Chimeric flagellin as the self-adjuvanting antigen for the activation of immune response against Helicobacter pylori

Mori, Jerneja; Vranac, Tanja; Smrekar, Boštjan; Černilec, Maja; Šerbec, Vladka Čurin; Horvat, Simon; Ihan, Alojz; Benčina, Mojca; Jerala, Roman

doi:10.1016/j.vaccine.2012.07.011

Cited by 34 publications

(20 citation statements)

References 37 publications

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“…The human immune system cannot eliminate these bacteria primarily because of the bacterial ability of immune evasion. Although H. pylori flagellin can induce anti-flagellin antibodies in infected patients, it is not recognized by toll-like receptor 5 (TLR5), a member of the toll-like receptor family, which is activated by most bacterial flagellins [1, 54]. One possible reason may be that the flagellins, especially FlaA, are not exposed, and thus cannot be detected in the infected gastric epithelial cells [22].…”

Section: Functions and Pathogenicity Of H Pylori Flagellamentioning

confidence: 99%

Role of Flagella in the Pathogenesis of Helicobacter pylori

2017

Curr Microbiol

140

115

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This review aimed to investigate the role of Helicobacter pylori flagella on the pathogenicity of this bacterium in humans. Helicobacter pylori is a flagellated pathogen that colonizes the human gastroduodenal mucosa and produces inflammation, and is responsible for gastrointestinal disease. Its pathogenesis is attributed to colonization and virulence factors. The primary function of H. pylori flagella is to provide motility. We believe that H. pylori flagella play an important role in the colonization of the gastrointestinal mucosa. Therefore, we reviewed previous studies on flagellar morphology and motility in order to explore the relationship between H. pylori flagella and pathogenicity. Further investigation is required to confirm the association between flagella and pathogenicity in H. pylori.

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Section: Functions and Pathogenicity Of H Pylori Flagellamentioning

confidence: 99%

Role of Flagella in the Pathogenesis of Helicobacter pylori

2017

Curr Microbiol

140

115

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“…If equally efficacious and well tolerated in humans, it could be valuable for moving vaccines forward clinically. An alternate adjuvant strategy is the use of a chimeric flagellin ( H. pylori / E. coli ) engineered to activate TLR5, unlike native H. pylori flagellin . Chimeric flagellin administered prophylactically reduced H. pylori DNA levels significantly, in association with enhanced serum IgG antibody levels; especially when boosts were given with alum.…”

Section: Vaccinesmentioning

confidence: 99%

Inflammation, Immunity, Vaccines for Helicobacter pylori infection

2013

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Over the last decades, it has become evident that chronic infection by Helicobacter pylori is achieved by colonizing an almost exclusive niche and hiding from many of the host's cellular immune defense mechanisms. Although recent years have seen progress in our understanding of the innate and adaptive immune response against H. pylori, it is still uncertain how to promote the development of immunity with the final goal of a successful vaccine. Research published in the last year revealed an intriguing mutual regulation of innate response mechanisms of mucosal epithelial cells by the host and H. pylori, respectively. A further focus was put on the interaction between H. pylori and dendritic cells, with some emphasis on the inflammasome and the resulting T-cell responses. Moreover, the function of microRNAs in macrophages and gastric MALT lymphoma development has been studied in more detail. Several novel antigens and adjuvants have been tested as vaccination strategies, primarily in mice. In this review, we present a concise summary of advances in the area of inflammation, immunity, and vaccines during the last twelve months.While establishing a long-lasting infection, Helicobacter pylori deals with several obstacles of host defense, the harsh stomach environment with its very low pH and sticky mucus, the epithelial layer, which forms the first line of the cellular innate immune response, followed by macrophages and dendritic cells (DCs). Subsequent to the initial epithelial cell responses triggered by the infection, neutrophils and inflammatory monocytes are recruited, followed by the infiltration of adaptive immune cells, mainly T lymphocytes. Here we review recent findings of the past year highlighting the scenario of innate and adaptive immune responses induced by H. pylori.

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“…Because flagellin is a protein, the molecule can be engineered for vaccine development to retain immunogenicity and display foreign epitopes of interest from pathogens such as: influenza (hemagglutinin and matrix proteins) Yersinia pestis, and Helicobacter pylori (FlaA flagellin) (9, 37–41). Compared to the co-administration of flagellin with an antigen, flagellin fusion proteins elicit enhanced humoral responses and are therefore a more alluring alternative for vaccine design (35, 42–45).…”

Section: Introductionmentioning

confidence: 99%

Flagellin Induces Antibody Responses through a TLR5- and Inflammasome-Independent Pathway

López-Yglesias

Zhao

Quarles

et al. 2014

The Journal of Immunology

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Flagellin is a potent immunogen that activates the innate immune system via TLR5 and Naip5/6, and generates strong T and B cell responses. The adaptor protein MyD88 is critical for signaling by TLR5, as well as IL-1 and IL-18 receptors, major downstream mediators of the Naip5/6 Nlrc4-inflammasome. Herein we define roles of known flagellin receptors and MyD88 in antibody responses generated towards flagellin. We used mice genetically deficient in flagellin recognition pathways to characterize innate immune components that regulate isotype specific antibody responses. Using purified flagellin from Salmonella, we dissected the contribution of innate flagellin recognition pathways to promote antibody responses towards flagellin and co-administered ovalbumin in C57BL/6 mice. We demonstrate IgG2c responses towards flagellin were TLR5- and inflammasome-dependent; IgG1 was the dominant isotype and partially TLR5- and inflammasome-dependent. Our data indicates a substantial flagellin-specific IgG1 response was induced through a TLR5-, inflammasome-, and MyD88-independent pathway. IgA anti-FliC responses were TLR5- & MyD88-dependent and caspase-1-independent. Unlike C57BL/6 mice, flagellin immunized A/J mice induced co-dominant IgG1 and IgG2a responses. Furthermore, MyD88-independent flagellin-induced antibody responses were even more pronounced in A/J MyD88−/− mice, and IgA anti-FliC responses were suppressed by MyD88. Flagellin also worked as an adjuvant toward co-administered ovalbumin, but it only promoted IgG1 anti-OVA responses. Our results demonstrate that a novel pathway for flagellin recognition contributes to antibody production. Characterization of this pathway will be useful for understanding immunity to flagellin and the rationale design of flagellin-based vaccines.

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Chimeric flagellin as the self-adjuvanting antigen for the activation of immune response against Helicobacter pylori

Cited by 34 publications

References 37 publications

Role of Flagella in the Pathogenesis of Helicobacter pylori

Role of Flagella in the Pathogenesis of Helicobacter pylori

Inflammation, Immunity, Vaccines for Helicobacter pylori infection

Flagellin Induces Antibody Responses through a TLR5- and Inflammasome-Independent Pathway

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