Evidence map›Paper›PMID 22064712›Full record

ArticleInfection and immunity2012

Combined roles of human IgG subclass, alternative complement pathway activation, and epitope density in the bactericidal activity of antibodies to meningococcal factor h binding protein.

Serena Giuntini, Donald C Reason, Dan M Granoff

Open access · greenAbstract 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. Cited by 46 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed, 1 pooled it
3.5field-weighted citation impact, top 8% 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

46 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.

  1. Pooled it
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  7. Subclass-switched anti-spike IgG3 oligoclonal cocktails strongly enhance Fc-mediated opsonization.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  8. Review
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  12. C1q binding to surface-bound IgG is stabilized by C1rProceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  13. Article
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  15. Article
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  18. 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
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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

3 authors.

Serena GiuntiniCenter for Immunobiology and Vaccine Development, Children’s Hospital Oakland Research Institute, Oakland, California, 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

Meningococcal vaccines containing factor H binding protein (fHbp) are in clinical development. fHbp binds human fH, which enables the meningococcus to resist complement-mediated bacteriolysis. Previously, we found that chimeric human IgG1 mouse anti-fHbp monoclonal antibodies (MAbs) had human complement-mediated bactericidal activity only if the MAb inhibited fH binding. Since IgG subclasses differ in their ability to activate complement, we investigated the role of human IgG subclasses on antibody functional activity. We constructed chimeric MAbs in which three different murine fHbp-specific binding domains were each paired with human IgG1, IgG2, or IgG3. Against a wild-type group B isolate, all three IgG3 MAbs, irrespective of their ability to inhibit fH binding, had bactericidal activity that was >5-fold higher than the respective IgG1 MAbs, while the IgG2 MAbs had the least activity. Against a mutant with increased fHbp expression, the anti-fHbp MAbs elicited greater C4b deposition (classical pathway) and greater bactericidal activity than against the wild-type strain, and the IgG1 MAbs had similar or greater activity than the respective IgG3 MAbs. The bactericidal activity against both wild-type and mutant strains also was dependent, in part, on activation of the alternative complement pathway. Thus, at lower epitope density in the wild-type strain, the IgG3 anti-fHbp MAbs had the greatest bactericidal activity. At a higher epitope density in the mutant, the IgG1 MAbs had similar or greater bactericidal activity than the IgG3 MAbs, and the activity was less dependent on the inhibition of fH binding than at a lower epitope density.

Indexed as

Blood Bactericidal ActivityComplement ActivationAdultAnimalsAntibodies, BacterialAntibodies, MonoclonalAntigens, BacterialBacterial ProteinsComplement Pathway, AlternativeEpitopesHumansImmunoglobulin GMiceMicrobial ViabilityNeisseria meningitidisAntibodies, BacterialAntibodies, MonoclonalAntigens, BacterialBacterial ProteinsEpitopesfactor H-binding protein, Neisseria meningitidisImmunoglobulin G

Identifiers

PMID22064712
PMCPMC3255668
OpenAlexW2162781391

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.