Immunogenicity and antigenic heterogeneity of a human transferrin-binding protein in Neisseria meningitidis

Ferrón, L.; Ferreirós, C.M.; Criado, M.T.; Pintor, M.

doi:10.1128/iai.60.7.2887-2892.1992

Cited by 39 publications

(27 citation statements)

References 35 publications

(32 reference statements)

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“…Investigations of outer membrane proteins as potential vaccine candidates have acquired great importance. Some of these are minor antigens, the transferrin binding proteins TbpA and TbpB [26,27], the 70-kDa protein [28], or the NspA [1]. They are highly conserved, immunogenic in vivo, and able to elicit bactericidal antibodies.…”

Section: Discussionmentioning

confidence: 99%

Antigenic cross-reactivity between outer membrane proteins of Neisseria meningitidis and commensal Neisseria species

Troncoso

2000

FEMS Immunology and Medical Microbiology

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Two mouse sera against outer membrane proteins from a pathogenic Neisseria meningitidis strain and a commensal N. lactamica strain and two human sera from patients recovering from meningococcal meningitis were used to identify antigens common to pathogenic and commensal Neisseria species. Two major antigens of 55 kDa and 32 kDa, present in all N. meningitidis and N. lactamica strains tested, were demonstrable with all the sera used; the 55-kDa protein was iron-regulated. Demonstration of other common antigens was dependent on the serum used: a 65-kDa antigen was visualised with the human and the mouse anti-N. lactamica sera; a 37-kDa antigen identified as the meningococcal ferric binding protein (FbpA) was only detected with the mouse sera, and two antigens of 83 kDa and 15 kDa were only shown with the mouse anti-N. meningitidis serum. The results demonstrate the existence of several outer membrane antigens common to N. lactamica and N. meningitidis strains, in agreement with the hypothesis that natural immunity against meningitis is partially acquired through colonisation by commensal species, and open new perspectives for the design of vaccine formulations and the development of strategies for vaccination against meningitis.

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Section: Discussionmentioning

confidence: 99%

Antigenic cross-reactivity between outer membrane proteins of Neisseria meningitidis and commensal Neisseria species

Troncoso

2000

FEMS Immunology and Medical Microbiology

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“…Titrations of the sera were done by a dot-blot procedure in which 2 txl aliquots of bacterial outer membrane protein suspensions (OMPs) from MH-EDDA cultures, containing 500 /xg of protein, were deposited onto nitrocellulose membranes and probed with serial dilutions of the homologous serum [16]. Mouse immune sera raised against OMPs from the HG7 strain cultured in either human plasma (anti-HG7p serum) or MH-EDDA medium (anti-HG7e serum) were obtained as described previously [10].…”

Section: Immune Seramentioning

confidence: 99%

“…After electrophoresis, proteins were transferred to nitrocellulose membranes using a Milliblot SDE Electroblotting System (Millipore Ib6rica SA) [19]. For immunoblotting [10], the membranes were blocked with Tris-buffered saline (TBS) containing 0.5% skim milk, 0.001% antifoam A and 0.5 g 1-1 Tween 20 (blocking solution), washed once with TBS/Tween 20 and incubated for 1.5 h in blocking solution containing the immune human or mouse sera. After another wash with TBS/Tween 20, they were incubated for 1.5 h with POD-conjugated rabbit 301 IgGs anti-mouse Igs (when testing mouse sera) or with POD-conjugated rabbit IgGs anti-human Igs (when testing human sera).…”

Section: Determination Of Antigenic Profilesmentioning

confidence: 99%

“…In Neisseria meningitidis some of these iron restriction proteins are the components of a specific uptake system to obtain iron from human transferrin (TBP1 and TBP2), whereas others have functions not yet well defined [8][9][10][11][12]. Some recent attempts to produce a vaccine effective against N. meningitidis have focussed on the use of these transferrin (Tf) binding proteins [11,[13][14][15].…”

