Dual Immunization with SseB/Flagellin Provides Enhanced Protection against Salmonella Infection Mediated by Circulating Memory Cells

J Immunol. 2017 Aug 15;199(4):1353-1361. doi: 10.4049/jimmunol.1601357. Epub 2017 Jul 14.

Abstract

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 SseB-mediated protective immunity provided by circulating memory.

MeSH terms

  • Adjuvants, Immunologic
  • Animals
  • Antibodies, Bacterial / blood
  • Bacterial Proteins / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • Female
  • Flagellin / immunology*
  • Immunization
  • Immunologic Memory*
  • Mice
  • Mice, Inbred C57BL
  • Molecular Chaperones / immunology*
  • Nitric Oxide Synthase / genetics
  • Nitric Oxide Synthase / metabolism
  • Receptors, Interferon / genetics
  • Receptors, Interferon / immunology
  • Salmonella Infections, Animal / prevention & control*
  • Salmonella Vaccines / administration & dosage
  • Salmonella Vaccines / immunology*
  • Salmonella typhimurium / immunology
  • Toll-Like Receptor 5 / immunology

Substances

  • Adjuvants, Immunologic
  • Antibodies, Bacterial
  • Bacterial Proteins
  • Molecular Chaperones
  • Receptors, Interferon
  • Salmonella Vaccines
  • SseB protein, Salmonella typhimurium
  • Toll-Like Receptor 5
  • interferon gamma receptor
  • Flagellin
  • Nitric Oxide Synthase