Evaluation of transferrin-binding protein 2 within the transferrin-binding protein complex as a potential antigen for future meningococcal vaccines

Lissolo, Ling; Maitre-Wilmotte, G.; Dumas, Paul; Mignon, M; Danve, B.; Quentin‐Millet, Marie‐José

doi:10.1128/iai.63.3.884-890.1995

Cited by 102 publications

(43 citation statements)

References 49 publications

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“…The interaction between isolated meningococcal Tbps and hTF has been quantitatively characterized for the first time. This has been possible for individual TbpA and TbpB due to the development of a novel purification procedure which preserved the hTF-binding properties of both Tbps, in contrast with previously reported methods [15]. TbpA, TbpB and TbpAjB each bound hTF in solid-and liquid-phase assays.…”

Section: Discussionmentioning

confidence: 95%

Transferrin-binding protein B isolated from Neisseria meningitidis discriminates between apo and diferric human transferrin

Boulton

Gorringe

Allison

et al. 1998

Biochemical Journal

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Neisseria meningitidis utilization of human serum transferrin (hTF)-bound iron is an important pathogenicity determinant. The efficiency of this system would clearly be increased through preferential binding of diferric hTF over the iron-free form. To characterize this process, functionally active meningococcal transferrin-binding protein A (TbpA) and TbpB have been purified from N. meningitidis using a novel purification procedure. The association of isolated Tbps and Tbps in the presence of hTF was investigated by gel filtration. Co-purified TbpA+B formed a complex of molecular mass 300 kDa which bound 1-2 molecules of hTF. Purified TbpA formed a complex of 200 kDa, indicating association as a dimer, whereas TbpB aggregated to form multimers of variable sizes. On recombining TbpA and TbpB, a stable complex of equivalent size to co-purified TbpA+B was formed. This complex may be composed of a single TbpA dimer and 1 molecule of TbpB. The technique of surface plasmon resonance (SPR) was used to demonstrate clearly that TbpB of either high (85 kDa) or low (68 kDa) molecular-mass preferentially bound diferric hTF in comparison with iron-free hTF. This selectivity was not observed with TbpA, but was found at low levels with co-purified TbpA+B. Individual TbpA and TbpB, recombined in a 1:1 molecular ratio, showed iron-mediated discriminatory binding at an intermediate level. SPR was also used to show that TbpA and TbpB bound to distinct regions of hTF, and that prior saturation with TbpB reduced subsequent TbpA binding. The results demonstrated that hTF bound more TbpA than TbpB, with an approximate ratio of 2:1. We have demonstrated that in vitro, TbpA+B exists as a receptor complex composed of a TbpA dimer and one molecule of TbpB, and that TbpB selectively binds diferric hTF. We propose that, in vivo, TbpA and TbpB also exist as a receptor complex, with TbpB selectively binding diferric hTF, bringing it close to TbpA, the transmembrane component, where the ferric iron can be transported to the periplasm.

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Section: Discussionmentioning

confidence: 95%

Transferrin-binding protein B isolated from Neisseria meningitidis discriminates between apo and diferric human transferrin

Boulton

Gorringe

Allison

et al. 1998

Biochemical Journal

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“…For N. meningitidis, it was found that the TbpB proteins could be separated into two families based on sequence and antigenicity (28); however, there are common antigenic domains in the TbpB proteins from N. meningitidis, N. gonorrhoeae, H. influenzae, and A. pleuropneumoniae (17,33). Furthermore, TbpBs from N. meningitidis, H. influenzae, and A. pleuropneumoniae have been demonstrated to be protective antigens in various animal challenge models (1,21,22,29).…”

mentioning

confidence: 99%

The Transferrin Binding Protein B of Moraxella catarrhalis Elicits Bactericidal Antibodies and Is a Potential Vaccine Antigen

