title: Split immune response after oral vaccination of mice with recombinant Escherichia coli Nissle 1917 expressing fimbrial adhesin K88.
abstract: Enterotoxigenic Escherichia coli (ETEC) are a leading cause of diarrhoea in piglets and newborn calves. Massive efforts have therefore been made to develop a vaccine for the induction of protective mucosal immunity against ETEC. Since it has been shown that the probiotic strain E. coli Nissle 1917 (EcN) can serve as a safe carrier for targeted delivery of recombinant molecules to the intestinal mucosa, we constructed the recombinant strain EcN pMut2-kanK88 (EcN-K88) stably expressing the determinant for the K88 fimbrial adhesin of ETEC on the bacterial surface. After oral application of EcN-K88 to mice for one week, EcN-K88 as well as wild-type EcN and EcN mock-transformed with the plasmid vector only could be detected in faecal samples for a minimum of 7 days after the last feeding, indicating that EcN can transiently colonise the murine intestine. Oral application of EcN-K88 resulted in significant IgG serum titres against K88 as early as 7 days after the initial feeding with EcN-K88, but no significant IgA titres. In contrast, we failed to detect any specific T cell responses towards the K88 antigen both in spleen and mesenteric lymph nodes. Although dendritic cells readily upregulated maturation and activation markers in response to K88 stimulation, accompanied by secretion of interleukin (IL)-12, IL-6, IL-10, and tumour necrosis factor, restimulation of T cells from mice having received EcN-K88 with K88-loaded dendritic cells did not result in detectable T cell proliferation and IL-2 secretion, but rather induced an IL-10 bias. While the serum antibody responses clearly demonstrate that K88 is recognized by the humoral immune system, our findings indicate that oral application of probiotic EcN expressing the K88 fimbrial adhesin does not induce a selective T cell response towards the antigen.
authors.affiliation: University of Würzburg, Institute for Molecular Infection Biology, Würzburg, Germany.
authors.forename: Katharina A
authors.initials: KA
authors.lastname: Remer
authors.forename: Marita
authors.initials: M
authors.lastname: Bartrow
authors.forename: Bianca
authors.initials: B
authors.lastname: Roeger
authors.forename: Heidrun
authors.initials: H
authors.lastname: Moll
authors.forename: Ulrich
authors.initials: U
authors.lastname: Sonnenborn
authors.forename: Tobias A
authors.initials: TA
authors.lastname: Oelschlaeger
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000096:biosynthesis* / Q000276:immunology*; D015169:Colony Count, Microbial; D016207:Cytokines / Q000378:metabolism; D004926:Escherichia coli / Q000276:immunology*; D029968:Escherichia coli Proteins / Q000096:biosynthesis* / Q000276:immunology*; D022361:Escherichia coli Vaccines / Q000008:administration & dosage / Q000276:immunology*; D005243:Feces / Q000382:microbiology; D005260:Female; D036781:Fimbriae Proteins / Q000096:biosynthesis* / Q000276:immunology*; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D016207:Cytokines; D029968:Escherichia coli Proteins; D022361:Escherichia coli Vaccines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; C026888:K88 antigen, E coli; D014614:Vaccines, Synthetic; D036781:Fimbriae Proteins