title: Immunization with recombinant Brucella species outer membrane protein Omp16 or Omp19 in adjuvant induces specific CD4+ and CD8+ T cells as well as systemic and oral protection against Brucella abortus infection.
abstract: Available vaccines against Brucella spp. are live attenuated Brucella strains. In order to engineer a better vaccine to be used in animals and humans, our laboratory aims to develop an innocuous subunit vaccine. Particularly, we are interested in the outer membrane proteins (OMPs) of B. abortus: Omp16 and Omp19. In this study, we assessed the use of these proteins as vaccines against Brucella in BALB/c mice. Immunization with lipidated Omp16 (L-Omp16) or L-Omp19 in incomplete Freund's adjuvant (IFA) conferred significant protection against B. abortus infection. Vaccination with unlipidated Omp16 (U-Omp16) or U-Omp19 in IFA induced a higher degree of protection than the respective lipidated versions. Moreover, the level of protection induced after U-Omp16 or U-Omp19 immunization in IFA was similar to that elicited by live B. abortus S19 immunization. Flow cytometric analysis showed that immunization with U-Omp16 or U-Omp19 induced antigen-specific CD4(+) as well as CD8(+) T cells producing gamma interferon. In vivo depletion of CD4(+) or CD8(+) T cells in mice immunized with U-Omp16 or U-Omp19 plus IFA resulted in a loss of the elicited protection, indicating that both cell types are mediating immune protection. U-Omp16 or U-Omp19 vaccination induced a T helper 1 response, systemic protection in aluminum hydroxide formulation, and oral protection with cholera toxin adjuvant against B. abortus infection. Both immunization routes exhibited a similar degree of protection to attenuated Brucella vaccines (S19 and RB51, respectively). Overall these results indicate that U-Omp16 or U-Omp19 would be a useful candidate for a subunit vaccine against human and animal brucellosis.
authors.affiliation: Laboratorio de Inmunogenética, Hospital de Clínicas José de San Martín, Facultad de Medicina, Universidad de Buenos Aires, Córdoba 2351 3 Piso Sala 4 (1120), Buenos Aires, Argentina.
authors.forename: Karina A
authors.initials: KA
authors.lastname: Pasquevich
authors.forename: Silvia M
authors.initials: SM
authors.lastname: Estein
authors.forename: Clara
authors.initials: C
authors.lastname: García Samartino
authors.forename: Clara García
authors.initials: CG
authors.lastname: Samartino
authors.forename: Astrid
authors.initials: A
authors.lastname: Zwerdling
authors.forename: Lorena M
authors.initials: LM
authors.lastname: Coria
authors.forename: Paula
authors.initials: P
authors.lastname: Barrionuevo
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Fossati
authors.forename: Guillermo H
authors.initials: GH
authors.lastname: Giambartolomei
authors.forename: Juliana
authors.initials: J
authors.lastname: Cassataro
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000494:pharmacology; D000536:Aluminum Hydroxide / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001425:Bacterial Outer Membrane Proteins / Q000008:administration & dosage / Q000276:immunology*; D002004:Brucella Vaccine / Q000276:immunology*; D002003:Brucella abortus / Q000276:immunology*; D002006:Brucellosis / Q000517:prevention & control*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002772:Cholera Toxin / Q000008:administration & dosage / Q000494:pharmacology; D015169:Colony Count, Microbial; D005260:Female; D005434:Flow Cytometry; D005620:Freund's Adjuvant / Q000008:administration & dosage* / Q000494:pharmacology; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis; D047589:Leukocyte Reduction Procedures; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000382:microbiology; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002004:Brucella Vaccine; D007074:Immunoglobulin G; D022223:Vaccines, Subunit; D000536:Aluminum Hydroxide; D007371:Interferon-gamma; D005620:Freund's Adjuvant; D002772:Cholera Toxin