Immune response and prophylactic efficacy of smegmosomes in a hamster model of leptospirosis

Leptospirosis is an important zoonotic disease worldwide. Subunit vaccines are an attractive intervention strategy against this disease, but potent, non-toxic adjuvants are necessary components to any effective vaccine. Among various adjuvant candidates, liposomes have garnered recent attention for their capacity as carriers of vaccines. In the present study we prepared novel liposomes using total polar lipids from the nonpathogenic bacterium, Mycobacterium smegmatis (designated smegmosomes). The potential for smegmosomes as a vaccine delivery/adjuvant system was evaluated with novel leptospira protective antigens (Lp0607, Lp1118, Lp1454) and compared with conventional aluminum hydroxide adjuvant (alum) in a hamster model of leptospirosis. Four-week-old hamsters were immunized subcutaneously twice at three weeks intervals and either bled at various time points to evaluate antibody responses, sacrificed to isolate splenocytes for lymphocyte proliferation and cytokine profiles in response to recall antigen, or challenged intraperitoneally with a modified lethal dose (10X MLD(50)) of virulent Leptospira interrogans serovar Pomona. Our results demonstrate that smegmosomes carrying antigens are better adjuvants than alum as revealed by enhanced and long term antibody response, lymphocyte proliferation and significant enhancement in both Th1 (IFN-gamma) and Th2 (IL-4, IL-10) cytokine production. Additionally, smegmosomes were found to induce memory responses that are significantly higher than those of alum. Above all, smegmosomes were observed to impart a significantly higher level of protection than alum as revealed by enhanced survival, reduced histopathological lesions and bacterial load in vital organs. Taken together, the data of the present study suggests that smegmosomes will serve well as a promising delivery vehicle/adjuvant system that can induce both Th1 and Th2 type immune responses and provide a novel tool in development of improved vaccines for leptospirosis and other infectious diseases.