Evidence map›Paper›PMID 24841258›Full record

ArticleAntimicrobial agents and chemotherapy2014

A novel anti-PcrV antibody providing enhanced protection against Pseudomonas aeruginosa in multiple animal infection models.

Paul Warrener, Reena Varkey, Jessica C Bonnell, Antonio DiGiandomenico, Maria Camara, Kimberly Cook, Li Peng, Jingying Zha, Partha Chowdury, Bret Sellman and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed
4.4field-weighted citation impact, top 4% 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

66 citing papers in PubMed, 117 citations in OpenAlex.

  1. Review
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  5. Mechanistic blockade ofAntimicrobial agents and chemotherapy · 2025
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  12. Infectious medicine · 2023
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  14. Cells · 2023
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  15. Cells · 2023
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  18. Article
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6 more citing papers are in PubMed but not listed here.

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

11 authors.

Paul WarrenerDepartment of Infectious Diseases, MedImmune, LLC, Gaithersburg, Maryland, USA.
Reena VarkeyAntibody Discovery and Protein Engineering, MedImmune, LLC, Gaithersburg, Maryland, USA.
Jessica C BonnellDepartment of Infectious Diseases, MedImmune, LLC, Gaithersburg, Maryland, USA.
Antonio DiGiandomenicoDepartment of Infectious Diseases, MedImmune, LLC, Gaithersburg, Maryland, USA.
Maria CamaraDepartment of Infectious Diseases, MedImmune, LLC, Gaithersburg, Maryland, USA.
Kimberly CookAntibody Discovery and Protein Engineering, MedImmune, LLC, Gaithersburg, Maryland, USA.
Li PengAntibody Discovery and Protein Engineering, MedImmune, LLC, Gaithersburg, Maryland, USA.
Jingying ZhaDepartment of Infectious Diseases, MedImmune, LLC, Gaithersburg, Maryland, USA.
Partha ChowduryAntibody Discovery and Protein Engineering, MedImmune, LLC, Gaithersburg, Maryland, USA.
Bret SellmanDepartment of Infectious Diseases, MedImmune, LLC, Gaithersburg, Maryland, USA.
C Kendall StoverDepartment of Infectious Diseases, MedImmune, LLC, Gaithersburg, Maryland, USA stoverk@medimmune.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Pseudomonas aeruginosa is a major cause of hospital-acquired infections, particularly in mechanically ventilated patients, and it is the leading cause of death in cystic fibrosis patients. A key virulence factor associated with disease severity is the P. aeruginosa type III secretion system (T3SS), which injects bacterial toxins directly into the cytoplasm of host cells. The PcrV protein, located at the tip of the T3SS injectisome complex, is required for T3SS function and is a well-validated target in animal models of immunoprophylactic strategies targeting P. aeruginosa. In an effort to identify a highly potent and protective monoclonal antibody (MAb) that inhibits the T3SS, we generated and characterized a panel of novel anti-PcrV MAbs. Interestingly, some MAbs exhibiting potent inhibition of T3SS in vitro failed to provide protection in a mouse model of P. aeruginosa infection, suggesting that effective in vivo inhibition of T3SS with anti-PcrV MAbs is epitope dependent. V2L2MD, while not the most potent MAb as assessed by in vitro cytotoxicity inhibition assays, provided strong prophylactic protection in several murine infection models and a postinfection therapeutic model. V2L2MD mediated significantly (P < 0.0001) better in vivo protection than that provided by a comparator antibody, MAb166, a well-characterized anti-PcrV MAb and the progenitor of a clinical candidate, KB001-A. The results described here support further development of a V2L2MD-containing immunotherapeutic and may suggest even greater potential than was previously recognized for the prevention and treatment of P. aeruginosa infections in high-risk populations.

Indexed as

Immunization, PassiveAnimalsAntibodies, BacterialAntibodies, MonoclonalAntigens, BacterialBacterial Secretion SystemsBacterial ToxinsCytotoxicity Tests, ImmunologicDisease Models, AnimalDose-Response Relationship, ImmunologicEpitopesHumansImmunoglobulin Fab FragmentsInjections, IntraperitonealInjections, IntravenousMiceAntibodies, BacterialAntibodies, MonoclonalAntigens, Bacterialantigen V, PseudomonasBacterial Secretion SystemsBacterial ToxinsEpitopesImmunoglobulin Fab FragmentsKB001 antibodyPore Forming Cytotoxic Proteins

Identifiers

PMID24841258
PMCPMC4136058
OpenAlexW2170997653

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.