title: A live diarrheal vaccine imprints a Th2 cell bias and acts as an anti-inflammatory vaccine.
abstract: An experimental vaccine for enterotoxigenic Escherichia coli (ETEC) composed of a live, attenuated Salmonella vector-expressing enterotoxigenic E. coli fimbriae, colonization factor Ag I (CFA/I), stimulated a biphasic Th cell response when given orally and suppressed the normally produced proinflammatory response. Such suppression was also evident upon the Salmonella-CFA/I infection of macrophages resulting in diminished TNF-alpha, IL-1, and IL-6 production and suggesting that the CFA/I fimbrial expression by Salmonella may protect against a proinflammatory disease. To test this hypothesis, SJL/J mice were vaccinated with Salmonella-CFA/I construct 1 or 4 wk before induction of experimental autoimmune encephalomyelitis using an encephalitogenic proteolipid protein peptide, PLP(139-151). Mice receiving Salmonella-CFA/I vaccine recovered completely from mild acute clinical disease and showed only mild inflammatory infiltrates in the spinal cord white and gray matter. This protective effect was accompanied by a loss of encephalitogenic IFN-gamma-secreting Th cells and was replaced with an increase in IL-4, IL-10, and IL-13 secretion. Collectively, these data suggested that Salmonella-CFA/I is an anti-inflammatory vaccine that down-regulates proinflammatory cells and confers protection against a proinflammatory disease, experimental autoimmune encephalomyelitis, via immune deviation.
authors.affiliation: Veterinary Molecular Biology, Montana State University, Bozeman, MT 59717-3610, USA.
authors.forename: SangMu
authors.initials: S
authors.lastname: Jun
authors.forename: Wendy
authors.initials: W
authors.lastname: Gilmore
authors.forename: Gayle
authors.initials: G
authors.lastname: Callis
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Rynda
authors.forename: Asmahan
authors.initials: A
authors.lastname: Haddad
authors.forename: David W
authors.initials: DW
authors.lastname: Pascual
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis; D003967:Diarrhea / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D004926:Escherichia coli / Q000276:immunology*; D004927:Escherichia coli Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D005260:Female; D036781:Fimbriae Proteins / Q000235:genetics; D005822:Genetic Vectors; D051379:Mice; D018991:Myelin Proteolipid Protein / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D012475:Salmonella / Q000235:genetics; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D016207:Cytokines; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; C022924:colonization factor antigens; C435023:myelin proteolipid protein (139-151); D036781:Fimbriae Proteins