Section: Introductionmentioning

confidence: 99%

“…Some recent attempts to produce a vaccine effective against N. meningitidis have focussed on the use of these transferrin (Tf) binding proteins [11,[13][14][15]. In previous studies we have demonstrated that TBP2 (the most antigenic protein of the Tf uptake system) is immunogenic both in natural conditions during infection and in vitro in mouse models and, in both cases, it shows similar patterns of antigenic heterogeneity between different strains [10,13]. We have also demonstrated that other outer membrane proteins are antigenic in natural conditions during in vivo infections but not in experimental immunizations in mouse or vice versa [13].…”

Section: Introductionmentioning

confidence: 99%

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Reliability of laboratory models in the analysis of TBP2 and other meningococcal antigens

Ferrón¹

1994

FEMS Immunology and Medical Microbiology

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The lack of experimental models suitable for the study of meningococcal pathogenicity led us to investigate if those actually in use (culture in iron-restricted media and animal models) provide results comparable with the responses observed in vivo during infection. In this work we studied three invasive strains cultured both in laboratory media and in human plasma, analysing the immune responses elicited in mice against membrane antigens and comparing them with those seen using homologous human convalescent sera. Outer membrane protein profiles observed after culture in plasma were different and more complex than those obtained after growth in laboratory media. Analogous differences were observed in the antigenic profiles, detecting some antigens recognized by human, but not mouse sera, and vice versa. However, the response to one of the major iron-regulated outer membrane antigens, the transferrin binding protein 2 (TBP2), was unaffected by the culture medium or the model, human or mouse, used for the analysis. In conclusion, we have found that results of antigenic analysis change depending on the culture conditions and animal models used. For the meningococcal antigen TBP2, growth in iron-restricted laboratory media and a mouse model provide results which correlate well with those observed using convalescent human serum from individuals recovered from infections. We suggest that careful analysis and evaluation of experimental results and their comparison with in vivo elicited immune responses are essential in order to get accurate extrapolations for experimental vaccine designs.

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Patterns of structural and sequence variation within isotype lineages of the Neisseria meningitidis transferrin receptor system

et al. 2015

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Neisseria meningitidis inhabits the human upper respiratory tract and is an important cause of sepsis and meningitis. A surface receptor comprised of transferrin-binding proteins A and B (TbpA and TbpB), is responsible for acquiring iron from host transferrin. Sequence and immunological diversity divides TbpBs into two distinct lineages; isotype I and isotype II. Two representative isotype I and II strains, B16B6 and M982, differ in their dependence on TbpB for in vitro growth on exogenous transferrin. The crystal structure of TbpB and a structural model for TbpA from the representative isotype I N. meningitidis strain B16B6 were obtained. The structures were integrated with a comprehensive analysis of the sequence diversity of these proteins to probe for potential functional differences. A distinct isotype I TbpA was identified that co-varied with TbpB and lacked sequence in the region for the loop 3 α-helix that is proposed to be involved in iron removal from transferrin. The tightly associated isotype I TbpBs had a distinct anchor peptide region, a distinct, smaller linker region between the lobes and lacked the large loops in the isotype II C-lobe. Sequences of the intact TbpB, the TbpB N-lobe, the TbpB C-lobe, and TbpA were subjected to phylogenetic analyses. The phylogenetic clustering of TbpA and the TbpB C-lobe were similar with two main branches comprising the isotype 1 and isotype 2 TbpBs, possibly suggesting an association between TbpA and the TbpB C-lobe. The intact TbpB and TbpB N-lobe had 4 main branches, one consisting of the isotype 1 TbpBs. One isotype 2 TbpB cluster appeared to consist of isotype 1 N-lobe sequences and isotype 2 C-lobe sequences, indicating the swapping of N-lobes and C-lobes. Our findings should inform future studies on the interaction between TbpB and TbpA and the process of iron acquisition.

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Immunogenicity and antigenic heterogeneity of a human transferrin-binding protein in Neisseria meningitidis

Cited by 39 publications

References 35 publications

Antigenic cross-reactivity between outer membrane proteins of Neisseria meningitidis and commensal Neisseria species

Antigenic cross-reactivity between outer membrane proteins of Neisseria meningitidis and commensal Neisseria species

Reliability of laboratory models in the analysis of TBP2 and other meningococcal antigens

Patterns of structural and sequence variation within isotype lineages of the Neisseria meningitidis transferrin receptor system

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