Evidence map›Paper›PMID 21149595›Full record

ArticleInfection and immunity2011

Characterization of diverse subvariants of the meningococcal factor H (fH) binding protein for their ability to bind fH, to mediate serum resistance, and to induce bactericidal antibodies.

Kate L Seib, Brunella Brunelli, Barbara Brogioni, Emmanuelle Palumbo, Stefania Bambini, Alessandro Muzzi, Federica DiMarcello, Sara Marchi, Arie van der Ende, Beatrice Aricó and 6 more

Open access · greenAbstract read
In one paragraph

Article in Infection and immunity, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
6.5field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

44 citing papers in PubMed, 68 citations in OpenAlex.

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  12. TheVaccines · 2020
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  13. Cocrystal structure of meningococcal factor H binding protein variant 3 reveals a new crossprotective epitope recognized by human mAb 1E6.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019
    Article
  14. Emergence of a newProceedings of the National Academy of Sciences of the United States of America · 2017
    Article
  15. Article
  16. Article
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  18. Article
  19. Expression of factor H binding protein in meningococcal strains can vary at least 15-fold and is genetically determined.Proceedings of the National Academy of Sciences of the United States of America · 2016
    Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 3 institutions in 2 countries.

Kate L SeibMolecular Genetics Unit, Novartis Vaccines, Via Fiorentina, 1, 53100 Siena, Italy. Kate.Seib@novartis.com
Brunella Brunelli
Barbara Brogioni
Emmanuelle Palumbo
Stefania Bambini
Alessandro Muzzi
Federica DiMarcello
Sara Marchi
Arie van der Ende
Beatrice Aricó
Silvana Savino
Maria Scarselli
Maurizio Comanducci
Rino Rappuoli
Marzia M Giuliani
Mariagrazia Pizza
Toscana Life Sciences · ITNovartis (Italy) · ITAcademic Medical Center · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Neisseria meningitidis is a commensal of the human nasopharynx but is also a major cause of septicemia and meningitis. The meningococcal factor H binding protein (fHbp) binds human factor H (fH), enabling downregulation of complement activation on the bacterial surface. fHbp is a component of two serogroup B meningococcal vaccines currently in clinical development. Here we characterize 12 fHbp subvariants for their level of surface exposure and ability to bind fH, to mediate serum resistance, and to induce bactericidal antibodies. Flow cytometry and Western analysis revealed that all strains examined expressed fHbp on their surface to different extents and bound fH in an fHbp-dependent manner. However, differences in fH binding did not always correlate with the level of fHbp expression, indicating that this is not the only factor affecting the amount of fH bound. To overcome the issue of strain variability in fHbp expression, the MC58ΔfHbp strain was genetically engineered to express different subvariants from a constitutive heterologous promoter. These recombinant strains were characterized for fH binding, and the data confirmed that each subvariant binds different levels of fH. Surface plasmon resonance revealed differences in the stability of the fHbp-fH complexes that ranged over 2 orders of magnitude, indicating that differences in residues between and within variant groups can influence fH binding. Interestingly, the level of survival in human sera of recombinant MC58 strains expressing diverse subvariants did not correlate with the level of fH binding, suggesting that the interaction of fHbp with fH is not the only function of fHbp that influences serum resistance. Furthermore, cross-reactive bactericidal activity was seen within each variant group, although the degree of activity varied, suggesting that amino acid differences within each variant group influence the bactericidal antibody response.

Indexed as

Amino Acid SequenceAnimalsAntibodies, BacterialBacterial ProteinsComplement Factor HComplement System ProteinsFemaleGenetic VariationHumansMeningococcal InfectionsMiceMolecular Sequence DataNeisseria meningitidisPhylogenyProtein BindingRabbitsAntibodies, BacterialBacterial ProteinsComplement Factor HComplement System Proteins

Identifiers

PMID21149595
PMCPMC3028832
OpenAlexW2122058226

What OpenQuestion holds

Textmetadata
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.