<i>Salmonella</i>
            Flagellin Is Not a Dominant Protective Antigen in Oral Immunization with Attenuated Live Vaccine Strains

Kodama, Chie; Matsui, Hidenori

doi:10.1128/iai.72.4.2449-2451.2004

Cited by 21 publications

(21 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In parallel with this repression, flagellin-specific CD4 T cell activation ceases (37) and immunization with flagellin induces only partial protection against low-dose Salmonella challenge infection (36). Furthermore, flagellin is not a dominant protective antigen in immunization with attenuated live Salmonella vaccines (38).…”

Section: Discussionmentioning

confidence: 99%

Antigen selection based on expression levels during infection facilitates vaccine development for an intracellular pathogen

Rollenhagen

Sörensen

Rizos

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Vaccines effective against intracellular pathogens could save the lives of millions of people every year, but vaccine development has been hampered by the slow largely empirical search for protective antigens. In vivo highly expressed antigens might represent a small attractive antigen subset that could be rapidly evaluated, but experimental evidence supporting this rationale, as well as practical strategies for its application, is largely lacking because of technical difficulties. Here, we used Salmonella strains expressing differential amounts of a fluorescent model antigen during infection to show that, in a mouse typhoid fever model, CD4 T cells preferentially recognize abundant Salmonella antigens. To identify a large number of natural Salmonella antigens with high expression levels during infection, we used a quantitative in vivo screening strategy. Immunization studies with five particularly attractive candidates revealed two highly protective antigens that might permit the development of an improved typhoid fever vaccine. In conclusion, we have established a rationale and an experimental strategy that will substantially facilitate vaccine development for Salmonella and possibly other intracellular pathogens.

show abstract

Section: Discussionmentioning

confidence: 99%

Antigen selection based on expression levels during infection facilitates vaccine development for an intracellular pathogen

Rollenhagen

Sörensen

Rizos

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Although there have been reports of full-length flagellin being used to induce the production of anti-flagellar Abs (21,22), there are no reports of full-length TLR5-activating flagellin protecting against subsequent bacterial infection. Indeed, vaccination studies indicate that flagellin-deficient mutant Salmonella induce superior protection when compared with wild-type (WT) parental bacteria (23,24). Yet, when anti-flagellar Abs were raised by immunization with truncated forms of P. aeruginosa flagellin or a component vaccine targeting Campylobacter jejuni flagellin, protection against lethal doses of P. aeruginosa and C. jejuni was again observed (25,26).…”

mentioning

confidence: 99%

Blocking of the TLR5 Activation Domain Hampers Protective Potential of Flagellin DNA Vaccine

Saha

Takeshita

Matsuda

et al. 2007

The Journal of Immunology

View full text Add to dashboard Cite

Flagellin is a key component of the flagella of many pathogens, including Pseudomonas aeruginosa. Flagellin is an attractive vaccine candidate because it is readily produced and manipulated as a recombinant protein and has intrinsic adjuvant activity mediated through TLR5. Although DNA vaccines encoding native Pseudomonas B-type (FliC) or A-type (FlaA) flagellin are strongly immunogenic, the resultant Ab response interferes with the interaction of homologous flagellin with TLR5. This reduces the ability of the host to clear homologous, but not heterologous, flagellin-expressing P. aeruginosa. To circumvent this problem, a DNA vaccine encoding a mutant FliC R90A flagellin was developed. The mutant Ag encoded by this vaccine was highly immunogenic, but its ability to interact with TLR5 was reduced by >100-fold. Vaccination with this flagellin mutant DNA vaccine induced cross-reactive Abs against both FliC and FlaA, but few Abs capable of interfering with TLR5 activation. The flagellin mutant DNA vaccine provided excellent protection against both FliC- and FlaA-expressing P. aeruginosa. These findings suggest that vaccines against flagellated pathogens should avoid inducing Abs against TLR5 and raise the possibility that flagellated bacteria evade host elimination by facilitating the production of Abs that reduce the host’s ability to mount an innate immune response.

show abstract

“…At the same time, here we confirm that the flagellar protein FliD itself is not required for the efficient vaccination of chickens. Although there are several data supporting the role of flagellae in cellular and humoral immune responses to Salmonella (Salazar-Gonzalez and McSorley, 2005), the results of Kodama and Matsui (2004) and Adriaensen et al (2007) also suggest that Salmonella flagellin is not a major protective antigen in mice. As stated above, our results confirm and extend these observations on the lack of a major protective role of S. Enteritidis flagellin against Salmonella infection in chicks.…”

Section: Inhibition (%)mentioning

confidence: 88%

Vaccine potential of a nonflagellated, virulence-plasmid-cured (fliD–, pSEVΔ) mutant of Salmonella Enteritidis for chickens

Imre

Szmolka

Olasz

et al. 2015

Acta Veterinaria Hungarica

View full text Add to dashboard Cite

The aim of these studies was to assess residual virulence and early protective capacity of a negatively markered live attenuated vaccine candidate Salmonella Enteritidis mutant against a highly virulent S. Enteritidis strain using a dayold chicken model. Nonflagellated FliD negative mutants of Salmonella Enteritidis 11 (SE11) with and without the virulence plasmid proved to be sufficiently attenuated (limited invasiveness in vitro/in vivo) without reduced ability to colonise chicken gut. The early protective activity of a nonflagellated, virulence-plasmidcured (fliD-, pSEV∆) mutant against organ invasion, caecal colonisation and faecal shedding by the highly virulent challenge strain S. Enteritidis 147 Nal R proved to be effective and safe. The innate and adaptive immunity was demonstrable during the first four weeks of life, and the serological response was clearly distinguishable from the response induced by the wild parental strain. In conclusion, we provided data for the first time about a virulence-plasmid-cured, nonflagellated mutant of S. Enteritidis to serve as a basis for development of a negatively markered potential live oral vaccine against virulent S. Enteritidis in chicken.

show abstract

Salmonella Flagellin Is Not a Dominant Protective Antigen in Oral Immunization with Attenuated Live Vaccine Strains

Cited by 21 publications

References 17 publications

Antigen selection based on expression levels during infection facilitates vaccine development for an intracellular pathogen

Antigen selection based on expression levels during infection facilitates vaccine development for an intracellular pathogen

Blocking of the TLR5 Activation Domain Hampers Protective Potential of Flagellin DNA Vaccine

Vaccine potential of a nonflagellated, virulence-plasmid-cured (fliD–, pSEVΔ) mutant of Salmonella Enteritidis for chickens

Contact Info

Product

Resources

About