Evidence map›Paper›PMID 22615247›Full record

ArticleInfection and immunity2012

Design of meningococcal factor H binding protein mutant vaccines that do not bind human complement factor H.

Rolando Pajon, Peter T Beernink, Dan M Granoff

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

Article in Infection and immunity, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
2.9field-weighted citation impact, top 10% 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

21 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. A meningococcal vaccine antigen engineered to increase thermal stability and stabilize protective epitopes.Proceedings of the National Academy of Sciences of the United States of America · 2015
    Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Structural vaccinology starts to deliver.Nature reviews. Microbiology · 2012
    Review
  20. Article
4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

3 authors.

Rolando PajonCenter for Immunobiology and Vaccine Development, Children's Hospital Oakland Research Institute, Oakland, California, USA.
Peter T Beernink
Dan M Granoff

Funding

Novel vaccine strategies for prevention of N. meningitidis group B diseaseR01AI046464 · NIAID · OMVAX, INC. · PI MOE, GREGORY ROBERT · 2000 to 2024
$12.1M
An engineered meningococcal OMV vaccine for Africa against all capsular groupsR01AI082263 · NIAID · CHILDREN'S HOSPITAL & RES CTR AT OAKLAND · PI GRANOFF, DAN M. · 2010 to 2013
$2.1M
CONSTRUCTION OF THE VACCINE CENTERC06RR016226 · NCRR · CHILDREN'S HOSPITAL &RES CTR AT OAKLAND · PI LUCAS, ALEXANDER H. · 2002 to 2002
$2.0M
Identification of vaccine antigens based on expression in bloodR01AI070955 · NIAID · CHILDREN'S HOSPITAL & RES CTR AT OAKLAND · PI BEERNINK, PETER T. · 2008 to 2011
$1.6M
NCRR NIH HHS C06 RR016226NCRR NIH HHS C06 RR 16226NIAID NIH HHS R01 AI046464NIAID NIH HHS R01 AI070955NIAID NIH HHS R01 AI082263NIAID NIH HHS R01 AI 46464NIAID NIH HHS R01 AI 70955NIAID NIH HHS R01 AI 82263
6 · The paper itself

Abstract

Meningococcal factor H binding protein (fHbp) is a human species-specific ligand for the complement regulator, factor H (fH). In recent studies, fHbp vaccines in which arginine at position 41 was replaced by serine (R41S) had impaired fH binding. The mutant vaccines elicited bactericidal responses in human fH transgenic mice superior to those elicited by control fHbp vaccines that bound human fH. Based on sequence similarity, fHbp has been classified into three variant groups. Here we report that although R41 is present in fHbp from variant groups 1 and 2, the R41S substitution eliminated fH binding only in variant group 1 proteins. To identify mutants in variant group 2 with impaired fH binding, we generated fHbp structural models and predicted 63 residues influencing fH binding. From these, we created 11 mutants with one or two amino acid substitutions in a variant group 2 protein and identified six that decreased fH binding. Three of these six mutants retained conformational epitopes recognized by all six anti-fHbp monoclonal antibodies (MAbs) tested and elicited serum complement-mediated bactericidal antibody titers in wild-type mice that were not significantly different from those obtained with the control vaccine. Thus, fHbp amino acid residues that affect human fH binding differ across variant groups. This result suggests that fHbp sequence variation induced by immune selection also affects fH binding motifs via coevolution. The three new fHbp mutants from variant group 2, which do not bind human fH, retained important epitopes for eliciting bactericidal antibodies and may be promising vaccine candidates.

Indexed as

Amino Acid SequenceAmino Acid SubstitutionAnimalsArginineBacterial ProteinsComplement Factor HGene Expression Regulation, BacterialHumansMeningococcal InfectionsMeningococcal VaccinesMiceModels, MolecularMutationNeisseria meningitidisProtein BindingProtein ConformationArginineBacterial ProteinsCFH protein, humanComplement Factor HMeningococcal VaccinesSerineVaccines, Synthetic

Identifiers

PMID22615247
PMCPMC3434564
OpenAlexW2137719860

What OpenQuestion holds

Textmetadata
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.