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Variation of the factor H-binding protein of Neisseria meningitidis.

Brehony C, Wilson DJ, Maiden MC - Microbiology (Reading, Engl.) (2009)

Bottom Line: A unified nomenclature scheme was devised to catalogue this diversity.Analysis of recombination and selection on the allele sequences demonstrated that parts of the gene are subject to positive selection, consistent with immune selection on the protein generating antigenic variation, particularly in the C-terminal region of the peptide sequence.The highest levels of selection were observed in regions corresponding to epitopes recognized by previously described bactericidal monoclonal antibodies.

View Article: PubMed Central - PubMed

Affiliation: Department of Zoology, University of Oxford, OX1 3PS, UK. carina.brehony@zoo.ox.ac.uk

ABSTRACT
There is currently no comprehensive meningococcal vaccine, due to difficulties in immunizing against organisms expressing serogroup B capsules. To address this problem, subcapsular antigens, particularly the outer-membrane proteins (OMPs), are being investigated as candidate vaccine components. If immunogenic, however, such antigens are often antigenically variable, and knowledge of the extent and structuring of this diversity is an essential part of vaccine formulation. Factor H-binding protein (fHbp) is one such protein and is included in two vaccines under development. A survey of the diversity of the fHbp gene and the encoded protein in a representative sample of meningococcal isolates confirmed that variability in this protein is structured into two or three major groups, each with a substantial number of alleles that have some association with meningococcal clonal complexes and serogroups. A unified nomenclature scheme was devised to catalogue this diversity. Analysis of recombination and selection on the allele sequences demonstrated that parts of the gene are subject to positive selection, consistent with immune selection on the protein generating antigenic variation, particularly in the C-terminal region of the peptide sequence. The highest levels of selection were observed in regions corresponding to epitopes recognized by previously described bactericidal monoclonal antibodies.

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A 75 % majority-rule consensus clonalframe radial tree of 107 aligned nucleotide sequences with colour coding according to clonal complex and confidence values for nodes. A node is defined as the most recent common ancestor of the isolates in the branch above it.
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f2: A 75 % majority-rule consensus clonalframe radial tree of 107 aligned nucleotide sequences with colour coding according to clonal complex and confidence values for nodes. A node is defined as the most recent common ancestor of the isolates in the branch above it.

Mentions: Genealogical analysis using clonalframe, and phylogenies constructed with neighbour-joining (Supplementary Fig. S2) and maximum-likelihood methods (not shown), resolved protein and nucleotide sequences into two major groups, with the variant 3 isolates branching off from the rest of subfamily A/variant 2 (Fig. 2). clonalframe gives equal weight to genetic events that result in one nucleotide change, and single horizontal genetic exchange events that result in many nucleotide changes, and did not separate the putative subfamily A/variant 3 isolate sequences from the other subfamily A/variant 2 isolates (Fig. 2), although they were more distant from them in neighbour-joining (Supplementary Fig. S2) and maximum-likelihood phylogenies (data not shown).


Variation of the factor H-binding protein of Neisseria meningitidis.

Brehony C, Wilson DJ, Maiden MC - Microbiology (Reading, Engl.) (2009)

A 75 % majority-rule consensus clonalframe radial tree of 107 aligned nucleotide sequences with colour coding according to clonal complex and confidence values for nodes. A node is defined as the most recent common ancestor of the isolates in the branch above it.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2801853&req=5

f2: A 75 % majority-rule consensus clonalframe radial tree of 107 aligned nucleotide sequences with colour coding according to clonal complex and confidence values for nodes. A node is defined as the most recent common ancestor of the isolates in the branch above it.
Mentions: Genealogical analysis using clonalframe, and phylogenies constructed with neighbour-joining (Supplementary Fig. S2) and maximum-likelihood methods (not shown), resolved protein and nucleotide sequences into two major groups, with the variant 3 isolates branching off from the rest of subfamily A/variant 2 (Fig. 2). clonalframe gives equal weight to genetic events that result in one nucleotide change, and single horizontal genetic exchange events that result in many nucleotide changes, and did not separate the putative subfamily A/variant 3 isolate sequences from the other subfamily A/variant 2 isolates (Fig. 2), although they were more distant from them in neighbour-joining (Supplementary Fig. S2) and maximum-likelihood phylogenies (data not shown).

Bottom Line: A unified nomenclature scheme was devised to catalogue this diversity.Analysis of recombination and selection on the allele sequences demonstrated that parts of the gene are subject to positive selection, consistent with immune selection on the protein generating antigenic variation, particularly in the C-terminal region of the peptide sequence.The highest levels of selection were observed in regions corresponding to epitopes recognized by previously described bactericidal monoclonal antibodies.

View Article: PubMed Central - PubMed

Affiliation: Department of Zoology, University of Oxford, OX1 3PS, UK. carina.brehony@zoo.ox.ac.uk

ABSTRACT
There is currently no comprehensive meningococcal vaccine, due to difficulties in immunizing against organisms expressing serogroup B capsules. To address this problem, subcapsular antigens, particularly the outer-membrane proteins (OMPs), are being investigated as candidate vaccine components. If immunogenic, however, such antigens are often antigenically variable, and knowledge of the extent and structuring of this diversity is an essential part of vaccine formulation. Factor H-binding protein (fHbp) is one such protein and is included in two vaccines under development. A survey of the diversity of the fHbp gene and the encoded protein in a representative sample of meningococcal isolates confirmed that variability in this protein is structured into two or three major groups, each with a substantial number of alleles that have some association with meningococcal clonal complexes and serogroups. A unified nomenclature scheme was devised to catalogue this diversity. Analysis of recombination and selection on the allele sequences demonstrated that parts of the gene are subject to positive selection, consistent with immune selection on the protein generating antigenic variation, particularly in the C-terminal region of the peptide sequence. The highest levels of selection were observed in regions corresponding to epitopes recognized by previously described bactericidal monoclonal antibodies.

Show MeSH