Evidence map›Paper›PMID 25143339›Full record

ArticleClinical and vaccine immunology : CVI2014

Fusion protein comprising factor H domains 6 and 7 and human IgG1 Fc as an antibacterial immunotherapeutic.

Jutamas Shaughnessy, David M Vu, Rahi Punjabi, Judit Serra-Pladevall, Rosane B DeOliveira, Dan M Granoff, Sanjay Ram

Open access · diamondAbstract read
In one paragraph

Article in Clinical and vaccine immunology : CVI, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
1.1field-weighted citation impact, top 24% 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

26 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. The human factor H protein family - an update.Frontiers in immunology · 2024
    Review
  5. Mechanisms by which Factor H protectsFrontiers in immunology · 2024
    Article
  6. Article
  7. Review
  8. NontypeableJournal of immunology (Baltimore, Md. : 1950) · 2021
    Article
  9. Review
  10. Virulence · 2020
    Article
  11. Review
  12. Review
  13. Antibacterial Fusion Proteins EnhanceFrontiers in immunology · 2020
    Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Human Factor H Domains 6 and 7 Fused to IgG1 Fc Are Immunotherapeutic againstJournal of immunology (Baltimore, Md. : 1950) · 2018
    Article
  19. Frontiers in microbiology · 2018
    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

7 authors at 1 institution in 1 country.

Jutamas ShaughnessyDivision of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
David M VuChildren's Hospital Oakland Research Institute, Oakland, California, USA.
Rahi PunjabiDivision of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Judit Serra-PladevallDivision of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Rosane B DeOliveiraDivision of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Dan M GranoffChildren's Hospital Oakland Research Institute, Oakland, California, USA.
Sanjay RamDivision of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA sanjay.ram@umassmed.edu.
University of Massachusetts Chan Medical School · US

Funding

Novel vaccine strategies for prevention of N. meningitidis group B diseaseR01AI046464 · NIAID · OMVAX, INC. · PI MOE, GREGORY ROBERT · 2000 to 2024
$12.1M
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
Vaccines and Immunotherapeutics against gonorrhea in the contex of Chlamydia coU01AI118161 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI RAM, SANJAY · 2014 to 2017
$2.0M
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 gonorrhoeaeR56AI032725 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI RAM, SANJAY, RICE, PETER A. · 2014 to 2014
$583k
Novel immunotherapeutics against multi-drug resistant Neisseria gonorrhoeaeR21AI111728 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI RAM, SANJAY, SHAUGHNESSY, JUTAMAS · 2014 to 2015
$460k
NCRR NIH HHS C06 RR 016226NCRR NIH HHS C06 RR016226NIAID NIH HHS AI046464NIAID NIH HHS AI054544NIAID NIH HHS AI082263NIAID NIH HHS AI111728NIAID NIH HHS L40 AI057605NIAID NIH HHS R01 AI046464NIAID NIH HHS R01 AI054544NIAID NIH HHS R01 AI082263NIAID NIH HHS R21 AI111728NIAID NIH HHS R56 AI032725NIAID NIH HHS U01 AI118161
6 · The paper itself

Abstract

The emergence of antimicrobial resistance among several medically important pathogens represents a serious threat to human health globally and necessitates the development of novel therapeutics. Complement forms a key arm of innate immune defenses against invading pathogens. A mechanism of complement evasion employed by many pathogens is binding of complement inhibitors, including factor H (FH), a key downregulator of the alternative pathway. Most FH-binding bacteria engage FH through regions in FH spanned by domains 6 and 7 and/or 18 through 20. We created a chimeric protein that comprised human FH domains 6 and 7 fused to human IgG1 Fc (FH6,7/HuFc) and tested its activity as an immunotherapeutic against Neisseria meningitidis, which binds FH through domains 6 and 7. FH6,7/HuFc bound to meningococci and effectively blocked FH binding to bacteria. FH6,7/HuFc enhanced human C3 and C4 deposition and facilitated complement-mediated killing in a dose-responsive manner; complement activation and killing were classical pathway dependent. To investigate in vivo efficacy, infant Wistar rats were treated intraperitoneally (IP) with different doses of FH6,7/HuFc and challenged 2 h later with serogroup C strain 4243 given IP. At 8 to 9 h after the challenge, the FH6,7/HuFc-treated rats had >100-fold fewer CFU per ml of blood than control animals pretreated with phosphate-buffered saline (PBS) or FH18-20/HuFc, which does not bind to meningococci (P < 0.0001). These data provide proof of concept of the utility of FH/Fc fusion proteins as anti-infective immunotherapeutics. Because many microbes share a common binding region(s) in FH, FH/Fc chimeric proteins may be a promising candidate for adjunctive therapy against drug-resistant pathogens.

Indexed as

AnimalsAnti-Bacterial AgentsBloodColony Count, MicrobialComplement Factor HComplement System ProteinsDisease Models, AnimalImmunoglobulin Fc FragmentsImmunoglobulin GImmunotherapyMeningococcal InfectionsMicrobial ViabilityNeisseria meningitidis, Serogroup CRats, WistarRecombinant Fusion ProteinsTreatment OutcomeAnti-Bacterial AgentsComplement Factor HComplement System ProteinsImmunoglobulin Fc FragmentsImmunoglobulin GRecombinant Fusion Proteins

Identifiers

PMID25143339
PMCPMC4266347
OpenAlexW2120366059

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.