Evidence map›Paper›PMID 22589720›Full record

ArticlePLoS pathogens2012

The effect of human factor H on immunogenicity of meningococcal native outer membrane vesicle vaccines with over-expressed factor H binding protein.

Peter T Beernink, Jutamas Shaughnessy, Rolando Pajon, Emily M Braga, Sanjay Ram, Dan M Granoff

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
5.6field-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

34 citing papers in PubMed, 44 citations in OpenAlex.

  1. Article
  2. Review
  3. Human and Veterinary Vaccines for Lyme Disease.Current issues in molecular biology · 2021
    Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. 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
  18. Article
  19. Article
  20. Protein Crystallography in Vaccine Research and Development.International journal of molecular sciences · 2015
    Review
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

6 authors at 1 institution in 1 country.

Peter T BeerninkCenter for Immunobiology and Vaccine Development, Children's Hospital Oakland Research Institute, Oakland, California, United States of America.
Jutamas Shaughnessy
Rolando Pajon
Emily M Braga
Sanjay Ram
Dan M Granoff
University of Massachusetts Chan Medical School · US

Funding

The TLR4/MD-2 signaling pathway in gonoccocal diseaseU19AI084048 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI RICE, PETER A. · 2009 to 2013
$13.1M
Novel vaccine strategies for prevention of N. meningitidis group B diseaseR01AI046464 · NIAID · OMVAX, INC. · PI MOE, GREGORY ROBERT · 2000 to 2024
$12.1M
Immunology of Infection with Neisseria gonorrhoeaeR37AI032725 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI RICE, PETER A. · 2004 to 2013
$6.1M
Complement Activation on Neisseria meningitidisR01AI054544 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI RAM, SANJAY · 2004 to 2014
$3.4M
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
IMMUNOLOGY OF INFECTION WITH NEISSERIA GONORRHOEAER01AI032725 · NIAID · BOSTON MEDICAL CENTER · PI RICE, PETER A. · 1993 to 2003
$1.8M
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
Immunology of Infection with Neisseria gonorrhoeaeR56AI032725 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI RAM, SANJAY, RICE, PETER A. · 2014 to 2014
$583k
NCRR NIH HHS C06 RR 016226NCRR NIH HHS C06 RR016226NIAID NIH HHS AI 032725NIAID NIH HHS AI 054544NIAID NIH HHS AI 070955NIAID NIH HHS AI 082263NIAID NIH HHS AI 084048NIAID NIH HHS R01 AI032725NIAID NIH HHS R01 AI 046464NIAID NIH HHS R01 AI046464NIAID NIH HHS R01 AI054544NIAID NIH HHS R01 AI070955NIAID NIH HHS R01 AI082263NIAID NIH HHS R37 AI032725NIAID NIH HHS R56 AI032725NIAID NIH HHS U19 AI084048
6 · The paper itself

Abstract

The binding of human complement inhibitors to vaccine antigens in vivo could diminish their immunogenicity. A meningococcal ligand for the complement down-regulator, factor H (fH), is fH-binding protein (fHbp), which is specific for human fH. Vaccines containing recombinant fHbp or native outer membrane vesicles (NOMV) from mutant strains with over-expressed fHbp are in clinical development. In a previous study in transgenic mice, the presence of human fH impaired the immunogenicity of a recombinant fHbp vaccine. In the present study, we prepared two NOMV vaccines from mutant group B strains with over-expressed wild-type fHbp or an R41S mutant fHbp with no detectable fH binding. In wild-type mice in which mouse fH did not bind to fHbp in either vaccine, the NOMV vaccine with wild-type fHbp elicited 2-fold higher serum IgG anti-fHbp titers (P = 0.001) and 4-fold higher complement-mediated bactericidal titers against a PorA-heterologous strain than the NOMV with the mutant fHbp (P = 0.003). By adsorption, the bactericidal antibodies were shown to be directed at fHbp. In transgenic mice in which human fH bound to the wild-type fHbp but not to the R41S fHbp, the NOMV vaccine with the mutant fHbp elicited 5-fold higher serum IgG anti-fHbp titers (P = 0.002), and 19-fold higher bactericidal titers than the NOMV vaccine with wild-type fHbp (P = 0.001). Thus, in mice that differed only by the presence of human fH, the respective results with the two vaccines were opposite. The enhanced bactericidal activity elicited by the mutant fHbp vaccine in the presence of human fH far outweighed the loss of immunogenicity of the mutant protein in wild-type animals. Engineering fHbp not to bind to its cognate complement inhibitor, therefore, may increase vaccine immunogenicity in humans.

Indexed as

AnimalsAntibodies, BacterialAntigens, BacterialBacterial Outer Membrane ProteinsBacterial ProteinsComplement Factor HFemaleHumansImmunoglobulin GMeningococcal VaccinesMiceMice, Inbred BALB CMice, TransgenicNeisseria meningitidisProtein BindingRecombinant ProteinsAntibodies, BacterialAntigens, BacterialBacterial Outer Membrane ProteinsBacterial ProteinsCFH protein, humanComplement Factor Hfactor H-binding protein, Neisseria meningitidisImmunoglobulin GMeningococcal VaccinesRecombinant Proteins

Identifiers

PMID22589720
PMCPMC3349754
OpenAlexW2022391208

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.