title: Vaccination with a single CD4 T cell peptide epitope from a Salmonella type III-secreted effector protein provides protection against lethal infection.
abstract: Salmonella infections affect millions worldwide and remain a significant cause of morbidity and mortality. It is known from mouse studies that CD4 T cells are essential mediators of immunity against Salmonella infection, yet it is not clear whether targeting CD4 T cell responses directly with peptide vaccines against Salmonella can be effective in combating infection. Additionally, it is not known whether T cell responses elicited against Salmonella secreted effector proteins can provide protective immunity against infection. In this study, we investigated both of these possibilities using prime-boost immunization of susceptible mice with a single CD4 T cell peptide epitope from Salmonella secreted effector protein I (SseI), a component of the Salmonella type III secretion system. This immunization conferred significant protection against lethal oral infection, equivalent to that conferred by whole heat-killed Salmonella bacteria. Surprisingly, a well-characterized T cell epitope from the flagellar protein FliC afforded no protection compared to immunization with an irrelevant control peptide. The protective response appeared to be most associated with polyfunctional CD4 T cells raised against the SseI peptide, since no antibodies were produced against any of the peptides and very little CD8 T cell response was observed. Overall, this study demonstrates that eliciting CD4 T cell responses against components of the Salmonella type III secretion system can contribute to protection against infection and should be considered in the design of future Salmonella subunit vaccines.
authors.affiliation: Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, Louisiana, USA.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Kurtz
authors.forename: Hailey E
authors.initials: HE
authors.lastname: Petersen
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Frederick
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Morici
authors.forename: James B
authors.initials: JB
authors.lastname: McLachlan
mesh_terms: D000818:Animals; D058947:Bacterial Secretion Systems / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D012480:Salmonella Infections / Q000517:prevention & control*; D012486:Salmonella typhimurium / Q000276:immunology*; D014611:Vaccination / Q000379:methods*
chemical_list: D058947:Bacterial Secretion Systems; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte