A Live Diarrheal Vaccine Imprints a Th2 Cell Bias and Acts as an Anti-Inflammatory Vaccine

• Published in: Journal of Immunology Vol. 175; no. 10; pp. 6733 - 6740
• Main Authors: Jun, SangMu, Gilmore, Wendy, Callis, Gayle, Rynda, Agnieszka, Haddad, Asmahan, Pascual, David W
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15-11-2005
• Subjects: Administration, Oral; Animals; Antigens, Bacterial - genetics; Bacterial Vaccines - administration & dosage; Bacterial Vaccines - genetics; Bacterial Vaccines - immunology; Bacterial Vaccines - pharmacology; Cytokines - biosynthesis; Diarrhea - immunology; Diarrhea - microbiology; Diarrhea - prevention & control; Encephalomyelitis, Autoimmune, Experimental - immunology; Encephalomyelitis, Autoimmune, Experimental - pathology; Encephalomyelitis, Autoimmune, Experimental - prevention & control; Escherichia coli; Escherichia coli - immunology; Escherichia coli Infections - immunology; Escherichia coli Infections - microbiology; Escherichia coli Infections - prevention & control; Female; Fimbriae Proteins - genetics; Genetic Vectors; Mice; Myelin Proteolipid Protein - immunology; Peptide Fragments - immunology; Salmonella; Salmonella - genetics; Th2 Cells - immunology
• ISSN: 0022-1767; 1550-6606; 1365-2567
• DOI: 10.4049/jimmunol.175.10.6733

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.