title: Protective Immunity and Reduced Renal Colonization Induced by Vaccines Containing Recombinant Leptospira interrogans Outer Membrane Proteins and Flagellin Adjuvant.
abstract: Leptospirosis is a global zoonotic disease caused by different Leptospira species, such as Leptospira interrogans, that colonize the renal tubules of wild and domestic animals. Thus far, attempts to develop effective leptospirosis vaccines, both for humans and animals, have failed to induce immune responses capable of conferring protection and simultaneously preventing renal colonization. In this study, we evaluated the protective immunity induced by subunit vaccines containing seven different recombinant Leptospira interrogans outer membrane proteins, including the carboxy-terminal portion of the immunoglobulinlike protein A (LigA(C)) and six novel antigens, combined with aluminum hydroxide (alum) or Salmonella flagellin (FliC) as adjuvants. Hamsters vaccinated with the different formulations elicited high antigen-specific antibody titers. Immunization with LigA(C), either with alum or flagellin, conferred protective immunity but did not prevent renal colonization. Similarly, animals immunized with LigA(C) or LigA(C) coadministered with six leptospiral proteins with alum adjuvant conferred protection but did not reduce renal colonization. In contrast, immunizing animals with the pool of seven antigens in combination with flagellin conferred protection and significantly reduced renal colonization by the pathogen. The present study emphasizes the relevance of antigen composition and added adjuvant in the efficacy of antileptospirosis subunit vaccines and shows the complex relationship between immune responses and renal colonization by the pathogen.
authors.affiliation: Laboratório de Bacteriologia, Instituto Butantan, São Paulo, SP, Brazil Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: D
authors.initials: D
authors.lastname: Monaris
authors.affiliation: Centro de Biotecnologia, Instituto Butantan, São Paulo, SP, Brazil.
authors.forename: M E
authors.initials: ME
authors.lastname: Sbrogio-Almeida
authors.affiliation: Laboratório de Tuberculose, Instituto Biológico, São Paulo, SP Brazil.
authors.forename: C C
authors.initials: CC
authors.lastname: Dib
authors.affiliation: Laboratório de Imunogenética, Instituto Butantan, São Paulo, SP, Brazil.
authors.forename: T A
authors.initials: TA
authors.lastname: Canhamero
authors.affiliation: Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: G O
authors.initials: GO
authors.lastname: Souza
authors.affiliation: Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: S A
authors.initials: SA
authors.lastname: Vasconcellos
authors.affiliation: Laboratório de Desenvolvimento de Vacinas, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: L C S
authors.initials: LC
authors.lastname: Ferreira
authors.affiliation: Laboratório de Bacteriologia, Instituto Butantan, São Paulo, SP, Brazil patricia.aniz@butantan.gov.br.
authors.forename: P A E
authors.initials: PA
authors.lastname: Abreu
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000536:Aluminum Hydroxide / Q000008:administration & dosage; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D005408:Flagellin / Q000008:administration & dosage*; D007074:Immunoglobulin G / Q000097:blood; D007668:Kidney / Q000382:microbiology; D007921:Leptospira interrogans / Q000235:genetics / Q000276:immunology*; D007922:Leptospirosis / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D008647:Mesocricetus; D016019:Survival Analysis; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D007074:Immunoglobulin G; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; D005408:Flagellin; D000536:Aluminum Hydroxide