ABSTRACT
Leptospirosis is a zoonotic disease caused by pathogenic spirochetes of theLeptospira genus. Vaccination with bacterins has severe limitations. Here, we evaluated the N-terminal region of the leptospiral immunoglobulin-like B protein (LigBrep) as a vaccine candidate against leptospirosis using immunisation strategies based on DNA prime-protein boost, DNA vaccine, and subunit vaccine. Upon challenge with a virulent strain ofLeptospira interrogans, the prime-boost and DNA vaccine approaches induced significant protection in hamsters, as well as a specific IgG antibody response and sterilising immunity. Although vaccination with recombinant fragment of LigBrep also produced a strong antibody response, it was not immunoprotective. These results highlight the potential of LigBrep as a candidate antigen for an effective vaccine against leptospirosis and emphasise the use of the DNA prime-protein boost as an important strategy for vaccine development.
Subject(s)
Animals , Cricetinae , Female , Antigens, Bacterial/immunology , Bacterial Proteins/immunology , Bacterial Vaccines/immunology , Leptospira/immunology , Leptospirosis/prevention & control , Vaccination/methods , Adjuvants, Immunologic , Biopsy , Chlorocebus aethiops , Conserved Sequence , Enzyme-Linked Immunosorbent Assay , Immunity, Humoral/immunology , Immunoglobulin A/genetics , Immunoglobulin A/immunology , Immunoglobulin G/immunology , Immunoglobulins/genetics , Immunoglobulins/immunology , Kidney/pathology , Leptospirosis/immunology , Lung/pathology , Mesocricetus , Survival Analysis , Vero Cells , Vaccines, DNA/immunology , Vaccines, Synthetic/immunology , Vaccines, Synthetic/microbiologyABSTRACT
Pathogenic Leptospira spp. are the etiological agents of leptospirosis, an important disease of both humans and animals. In urban settings, L. interrogans serovars are the predominant cause of disease in humans. The purpose of this study was to characterize a novel Leptospira isolate recovered from an abandoned swimming pool. Molecular characterization through sequencing of the rpoB gene revealed 100% identity with L. interrogans and variable-number tandem-repeat (VNTR) analysis resulted in a banding pattern identical to L. interrogans serogroup Icterohaemorrhagiae, serovar Copenhageni or Icterohaemorrhagiae. The virulence of the strain was determined in a hamster model of lethal leptospirosis. The lethal dose 50% (LD50) was calculated to be two leptospires in female hamsters and a histopathological examination of infected animals found typical lesions associated with severe leptospirosis, including renal epithelium degeneration, hepatic karyomegaly, liver-plate disarray and lymphocyte infiltration. This highly virulent strain is now available for use in further studies, especially evaluation of vaccine candidates.