title: Salmonella Typhi OmpS1 and OmpS2 porins are potent protective immunogens with adjuvant properties.
abstract: Salmonella enterica serovar Typhi (S. Typhi) is the causal agent of typhoid fever, a disease that primarily affects developing countries. Various antigens from this bacterium have been reported to be targets of the immune response. Recently, the S. Typhi genome has been shown to encode two porins--OmpS1 and OmpS2--which are expressed at low levels under in vitro culture conditions. In this study, we demonstrate that immunizing mice with either OmpS1 or OmpS2 induced production of specific, long-term antibody titres and conferred protection against S. Typhi challenge; in particular, OmpS1 was more immunogenic and conferred greater protective effects than OmpS2. We also found that OmpS1 is a Toll-like receptor 4 (TLR4) agonist, whereas OmpS2 is a TLR2 and TLR4 agonist. Both porins induced the production of tumour necrosis factor and interleukin-6, and OmpS2 was also able to induce interleukin-10 production. Furthermore, OmpS1 induced the over-expression of MHC II molecules in dendritic cells and OmpS2 induced the over-expression of CD40 molecules in macrophages and dendritic cells. Co-immunization of OmpS1 or OmpS2 with ovalbumin (OVA) increased anti-OVA antibody titres, the duration and isotype diversity of the OVA-specific antibody response, and the proliferation of T lymphocytes. These porins also had adjuvant effects on the antibody response when co-immunized with either the Vi capsular antigen from S. Typhi or inactivated 2009 pandemic influenza A(H1N1) virus [A(H1N1)pdm09]. Taken together, the data indicate that OmpS1 and OmpS2, despite being expressed at low levels under in vitro culture conditions, are potent protective immunogens with intrinsic adjuvant properties.
authors: Medical Research Unit on Immunochemistry, National Medical Centre Siglo XXI, Mexican Social Security Institute (IMSS), Specialties Hospital, Mexico City, Mexico.
authors: Mario A
authors: MA
authors: Moreno-Eutimio
authors: Alejandra
authors: A
authors: Tenorio-Calvo
authors: Rodolfo
authors: R
authors: Pastelin-Palacios
authors: Christian
authors: C
authors: Perez-Shibayama
authors: Cristina
authors: C
authors: Gil-Cruz
authors: Rubén
authors: R
authors: López-Santiago
authors: Isabel
authors: I
authors: Baeza
authors: Marcos
authors: M
authors: Fernández-Mora
authors: Laura
authors: L
authors: Bonifaz
authors: Armando
authors: A
authors: Isibasi
authors: Edmundo
authors: E
authors: Calva
authors: Constantino
authors: C
authors: López-Macías
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000235:genetics; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood*; D001425:Bacterial Outer Membrane Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D005260:Female; D057809:HEK293 Cells; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D007114:Immunization; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000276:immunology; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D011135:Polysaccharides, Bacterial / Q000276:immunology; D018272:Porins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D022562:Salmonella Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D012485:Salmonella typhi / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000819:agonists / Q000378:metabolism; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014435:Typhoid Fever / Q000097:blood / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D000949:Histocompatibility Antigens Class II; C556062:IL10 protein, mouse; D007252:Influenza Vaccines; D015850:Interleukin-6; C094202:OmpS1 protein, Salmonella typhi; C583286:OmpS2 protein, Salmonella typhi; D011135:Polysaccharides, Bacterial; D018272:Porins; D022562:Salmonella Vaccines; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C054154:capsular polysaccharide, Salmonella; D016753:Interleukin-10; D010047:Ovalbumin
keywords: OmpS1; OmpS2; Salmonella; adjuvants; porins; vaccines