated leptospirosis vaccines, or bacterins, are approved in only a handful of countries due to the lack of heterologous protection (there are > 250 pathogenic Leptospira serovars) and the serious side-effects associated with vaccination. Currently, research has focused on recombinant vaccines, a possible solution to these problems. However, due to a lack of standardised animal models, rigorous statistical analysis and poor reproducibility, this approach has met with limited success. We evaluated a subunit vaccine preparation, based on a conserved region of the leptospiral immunoglobulin-like B protein (LigB(131–645)) and aluminium hydroxide (AH), in the hamster model of leptospirosis. The vaccine conferred significant protection (80.0–100%, P < 0.05) against mortality in vaccinated animals in seven independent experiments. The efficacy of the LigB(131–645)/AH vaccine ranged from 87.5–100% and we observed sterile immunity (87.5–100%) among the vaccinated survivors. Significant levels of IgM and IgG were induced among vaccinated animals, although they did not correlate with immunity. A mixed IgG1/IgG2 subclass profile was associated with the subunit vaccine, compared to the predominant IgG2 profile seen in bacterin vaccinated hamsters. These findings suggest that LigB(131–645) is a vaccine candidate against leptospirosis with potential ramifications to public and veterinary health.

The mouse disease model has the advantage of a broad array of immunological and genetic tools available for basic research. Some studies on transgenic and/or mutant mouse strains as models for experimental leptospirosis have been reported; however, the wider use of such models is hampered by a poor understanding of the outcome of experimental leptospiral infection among the different mouse strains available. Here, the outcome of infection by a virulent strain of Leptospira interrogans serogroup Icterohaemorrhagiae strain Cop was studied in four commonly used wildtype mouse strains: A, CBA, BALB/c and C57BL/6. The end points evaluated in this study were survival, presence of kidney lesions, leptospiral load in kidney samples, microscopic agglutination test titre and anti-leptospiral IgG antibody levels. As expected, none of the mouse strains were susceptible to lethal leptospirosis. However, these strains developed specific pathologies associated with sublethal leptospirosis. The A and C57BL/6 strains exhibited a high leptospiral load in kidney samples and the CBA and C57BL/6 strains developed severe inflammatory lesions, whilst the BALB/c strain proved to be the most resistant to subclinical leptospirosis.

The aims of this study were to investigate the frequency of pulmonary hemorrhage (PH) in mice unable to produce functional B and T lymphocytes and to explore the effect of an inducible nitric oxide synthase gene (Inos) knockout (KO) on the frequency/severity of interstitial nephritis in vivo. We studied the outcome of infection by the virulent Leptospira interrogans serovar Copenhageni strain Cop. The animals used were Inos KO mice, recombination activating gene 1 (Rag1) KO mice, CB17 severe combined immunodeficiency (SCID) mice, and the respective wild-type (WT) C57BL/6 and BALB/c controls. The Inos KO and WT mice survived with no clinical symptoms of leptospirosis. The frequency and severity of nephritis was significantly lower in the Inos KO mice. All of the Rag1 KO and SCID animals died of acute leptospirosis, whereas all of the WT mice survived. PH was observed in 57 and 94% of Rag1 KO mice and in 83 and 100% of SCID mice, using inoculum doses of 10 7 and 10 6 leptospires, respectively. There was no evidence of PH in the WT controls. In conclusion, the loss of the Inos gene had a negligible effect on the outcome of leptospiral infection, although we observed a reduced susceptibility for interstitial nephritis in this group. Of note, the absence of functional B-and T-cell lymphocytes did not preclude the occurrence of PH. These data provide evidence that PH in leptospirosis may not be related only to autoimmune mechanisms.

Only recently, knockout mouse models were applied in studies on the pathogenesis of leptospirosis. Current data suggest an important role of innate immunity receptors and interferon gamma dependant cellular response on protection. It is not clear, however, whether T helper cell polarization influences on outcome of leptospiral infection. We report findings of experimental infection of C57BL/6 (interferon gamma or tumor necrosis factor alpha receptor deficient) and BALB/c (interleukin 4 deficient) mice infected by pathogenic Leptospira interrogans serovar Copenhageni. Specific cytokine gene deficiency had no impact on outcome since all animals survived. TNFR knockout mice, however, exhibited more severe residual renal inflammation during convalescence thus suggesting this cytokine is important in early control of infection, protecting kidneys from relevant pathology.