Evidence map›Paper›PMID 21708990›Full record

ArticleInfection and immunity2011

Complement-mediated bactericidal activity of anti-factor H binding protein monoclonal antibodies against the meningococcus relies upon blocking factor H binding.

Serena Giuntini, Donald C Reason, Dan M Granoff

Abstract 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 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
–field-weighted citation impact
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

49 citing papers in PubMed.

  1. Review
  2. Article
  3. Outsmarting Pathogens with Antibody Engineering.Annual review of chemical and biomolecular engineering · 2023
    Review
  4. Review
  5. Review
  6. Article
  7. Article
  8. 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
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Serum Bactericidal Antibody Responses of Students Immunized With a Meningococcal Serogroup B Vaccine in Response to an Outbreak on a University Campus.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2017
    Article
  16. Article
  17. Article
  18. Article
  19. 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

3 authors.

Serena GiuntiniCenter for Immunobiology and Vaccine Development, Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA.
Donald C Reason
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
Structural determinants of human immunity to anthraxR01AI057932 · NIAID · CHILDREN'S HOSPITAL &RES CTR AT OAKLAND · PI REASON, DONALD C · 2004 to 2008
$2.0M
NCRR NIH HHS C06 RR 016226NCRR NIH HHS C06 RR016226NIAID NIH HHS AI 082263NIAID NIH HHS AI57932NIAID NIH HHS R01 AI 046464NIAID NIH HHS R01 AI046464NIAID NIH HHS R01 AI057932NIAID NIH HHS R01 AI082263
6 · The paper itself

Abstract

Binding of the complement-downregulating protein factor H (fH) to the surface of the meningococcus is important for survival of the organism in human serum. The meningococcal vaccine candidate factor H binding protein (fHbp) is an important ligand for human fH. While some fHbp-specific monoclonal antibodies (MAbs) block binding of fH to fHbp, the stoichiometry of blocking in the presence of high serum concentrations of fH and its effect on complement-mediated bactericidal activity are unknown. To investigate this question, we constructed chimeric antibodies in which the human IgG1 constant region was paired with three murine fHbp-specific binding domains designated JAR 3, JAR 5, and MAb502. By surface plasmon resonance, the association rates for binding of all three MAbs to immobilized fHbp were >50-fold higher than that for binding of fH to fHbp, and the MAb dissociation rates were >500-fold lower than that for fH. While all three MAbs elicited similar C1q-dependent C4b deposition on live bacteria (classical complement pathway), only those antibodies that inhibited binding of fH to fHbp (JAR 3 and JAR 5) had bactericidal activity with human complement. MAb502, which did not inhibit fH binding, had complement-mediated bactericidal activity only when tested with fH-depleted human complement. When an IgG1 anti-fHbp MAb binds to sparsely exposed fHbp on the bacterial surface, there appears to be insufficient complement activation for bacteriolysis unless fH binding also is inhibited. The ability of fHbp vaccines to elicit protective antibodies, therefore, is likely to be enhanced if the antibody repertoire is of high avidity and includes fH-blocking activity.

Indexed as

AnimalsAntibodies, MonoclonalAntibody AffinityAntigens, BacterialBacterial ProteinsBacteriolysisCHO CellsComplement ActivationComplement Factor HComplement System ProteinsCricetinaeCricetulusFlow CytometryHumansImmunoglobulin Constant RegionsImmunoglobulin GAntibodies, MonoclonalAntigens, BacterialBacterial ProteinsComplement Factor HComplement System Proteinsfactor H-binding protein, Neisseria meningitidisImmunoglobulin Constant RegionsImmunoglobulin G

Identifiers

PMID21708990
PMCPMC3165461

What OpenQuestion holds

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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.