Evidence map›Paper›PMID 26057742›Full record

ArticlePloS one2015

A Mutant Library Approach to Identify Improved Meningococcal Factor H Binding Protein Vaccine Antigens.

Monica Konar, Raffaella Rossi, Helen Walter, Rolando Pajon, Peter T Beernink

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.6field-weighted citation impact, top 19% 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

15 citing papers in PubMed, 17 citations in OpenAlex.

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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

5 authors at 2 institutions in 1 country.

Monica KonarCenter for Immunobiology and Vaccine Development, Children's Hospital Oakland Research Institute, UCSF Benioff Children's Hospital Oakland, Oakland, CA, United States of America.
Raffaella RossiCenter for Immunobiology and Vaccine Development, Children's Hospital Oakland Research Institute, UCSF Benioff Children's Hospital Oakland, Oakland, CA, United States of America.
Helen WalterCenter for Immunobiology and Vaccine Development, Children's Hospital Oakland Research Institute, UCSF Benioff Children's Hospital Oakland, Oakland, CA, United States of America; Biology Department, Mills College, Oakland, CA, United States of America.
Rolando PajonCenter for Immunobiology and Vaccine Development, Children's Hospital Oakland Research Institute, UCSF Benioff Children's Hospital Oakland, Oakland, CA, United States of America.
Peter T BeerninkCenter for Immunobiology and Vaccine Development, Children's Hospital Oakland Research Institute, UCSF Benioff Children's Hospital Oakland, Oakland, CA, United States of America.
UCSF Benioff Children's Hospital · USMills College · US

Funding

CONSTRUCTION OF THE VACCINE CENTERC06RR016226 · NCRR · CHILDREN'S HOSPITAL &RES CTR AT OAKLAND · PI LUCAS, ALEXANDER H. · 2002 to 2002
$2.0M
Improved mutant meningococcal factor H binding protein vaccinesR01AI099125 · NIAID · CHILDREN'S HOSPITAL & RES CTR AT OAKLAND · PI BEERNINK, PETER T. · 2012 to 2015
$1.9M
NCRR NIH HHS C06 RR 016226NCRR NIH HHS C06 RR016226NIAID NIH HHS R01 AI 099125NIAID NIH HHS R01 AI099125
6 · The paper itself

Abstract

Factor H binding protein (FHbp) is a virulence factor used by meningococci to evade the host complement system. FHbp elicits bactericidal antibodies in humans and is part of two recently licensed vaccines. Using human complement Factor H (FH) transgenic mice, we previously showed that binding of FH decreased the protective antibody responses to FHbp vaccination. Therefore, in the present study we devised a library-based method to identify mutant FHbp antigens with very low binding of FH. Using an FHbp sequence variant in one of the two licensed vaccines, we displayed an error-prone PCR mutant FHbp library on the surface of Escherichia coli. We used fluorescence-activated cell sorting to isolate FHbp mutants with very low binding of human FH and preserved binding of control anti-FHbp monoclonal antibodies. We sequenced the gene encoding FHbp from selected clones and introduced the mutations into a soluble FHbp construct. Using this approach, we identified several new mutant FHbp vaccine antigens that had very low binding of FH as measured by ELISA and surface plasmon resonance. The new mutant FHbp antigens elicited protective antibody responses in human FH transgenic mice that were up to 20-fold higher than those elicited by the wild-type FHbp antigen. This approach offers the potential to discover mutant antigens that might not be predictable even with protein structural information and potentially can be applied to other microbial vaccine antigens that bind host proteins.

Indexed as

Gene LibraryAnimalsAntibodies, MonoclonalAntibody FormationAntigens, BacterialBacterial ProteinsCalorimetry, Differential ScanningComplement Factor HEnzyme-Linked Immunosorbent AssayEscherichia coliFemaleHumansImmobilized ProteinsMeningococcal VaccinesMice, TransgenicModels, MolecularAntibodies, MonoclonalAntigens, BacterialBacterial ProteinsCFH protein, humanComplement Factor HImmobilized ProteinsMeningococcal VaccinesMutant ProteinsRecombinant Proteins

Identifiers

PMID26057742
PMCPMC4461315
OpenAlexW584562945

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.