Class 1 outer membrane protein of <i>Neisseria meningitidis</i>: epitope analysis of the antigenic diversity between strains, implications for subtype definition and molecular epidemiology

McGuinness, Brian; Lambden, Paul R.; Heckels, John E.

doi:10.1111/j.1365-2958.1993.tb01141.x

Cited by 79 publications

(85 citation statements)

References 22 publications

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“…This region corresponded to loop 7 of the FetA structural model and was previously shown to contain the epitopes for several mouse mAbs (van der . The localization of most variation in an area corresponding to a putative surface-exposed loop on the b-barrel structure of an OMP was redolent of the two major VRs found in the meningococcal PorA porin (Maiden et al, 1991;McGuinness et al, 1990McGuinness et al, , 1993.…”

Section: Discussionmentioning

confidence: 98%

Antigenic diversity of meningococcal enterobactin receptor FetA, a vaccine component

2003

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Meningococcal FetA (FrpB), an iron-regulated outer-membrane protein and vaccine component, was shown to be highly diverse: a total of 60 fetA alleles, encoding 56 protein sequences, were identified from 107 representative Neisseria meningitidis isolates. Phylogenetic analysis established that the allelic variants had been generated by both point mutation and horizontal genetic exchange. Nucleotide substitution was unevenly distributed in the gene, which contained both conserved and variable sequence regions. The most conserved region of the translated peptide sequence corresponded to an amino-terminal domain of the protein and the most diverse region to a previously identified variable region (VR). A nomenclature system for the peptides encoded by the VR was devised which classified 24 variants into 5 FetA variant families. On the basis of these data, murine polyclonal sera specific for four FetA variants were generated. The reactivities of these sera in whole-cell ELISA experiments were consistent with the hypothesis that the VR encoded an immunodominant epitope and indicated that the sera reacted mainly with variants against which they were raised. The diversity of this protein is likely to limit its effectiveness as a vaccine component.

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Section: Discussionmentioning

confidence: 98%

Antigenic diversity of meningococcal enterobactin receptor FetA, a vaccine component

2003

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“…Multiple solid-phase peptide synthesis was carried out with the aid of an Epiguide (Labsystems) using pin technology with a commercially available kit (Cambridge Research Biochemicals) as described in detail previously (Virji & Heckels, 1989;McGuinness et al, 1993). Synthesis used pentafluorophenyl activated esters of N-a-(9-fluorenylmethyloxycarbonyl) (FM0C)-L-amino acids with t-butyl side-chain protection (Milligen), except for arginine (methoxytrimethylphenylsulphonyl sidechain) and serine and threonine, which were used as oxabenzatriazine active esters.…”

Section: Monoclonal Antibodies (Mabs)mentioning

confidence: 99%

Structural comparison and epitope analysis of outer-membrane protein PIA from strains of Neisseria gonorrhoeae with differing serovar specificities

Mee

Thomas

Cooke

et al. 1993

Journal of General Microbiology

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~ ~~The sequences of the por genes, encoding outer-membrane protein PI, have been obtained from a number of strains of Neisseria gonorrhoeae that express PIA molecules with Mering serovar specificities. The inferred amino acid sequences of the mature proteins each comprise 308 residues and show considerable homology, with the degree of sequence variation between PIA molecules being considerably less than seen previously with PIB, but more evenly distributed throughout the molecule. The positions of sequence variation are largely confined to the regions predicted to form one of eight surface-exposed loops, suggesting a more widespread distribution of potential antigenic diversity. The deduced amino acid sequences were used to synthesize peptides for epitope mapping experiments. Some epitopes responsible for serovar specificity or recognized by bactericidal monoclonal antibodies could be identified on the basis of their reactivity with simple linear peptides, whilst others recognized conformational epitopes. By comparison of sequence differences with mAb reactivity it was possible to identify regions that appear to contribute to such determinants, including separated regions of the molecule which together were required for the formation of the conformational epitopes. All the epitopes identified lie at or close to the apices of the predicted surface-exposed loops 1,3,6 or 8, focusing attention on these regions as accessible targets for immune attack.

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“…Antisera reacted specifically with the meningococcal P1.16b subtype B-cell epitope (180TKNTNNNLTL1s9), and also cross-reacted equally well with the P1.16a subtype. Therefore, immunization with BT-MAP induced polyclonal antisera which, in contrast to the P1.16 mAbs (McGuinness e t al., 1993), reacted with peptides containing a minor variation in the subtype epitope. A surprising finding in this study was that both murine and rabbit antisera raised against BT-MAP did not react with the class 1 protein in Western blots.…”

Section: Discussionmentioning

confidence: 99%

“…Structural variations between strains are largely confined to two variable regions VR1 and VR2 which are located in the surface-exposed loops 1 and 4 (McGuinness et al, 1990). Epitope mapping with synthetic peptides has localized the epitopes recognized by the bactericidal, subtype-specific mAbs to the apices of these loops (McGuinness e t al., 1990(McGuinness e t al., , 1993. Thus a mAb with Pl.16a subtype specificity reacted with the peptide TKDTNNNLTL, located at the apex of loop 4.…”

Section: Introductionmentioning

confidence: 99%

Immunization with a multiple antigen peptide containing defined B- and T-cell epitopes: production of bactericidal antibodies against group B Neisseria meningitidis

Christodoulides

Heckels

1994

Microbiology

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Previous analysis of the class 1 outer-membrane (OM) protein of Neisseria meningitidis has identified discrete epitopes to be potential targets for immune attack. The conformation of these epitopes is important for inducing 'n, Southampton, SO18 6YD, UK antibodies which can react with the native protein and promote complementmediated lysis of the meningococcus. The multiple antigen peptide (MAP) system, which consists of an oligomeric branching lysine core to which are attached dendritic arms of defined peptide antigens, confers some conformational stability and also allows for the preparation of immunogens containing both B-cell and T helper (Th)-cell epitopes. In this study, MAPS were synthesized to contain (i) the subtype P1.16b meningococcal class 1 protein Bcell epitope (B-MAP), and (ii) the P1.16b epitope in tandem with a defined Thcell epitope, chosen from tetanus toxin (BT-MAP). The B-MAP was nonimmunogenic in animals. In contrast, incorporation of the Th-cell epitope into BT-MAP induced a strong humoral response towards the class 1 protein B-cell epitope. Antisera from immunized mice and rabbits reacted in ELISA with synthetic peptides containing the B-cell epitope, and also cross-reacted with meningococcal OMS from strains of subtype P1.16b and P1.16a. Murine and rabbit antisera showed similar reactivity and epitope specificity, but did not react with denatured class 1 protein in Western blotting, indicating the predominance of antibodies directed towards conformational epitopes. The antisera from rabbits immunized with BT-MAP promoted complementmediated bactericidal killing not only of the homologous meningococcal subtype P1.16b strain but also of subtype P1.16a.

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Class 1 outer membrane protein of Neisseria meningitidis: epitope analysis of the antigenic diversity between strains, implications for subtype definition and molecular epidemiology

Cited by 79 publications

References 22 publications

Antigenic diversity of meningococcal enterobactin receptor FetA, a vaccine component

Antigenic diversity of meningococcal enterobactin receptor FetA, a vaccine component

Structural comparison and epitope analysis of outer-membrane protein PIA from strains of Neisseria gonorrhoeae with differing serovar specificities

Immunization with a multiple antigen peptide containing defined B- and T-cell epitopes: production of bactericidal antibodies against group B Neisseria meningitidis

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