title: A bacterial protease inhibitor protects antigens delivered in oral vaccines from digestion while triggering specific mucosal immune responses.
abstract: We report here that a bacterial protease inhibitor from Brucella spp. called U-Omp19 behaves as an ideal constituent for a vaccine formulation against infectious diseases. When co-administered orally with an antigen (Ag), U-Omp19: i) can bypass the harsh environment of the gastrointestinal tract by inhibiting stomach and intestine proteases and consequently increases the half-life of the co-administered Ag at immune inductive sites: Peyer's patches and mesenteric lymph nodes while ii) it induces the recruitment and activation of antigen presenting cells (APCs) and increases the amount of intracellular Ag inside APCs. Therefore, mucosal as well as systemic Ag-specific immune responses, antibodies, Th1, Th17 and CD8(+) T cells are enhanced when U-Omp19 is co-administered with the Ag orally. Finally, this bacterial protease inhibitor in an oral vaccine formulation confers mucosal protection and reduces parasite loads after oral challenge with virulent Toxoplasma gondii.
authors.affiliation: Instituto de Investigaciones Biotecnológicas-"Dr. Rodolfo A. Ugalde" Instituto Tecnológico de Chascomús (IIB-INTECH), Universidad Nacional de San Martín (UNSAM) CONICET, San Martín, Buenos Aires, Argentina.
authors.forename: Andrés Esteban
authors.initials: AE
authors.lastname: Ibañez
authors.affiliation: Instituto de Investigaciones Biotecnológicas-"Dr. Rodolfo A. Ugalde" Instituto Tecnológico de Chascomús (IIB-INTECH), Universidad Nacional de San Martín (UNSAM) CONICET, San Martín, Buenos Aires, Argentina.
authors.forename: Lorena Mirta
authors.initials: LM
authors.lastname: Coria
authors.affiliation: Instituto de Investigaciones Biotecnológicas-"Dr. Rodolfo A. Ugalde" Instituto Tecnológico de Chascomús (IIB-INTECH), Universidad Nacional de San Martín (UNSAM) CONICET, San Martín, Buenos Aires, Argentina.
authors.forename: Marianela Verónica
authors.initials: MV
authors.lastname: Carabajal
authors.affiliation: Instituto de Inmunología, Genética y Metabolismo (INIGEM), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad de Buenos Aires (UBA) Laboratorio de Inmunogenética, Hospital de Clínicas "José de San Martín", Facultad de Medicina, UBA, Buenos Aires, Argentina.
authors.forename: María Victoria
authors.initials: MV
authors.lastname: Delpino
authors.affiliation: Instituto de Investigaciones Biotecnológicas-"Dr. Rodolfo A. Ugalde" Instituto Tecnológico de Chascomús (IIB-INTECH), Universidad Nacional de San Martín (UNSAM) CONICET, San Martín, Buenos Aires, Argentina.
authors.forename: Gabriela Sofía
authors.initials: GS
authors.lastname: Risso
authors.affiliation: Instituto de Estudios de la Inmunidad Humoral (IDEHU), CONICET-UBA, Facultad de Farmacia y Bioquímica, UBA, Buenos Aires, Argentina; Departamento de Microbiología, Parasitología e Inmunología, Facultad de Medicina, UBA, Buenos Aires, Argentina.
authors.forename: Paula Gonzalez
authors.initials: PG
authors.lastname: Cobiello
authors.affiliation: Fundación Instituto Leloir, IIBBA-CONICET, Buenos Aires, Argentina.
authors.forename: Jimena
authors.initials: J
authors.lastname: Rinaldi
authors.affiliation: Instituto de Medicina Experimental (CONICET-Academia Nacional de Medicina), Buenos Aires, Argentina.
authors.forename: Paula
authors.initials: P
authors.lastname: Barrionuevo
authors.affiliation: Instituto de Investigaciones Biotecnológicas-"Dr. Rodolfo A. Ugalde" Instituto Tecnológico de Chascomús (IIB-INTECH), Universidad Nacional de San Martín (UNSAM) CONICET, San Martín, Buenos Aires, Argentina.
authors.forename: Laura
authors.initials: L
authors.lastname: Bruno
authors.affiliation: Instituto de Estudios de la Inmunidad Humoral (IDEHU), CONICET-UBA, Facultad de Farmacia y Bioquímica, UBA, Buenos Aires, Argentina; Departamento de Microbiología, Parasitología e Inmunología, Facultad de Medicina, UBA, Buenos Aires, Argentina.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Frank
authors.affiliation: Fundación Instituto Leloir, IIBBA-CONICET, Buenos Aires, Argentina.
authors.forename: Sebastián
authors.initials: S
authors.lastname: Klinke
authors.affiliation: Fundación Instituto Leloir, IIBBA-CONICET, Buenos Aires, Argentina.
authors.forename: Fernando Alberto
authors.initials: FA
authors.lastname: Goldbaum
authors.affiliation: Instituto de Investigaciones Biotecnológicas-"Dr. Rodolfo A. Ugalde" Instituto Tecnológico de Chascomús (IIB-INTECH), Universidad Nacional de San Martín (UNSAM) CONICET, San Martín, Buenos Aires, Argentina.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Briones
authors.affiliation: Instituto de Inmunología, Genética y Metabolismo (INIGEM), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad de Buenos Aires (UBA) Laboratorio de Inmunogenética, Hospital de Clínicas "José de San Martín", Facultad de Medicina, UBA, Buenos Aires, Argentina.
authors.forename: Guillermo Hernán
authors.initials: GH
authors.lastname: Giambartolomei
authors.affiliation: Instituto de Investigaciones Biotecnológicas-"Dr. Rodolfo A. Ugalde" Instituto Tecnológico de Chascomús (IIB-INTECH), Universidad Nacional de San Martín (UNSAM) CONICET, San Martín, Buenos Aires, Argentina.
authors.forename: Karina Alejandra
authors.initials: KA
authors.lastname: Pasquevich
authors.affiliation: Instituto de Investigaciones Biotecnológicas-"Dr. Rodolfo A. Ugalde" Instituto Tecnológico de Chascomús (IIB-INTECH), Universidad Nacional de San Martín (UNSAM) CONICET, San Martín, Buenos Aires, Argentina. Electronic address: jucassataro@iibintech.com.ar.
authors.forename: Juliana
authors.initials: J
authors.lastname: Cassataro
mesh_terms: D000284:Administration, Oral; D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000378:metabolism*; D001426:Bacterial Proteins / Q000494:pharmacology*; D002002:Brucella / Q000737:chemistry*; D005260:Female; D018928:Immunity, Mucosal; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D011480:Protease Inhibitors / Q000494:pharmacology*; D014612:Vaccines / Q000276:immunology*
chemical_list: D000941:Antigens; D001426:Bacterial Proteins; D011480:Protease Inhibitors; D014612:Vaccines
keywords: Adjuvant; Antigen delivery; Brucella spp.; Oral vaccination; Protease inhibitor