Myers¹,

Yang²,

Du³

et al. 1998

Infect Immun

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The transferrin binding protein genes (tbpA and tbpB) from two strains of Moraxella catarrhalis have been cloned and sequenced. The genomic organization of the M. catarrhalis transferrin binding protein genes is unique among known bacteria in that tbpA precedes tbpB and there is a third gene located between them. The deduced sequences of the M. catarrhalis TbpA proteins from two strains were 98% identical, while those of the TbpB proteins from the same strains were 63% identical and 70% similar. The third gene, tentatively called orf3, encodes a protein of approximately 58 kDa that is 98% identical between the two strains. The tbpB genes from four additional strains of M. catarrhalis were cloned and sequenced, and two potential families of TbpB proteins were identified based on sequence similarities. Recombinant TbpA (rTbpA), rTbpB, and rORF3 proteins were expressed in Escherichia coli and purified. rTbpB was shown to retain its ability to bind human transferrin after transfer to a membrane, but neither rTbpA nor rORF3 did. Monospecific anti-rTbpA and anti-rTbpB antibodies were generated and used for immunoblot analysis, which demonstrated that epitopes of M. catarrhalis TbpA and TbpB were antigenically conserved and that there was constitutive expression of the tbp genes. In the absence of an appropriate animal model, anti-rTbpA and anti-rTbpB antibodies were tested for their bactericidal activities. The anti-rTbpA antiserum was not bactericidal, but anti-rTbpB antisera were found to kill heterologous strains within the same family. Thus, if bactericidal ability is clinically relevant, a vaccine comprising multiple rTbpB antigens may protect against M. catarrhalis disease. on July 5, 2020 by guest http://iai.asm.org/ Downloaded from FIG. 2. Nucleotide sequences of the promoter regions of M. catarrhalis 4223 tbpA, orf3, and tbpB genes. (A) Putative promoter elements for tbpA, orf3, and tbpB. RBS, ribosome-binding site. (B) Comparison of Fur-binding sites from E. coli (13), N. meningitidis tbpB (20), H. influenzae tbpB (11), and M. catarrhalis 4223 tbpB. Dots indicate residues identical to the E. coli consensus sequence, and underlining indicates dyad symmetry.

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“…One concern in view of the findings of a previous study [8]using co‐purified TbpA+B was that separation of the proteins to individual TbpA and TbpB had resulted in reduced antigenicity. Unlike the study of Lissolo et al [6], all the separate Tbps used here retained their ability to bind transferrin. Responses to separated TbpA and the co‐purified TbpA+B had high correlation coefficients suggesting that the proportion of antibody positive and negative sera remained the same.…”

Section: Discussionmentioning

confidence: 70%

“…These proteins are expressed by all meningococci and are thought to be involved in iron acquisition from transferrin. They have been shown to elicit protective and bactericidal antibodies to the homologous meningococcal strain in laboratory animals [5, 6]. TbpB has been shown to exhibit antigenic heterogeneity in laboratory animals possibly limiting its vaccine potential [7].…”

Section: Introductionmentioning

confidence: 99%

Analysis of the human Ig isotype response to individual transferrin binding proteins A and B from Neisseria meningitidis

Johnson

Gorringe²,

Fox

et al. 2006

FEMS Immunology &Amp; Medical Microbiology

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Subcapsular antigens, including transferrin binding proteins, are being considered as potential vaccines against serogroup B meningococci. This study examined the human isotype antibody responses in cases of meningococcal disease to meningococcal TbpA (transferrin binding protein A) and TbpB (transferrin binding protein B) from two strains (SD and B16B6) expressing high and low molecular mass TbpB respectively. TbpA isolated from both strains were recognised more frequently and higher durable ELISA absorbance values were detected than those detected against TbpB from either strain. These antibody responses to Tbps were independent of the infecting meningococcal strain type. The antibody response to the four proteins was highly variable between individuals and differed significantly against all four antigens. The variability of immune responses to each Tbp from the two strains suggests that a successful vaccine would need to include TbpA and TbpB from a number of strains.

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Evaluation of transferrin-binding protein 2 within the transferrin-binding protein complex as a potential antigen for future meningococcal vaccines

Cited by 102 publications

References 49 publications

Transferrin-binding protein B isolated from Neisseria meningitidis discriminates between apo and diferric human transferrin

Transferrin-binding protein B isolated from Neisseria meningitidis discriminates between apo and diferric human transferrin

The Transferrin Binding Protein B of Moraxella catarrhalis Elicits Bactericidal Antibodies and Is a Potential Vaccine Antigen

Analysis of the human Ig isotype response to individual transferrin binding proteins A and B from Neisseria meningitidis

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