TY - JOUR
T1 - Dual immunization with sseb/flagellin provides enhanced protection against salmonella infection mediated by circulating memory cells
AU - Lee, Seung Joo
AU - Benoun, Joseph
AU - Sheridan, Brian S.
AU - Fogassy, Zachary
AU - Pham, Oanh
AU - Pham, Quynh Mai
AU - Puddington, Lynn
AU - Mcsorley, Stephen J
PY - 2017/8/15
Y1 - 2017/8/15
N2 - The development of a subunit Salmonella vaccine has been hindered by the absence of detailed information about antigenic targets of protective Salmonella-specific T and B cells. Recent studies have identified SseB as a modestly protective Ag in susceptible C57BL/6 mice, but the mechanism of protective immunity remains undefined. In this article, we report that simply combining Salmonella SseB with flagellin substantially enhances protective immunity, allowing immunized C57BL/6 mice to survive for up to 30 d following challenge with virulent bacteria. Surprisingly, the enhancing effect of flagellin did not require flagellin Ag targeting during secondary responses or recognition of flagellin by TLR5. Although coimmunization with flagellin did not affect SseB-specific Ab responses, it modestly boosted CD4 responses. In addition, protective immunity was effectively transferred in circulation to parabionts of immunized mice, demonstrating that tissue-resident memory is not required for vaccine-induced protection. Finally, protective immunity required host expression of IFN-γR but was independent of induced NO synthase expression. Taken together, these data indicate that Salmonella flagellin has unique adjuvant properties that improve SseBmediated protective immunity provided by circulating memory.
AB - The development of a subunit Salmonella vaccine has been hindered by the absence of detailed information about antigenic targets of protective Salmonella-specific T and B cells. Recent studies have identified SseB as a modestly protective Ag in susceptible C57BL/6 mice, but the mechanism of protective immunity remains undefined. In this article, we report that simply combining Salmonella SseB with flagellin substantially enhances protective immunity, allowing immunized C57BL/6 mice to survive for up to 30 d following challenge with virulent bacteria. Surprisingly, the enhancing effect of flagellin did not require flagellin Ag targeting during secondary responses or recognition of flagellin by TLR5. Although coimmunization with flagellin did not affect SseB-specific Ab responses, it modestly boosted CD4 responses. In addition, protective immunity was effectively transferred in circulation to parabionts of immunized mice, demonstrating that tissue-resident memory is not required for vaccine-induced protection. Finally, protective immunity required host expression of IFN-γR but was independent of induced NO synthase expression. Taken together, these data indicate that Salmonella flagellin has unique adjuvant properties that improve SseBmediated protective immunity provided by circulating memory.
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U2 - 10.4049/jimmunol.1601357
DO - 10.4049/jimmunol.1601357
M3 - Article
C2 - 28710253
AN - SCOPUS:85027295470
VL - 199
SP - 1353
EP - 1361
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 4
ER -