Evidence map›Paper›PMID 27668287›Full record

ArticleJCI insight2016

Enhanced protective antibody to a mutant meningococcal factor H-binding protein with low-factor H binding.

Dan M Granoff, Serena Giuntini, Flor A Gowans, Eduardo Lujan, Kelsey Sharkey, Peter T Beernink

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
3.8field-weighted citation impact, top 7% 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

16 citing papers in PubMed, 30 citations in OpenAlex.

  1. Trial
  2. Article
  3. Review
  4. Outsmarting Pathogens with Antibody Engineering.Annual review of chemical and biomolecular engineering · 2023
    Review
  5. Article
  6. Review
  7. Article
  8. Subdominance in Antibody Responses: Implications for Vaccine Development.Microbiology and molecular biology reviews : MMBR · 2020
    Review
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Eliminating Factor H-Binding Activity ofFrontiers in immunology · 2018
    Article
  15. Article
  16. 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.

Dan M Granoff
Serena Giuntini
Flor A Gowans
Eduardo Lujan
Kelsey Sharkey
Peter T Beernink
UCSF Benioff Children's Hospital · US

Funding

National Institute on Aging (NIA) ColonyP51OD011107 · OD · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Simon J. Atkinson · 2012 to 2026
$191.5M
Novel vaccine strategies for prevention of N. meningitidis group B diseaseR01AI046464 · NIAID · OMVAX, INC. · PI MOE, GREGORY ROBERT · 2000 to 2024
$12.1M
The effect of binding of fH to meningococcal fHbp vaccine on antibody protectionR01AI114701 · NIAID · CHILDREN'S HOSPITAL & RES CTR AT OAKLAND · PI BEERNINK, PETER T. · 2015 to 2019
$3.3M
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 RR016226NIAID NIH HHS R01 AI046464NIAID NIH HHS R01 AI099125NIAID NIH HHS R01 AI114701NIH HHS P51 OD011107
6 · The paper itself

Abstract

Meningococcal factor H-binding protein (FHbp) is an antigen in 2 serogroup B meningococcal vaccines. FHbp specifically binds human and some nonhuman primate complement FH. To investigate the effect of binding of FH to FHbp on protective antibody responses, we immunized infant rhesus macaques with either a control recombinant FHbp antigen that bound macaque FH or a mutant antigen with 2 amino acid substitutions and >250-fold lower affinity for FH. The mutant antigen elicited 3-fold higher serum IgG anti-FHbp titers and up to 15-fold higher serum bactericidal titers than the control FHbp vaccine. When comparing sera with similar IgG anti-FHbp titers, the antibodies elicited by the mutant antigen gave greater deposition of complement component C4b on live meningococci (classical complement pathway) and inhibited binding of FH, while the anti-FHbp antibodies elicited by the control vaccine enhanced FH binding. Thus, the mutant FHbp vaccine elicited an anti-FHbp antibody repertoire directed at FHbp epitopes within the FH binding site, which resulted in greater protective activity than the antibodies elicited by the control vaccine, which targeted FHbp epitopes outside of the FH combining site. Binding of a host protein to a vaccine antigen impairs protective antibody responses, which can be overcome with low-binding mutant antigens.

Identifiers

PMID27668287
PMCPMC5033880
OpenAlexW2512359273

What OpenQuestion holds

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Registered trials

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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.