title: Mechanisms Underlying the Immune Response Generated by an Oral Vibrio cholerae Vaccine.
abstract: Mechanistic details underlying the resulting protective immune response generated by mucosal vaccines remain largely unknown. We investigated the involvement of Toll-like receptor signaling in the induction of humoral immune responses following oral immunization with Dukoral, comparing wild type mice with TLR-2-, TLR-4-, MyD88- and Trif-deficient mice. Although all groups generated similar levels of IgG antibodies, the proliferation of CD4+ T-cells in response to V. cholerae was shown to be mediated via MyD88/TLR signaling, and independently of Trif signaling. The results demonstrate differential requirements for generation of immune responses. These results also suggest that TLR pathways may be modulators of the quality of immune response elicited by the Dukoral vaccine. Determining the critical signaling pathways involved in the induction of immune response to this vaccine would be beneficial, and could contribute to more precisely-designed versions of other oral vaccines in the future.
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada. dsirskyj@gmail.com.|Children's Hospital of Eastern Ontario (CHEO)-Research Institute, Ottawa, ON K1H 5B2, Canada. dsirskyj@gmail.com.
authors.forename: Danylo
authors.initials: D
authors.lastname: Sirskyj
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada. akumar@uottawa.ca.|Children's Hospital of Eastern Ontario (CHEO)-Research Institute, Ottawa, ON K1H 5B2, Canada. akumar@uottawa.ca.|Department of Pathology and Laboratory Medicine, University of Ottawa, 451 Smyth Rd, Ottawa, ON K1H 8M5, Canada. akumar@uottawa.ca.
authors.forename: Ashok
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Ottawa, 451 Smyth Rd, Ottawa, ON K1H 8M5, Canada. aazizi@uottawa.ca.
authors.forename: Ali
authors.initials: A
authors.lastname: Azizi
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000276:immunology; D000284:Administration, Oral; D000818:Animals; D002771:Cholera / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D022121:Cholera Vaccines / Q000493:pharmacokinetics*; D051379:Mice; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology*; D014734:Vibrio cholerae
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D022121:Cholera Vaccines; D053594:Myeloid Differentiation Factor 88; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; C507780:Myd88 protein, mouse; C476286:Ticam1 protein, mouse; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse
keywords: Toll-like receptor; Vibrio cholerae; humoral immunity; oral vaccine