Characterization of a Salmonella typhimurium aro vaccine strain expressing the P.69 antigen of Bordetella pertussis

Strugnell, R A; Dougan, Gordon; Chatfield, Steven N.; Charles, IG; Fairweather, Neil F.; Tite, J P; Li, J; Beesley, Julian E.; Roberts, Mark

doi:10.1128/iai.60.10.3994-4002.1992

Cited by 102 publications

(42 citation statements)

References 48 publications

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“…Tcf belongs to a newly emerging family of proteins defined on the basis of a C-terminal tail that is highly conserved among members of this family. The function of the C-terminal tail of these proteins has not been determined, although it has been reported that the C-terminus of pertactin, the prototype of this family of proteins, may be required for correct secretion across the bacterial cell envelope (Strugell et al, 1992). There are now two Bordetella proteins in addition to pertactin which have this C-terminal domain-the newly recognized BrkA (Fernandez and Weiss, 1994) and Tcf.…”

Section: Discussionmentioning

confidence: 99%

Tracheal colonization factor: a Bordetella pertussis secreted virulence determinant

Finn

Stevens

1995

Molecular Microbiology

110

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We report here the identification of a virulence-associated factor, Tcf, (tracheal colonization factor), produced by strains of Bordetella pertussis but not Bordetella parapertussis or Bordetella bronchiseptica. This protein is encoded by the tcfA gene. When a strain of B. pertussis 18323 lacking this protein is used to infect mice with an aerosol challenge, the number of bacteria isolated from the tracheas is decreased 10-fold when compared with the parent 18323. The derived amino acid sequence of tcfA predicts a 68 kDa RGD-containing, proline-rich protein, which after cleavage of a typical prokaryotic signal sequence would be 64 kDa. Amino acid sequence analysis demonstrates that the C-terminal 30 kDa of this protein shows 50% identity to the 30 kDa C-terminus of another Bordetella protein, the pertactin precursor. The N-terminal 34 kDa region contains the three amino-acid motif RGD and is 16.5% proline. Coupled in vitro transcription and translation analysis indicates that the tcfA gene product migrates as two bands of approximately 90 kDa. A fusion protein of the N-terminal, 34 kDa portion of Tcf to maltose-binding protein migrates, on SDS-PAGE, 30 kDa higher than expected from the combined molecular weights. Polyclonal antisera raised against the unique N-terminal portion of Tcf recognizes 90 kDa and 60 kDa bands in immunoblots of whole-cell lysates of strains of B. pertussis; it does not recognize any protein in whole-cell lysates of B. bronchiseptica or B. parapertussis. Supernatants of cultures of B. pertussis 18323 contain the 60 kDa form of the protein. Southern blot analysis of chromosomal DNA from strains of B. bronchiseptica and B. parapertussis, using a probe derived from tcfA, shows strong hybridization only to B. pertussis DNA. Thus, Tcf appears to be a unique virulence factor of B. pertussis.

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Section: Discussionmentioning

confidence: 99%

Tracheal colonization factor: a Bordetella pertussis secreted virulence determinant

Finn

Stevens

1995

Molecular Microbiology

110

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“…This may result in low expression of the antigen and, as a result, low immunogenicity. For example, Strugnell et al [108] reported increased stability of the gene encoding TetC following insertion into the S. enterica var. Typhimurium chromosome, but the antigen expressed was not immunogenic.…”

Section: Low-level or Unstable Expression Of Heterologous Antigensmentioning

confidence: 99%

vaccines for use in humans: present and future perspectives

Garmory¹,

Brown²,

Titball³

2002

FEMS Microbiology Reviews

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In recent years there has been significant progress in the development of attenuated Salmonella enterica serovar Typhi strains as candidate typhoid fever vaccines. In clinical trials these vaccines have been shown to be well tolerated and immunogenic. For example, the attenuated S. enterica var. Typhi strains CVD 908-htrA (aroC aroD htrA), Ty800 (phoP phoQ) and chi4073 (cya crp cdt) are all promising candidate typhoid vaccines. In addition, clinical trials have demonstrated that S. enterica var. Typhi vaccines expressing heterologous antigens, such as the tetanus toxin fragment C, can induce immunity to the expressed antigens in human volunteers. In many cases, the problems associated with expression of antigens in Salmonella have been successfully addressed and the future of Salmonella vaccine development is very promising.

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“…Oral vaccination with S. Typhimurium S. Typhimurium BRD509, an aroA deletion mutant of S. Typhimurium SL1344 [59], was used as the vaccine strain in all immunisation experiments. The bacterium was grown, without shaking at 37C for 24hrs in 500ml Luria Bertoni broth (LB) [60] containing 25μg/ml streptomycin.…”

Section: Ethics Statementmentioning

confidence: 99%

Vaccination Method Affects Immune Response and Bacterial Growth but Not Protection in the Salmonella Typhimurium Animal Model of Typhoid

Kinnear

Strugnell

2015

PLoS ONE

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Understanding immune responses elicited by vaccines, together with immune responses required for protection, is fundamental to designing effective vaccines and immunisation programs. This study examines the effects of the route of administration of a live attenuated vaccine on its interactions with, and stimulation of, the murine immune system as well as its ability to increase survival and provide protection from colonisation by a virulent challenge strain. We assess the effect of administration method using the murine model for typhoid, where animals are infected with S. Typhimurium. Mice were vaccinated either intravenously or orally with the same live attenuated S. Typhimurium strain and data were collected on vaccine strain growth, shedding and stimulation of antibodies and cytokines. Following vaccination, mice were challenged with a virulent strain of S. Typhimurium and the protection conferred by the different vaccination routes was measured in terms of challenge suppression and animal survival. The main difference in immune stimulation found in this study was the development of a secretory IgA response in orally-vaccinated mice, which was absent in IV vaccinated mice. While both strains showed similar protection in terms of challenge suppression in systemic organs (spleen and liver) as well as survival, they differed in terms of challenge suppression of virulent pathogens in gut-associated organs. This difference in gut colonisation presents important questions around the ability of vaccines to prevent shedding and transmission. These findings demonstrate that while protection conferred by two vaccines can appear to be the same, the mechanisms controlling the protection can differ and have important implications for infection dynamics within a population.

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Characterization of a Salmonella typhimurium aro vaccine strain expressing the P.69 antigen of Bordetella pertussis

Cited by 102 publications

References 48 publications

Tracheal colonization factor: a Bordetella pertussis secreted virulence determinant

Tracheal colonization factor: a Bordetella pertussis secreted virulence determinant

vaccines for use in humans: present and future perspectives

Vaccination Method Affects Immune Response and Bacterial Growth but Not Protection in the Salmonella Typhimurium Animal Model of Typhoid

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