Enhancement of Host Immune Responses by Oral Vaccination to Salmonella enterica serovar Typhimurium Harboring Both FliC and FljB Flagella

Abstract

Flagellin, the structural component of the flagellar filament in various motile bacteria, can contribute to the activation of NF-κB and proinflammatory cytokine expression during the innate immune response in host cells. Thus, flagellin proteins represent a particularly attractive target for the development of vaccine candidates. In this study, we investigated the immune response by increasing the flagella number in the iacP mutant strain and the adjuvant activity of the flagellin component FljB of Salmonella enterica serovar Typhimurium. We found that the iacP mutant strain expresses two flagellin proteins (FliC and FljB), which result in increased NF-κB-dependent gene expression in bone marrow derived macrophages. Using an oral immunization mouse model, we observed that the administration of a live attenuated S . typhimurium BRD509 strain expressing the FliC and FljB flagellins induced significantly enhanced flagellin-specific IgG responses in the systemic compartment. The mice immunized with the recombinant attenuated S . typhimurium strain that has two types of flagella were protected from lethal challenge with the Salmonella SL1344 strain. These results indicate that overexpression of flagella in the iacP mutant strain enhance the induction of an antigen-specific immune responses in macrophage cell, and both the FliC and FljB flagellar filament proteins-producing S . typhimurium can induce protective immune responses against salmonellosis.

Pseudomonas aeruginosa flagellin as an adjuvant: superiority of a conjugated form of flagellin versus a mixture with a human immunodeficiency virus type 1 vaccine candidate in the induction of immune responses

“…They also found that flagellin may be an efficacious adjuvant for use in humans. However, many studies have shown that FliC as an adjuvant can increase specific antibodies in combination with various vaccines (Eom et al, 2013;Karam et al, 2013;Lee et al, 2006), although we did not achieve this effect. In fact, our results with respect to antibody responses showed a weak effect of FliC on the total antibodies and only an increase in the IgM isotype was observed.…”

Design and expression of peptides with antimicrobial activity againstSalmonellatyphimurium

“…The two flagellin genes, fliC and fljB , are expressed alternately: in phase 2 cells, FljA binds to fliC mRNA, inhibiting its translation, and facilitates its degradation (Yamamoto and Kutsukake, ). Both FliC and FljB flagellar proteins induce protective immune response against salmonella infection (Eom et al ., ). We show that fljB and fliC expressions in Stm(pNUF) are comparable with that of Stm(pBAD) in both growth conditions.…”

Mouse models for assessing the cross-protective efficacy of oral non-typhoidal Salmonella vaccine candidates harbouring in-frame deletions of the ATP-dependent protease lon and other genes

“…In recent years, an increasing number of studies have demonstrated the effectiveness of membrane-anchored flagellin as a mucosal adjuvant, as well as its ability to promote cytokine expression by innate immune cells and trigger the generalized recruitment of T-and B-lymphocytes to secondary lymphoid organs (Mizel & Bates, 2010). For instance, overexpression of flagella has been shown to enhance the induction of an antigen-specific immune response in macrophages and vaccination with a live attenuated strain of S. Typhimurium that produces two flagellin proteins (FliC and FljB) induced protective immune responses against oral challenge with virulent S. Typhimurium (Eom et al, 2013). In addition, S. Enteritidis core and O polysaccharide-FliC glycoconjugates were immunogenic and protective antigens against intraperitoneal challenge with virulent S. Enteritidis in murine models, although the unconjugated NTS core and O polysaccharide were poor immunogens that did not elicit immunological memory (Simon et al, 2011b).…”