title: The protein moiety of Brucella abortus outer membrane protein 16 is a new bacterial pathogen-associated molecular pattern that activates dendritic cells in vivo, induces a Th1 immune response, and is a promising self-adjuvanting vaccine against systemic and oral acquired brucellosis.
abstract: Knowing the inherent stimulatory properties of the lipid moiety of bacterial lipoproteins, we first hypothesized that Brucella abortus outer membrane protein (Omp)16 lipoprotein would be able to elicit a protective immune response without the need of external adjuvants. In this study, we demonstrate that Omp16 administered by the i.p. route confers significant protection against B. abortus infection and that the protective response evoked is independent of the protein lipidation. To date, Omp16 is the first Brucella protein that without the requirement of external adjuvants is able to induce similar protection levels to the control live vaccine S19. Moreover, the protein portion of Omp16 (unlipidated Omp16 [U-Omp16]) elicits a protective response when administered by the oral route. Either systemic or oral immunization with U-Omp16 elicits a Th1-specific response. These abilities of U-Omp16 indicate that it is endowed with self-adjuvanting properties. The adjuvanticity of U-Omp16 could be explained, at least in part, by its capacity to activate dendritic cells in vivo. U-Omp16 is also able to stimulate dendritic cells and macrophages in vitro. The latter property and its ability to induce a protective Th1 immune response against B. abortus infection have been found to be TLR4 dependent. The facts that U-Omp16 is an oral protective Ag and possesses a mucosal self-adjuvanting property led us to develop a plant-made vaccine expressing U-Omp16. Our results indicate that plant-expressed recombinant U-Omp16 is able to confer protective immunity, when given orally, indicating that a plant-based oral vaccine expressing U-Omp16 could be a valuable approach to controlling this disease.
authors.affiliation: Laboratory of Immunogenetics, Clinical Hospital José de San Martín, School of Medicine, University of Buenos Aires, Buenos Aires.
authors.forename: Karina A
authors.initials: KA
authors.lastname: Pasquevich
authors.forename: Clara
authors.initials: C
authors.lastname: García Samartino
authors.forename: Lorena M
authors.initials: LM
authors.lastname: Coria
authors.forename: Silvia M
authors.initials: SM
authors.lastname: Estein
authors.forename: Astrid
authors.initials: A
authors.lastname: Zwerdling
authors.forename: Andrés E
authors.initials: AE
authors.lastname: Ibañez
authors.forename: Paula
authors.initials: P
authors.lastname: Barrionuevo
authors.forename: Fernanda Souza de
authors.initials: FS
authors.lastname: Oliveira
authors.forename: Natalia Barbosa
authors.initials: NB
authors.lastname: Carvalho
authors.forename: Julia
authors.initials: J
authors.lastname: Borkowski
authors.forename: Sergio Costa
authors.initials: SC
authors.lastname: Oliveira
authors.forename: Heribert
authors.initials: H
authors.lastname: Warzecha
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 / Q000235:genetics; D000284:Administration, Oral; D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D002004:Brucella Vaccine / Q000008:administration & dosage / Q000276:immunology*; D002006:Brucellosis / Q000276:immunology / Q000517:prevention & control*; D002454:Cell Differentiation / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005620:Freund's Adjuvant / Q000008:administration & dosage; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology*; D007111:Immunity, Cellular; D007274:Injections, Intraperitoneal; D008055:Lipids / Q000008:administration & dosage; D008074:Lipoproteins / Q000008:administration & dosage / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018417:Th1 Cells / Q000276:immunology* / Q000382:microbiology; D014026:Nicotiana / Q000235:genetics / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002004:Brucella Vaccine; D008055:Lipids; D008074:Lipoproteins; C114843:incomplete Freund's adjuvant; D005620:Freund's Adjuvant