Evidence map›Paper›PMID 22734046›Full record

ArticleThe Journal of experimental medicine2012

Identification of broadly protective human antibodies to Pseudomonas aeruginosa exopolysaccharide Psl by phenotypic screening.

Antonio DiGiandomenico, Paul Warrener, Melissa Hamilton, Sandrine Guillard, Peter Ravn, Ralph Minter, Maria Margarita Camara, Vignesh Venkatraman, Randall S Macgill, Jia Lin and 9 more

Registry-linked trialOpen access · bronzeAbstract read
In one paragraph

Article in The Journal of experimental medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07088926 (A Phase IIb Randomized, Double-blind, Placebo-controlled, Parallel, Multidose Study to Evaluate the Efficacy, Safety, and PK of AZD0292 in Participants 12 Years of Age and Older With Bronchiectasis and Chronic Pseudomonas Aeruginosa Colonization), which is not on this map. Cited by 107 papers.

0numbers the graph read from it
0cells of the map it votes in
107citing papers in PubMed
9.1field-weighted citation impact, top 2% 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.

NCT07088926 phase2recruitingnot on this mapstarted 2025, after this paper: background citation

A Phase IIb Randomized, Double-blind, Placebo-controlled, Parallel, Multidose Study to Evaluate the Efficacy, Safety, and PK of AZD0292 in Participants 12 Years of Age and Older With Bronchiectasis and Chronic Pseudomonas Aeruginosa Colonization

TypeinterventionalSponsorAstraZenecaRan2025 to 2028Enrolled435ConditionsBronchiectasis With Pseudomonas Aeruginosa ColonizationArmsAZD0292, Placebo
3 · Its place in the literature

Who cites it

107 citing papers in PubMed, 175 citations in OpenAlex.

  1. Monoclonal Antibodies Targeting Bacterial Infections: A Broad Review of the Field.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026
    Review
  2. Article
  3. Article
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  5. Phage-antibiotic synergy attenuatesFrontiers in cellular and infection microbiology · 2026
    Article
  6. Article
  7. A biofilm-tropiceLife · 2025
    Article
  8. Article
  9. Synthesis of the Pentasaccharide Unit of theMolecules (Basel, Switzerland) · 2025
    Article
  10. Article
  11. Alveolar macrophage function is impaired following inhalation of berry e-cigarette vapor.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  12. Review
  13. Article
  14. Article
  15. Review
  16. Molecular Aspects of the Functioning of Pathogenic Bacteria Biofilm Based onInternational journal of molecular sciences · 2024
    Review
  17. Review
  18. Review
  19. Review
  20. Efficacy of aInfection and immunity · 2023
    Article

47 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

19 authors at 3 institutions in 1 country.

Antonio DiGiandomenicoDepartment of Infectious Diseases, MedImmune, LLC, Gaithersburg, MD 20878, USA.
Paul Warrener
Melissa Hamilton
Sandrine Guillard
Peter Ravn
Ralph Minter
Maria Margarita Camara
Vignesh Venkatraman
Randall S Macgill
Jia Lin
Qun Wang
Ashley Elaine Keller
Jessica C Bonnell
Mladen Tomich
Lutz Jermutus
Michael P McCarthy
David A Melnick
Joann A Suzich
C Kendall Stover
Office of Infectious Diseases · USInfectious Diseases and the Research Institute · USAstraZeneca (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Pseudomonas aeruginosa is a leading cause of hospital-associated infections in the seriously ill, and the primary agent of chronic lung infections in cystic fibrosis patients. A major obstacle to effective control of P. aeruginosa infections is its intrinsic resistance to most antibiotic classes, which results from chromosomally encoded drug-efflux systems and multiple acquired resistance mechanisms selected by years of aggressive antibiotic therapy. These factors demand new strategies and drugs to prevent and treat P. aeruginosa infections. Herein, we describe a monoclonal antibody (mAb) selection strategy on whole P. aeruginosa cells using single-chain variable fragment phage libraries derived from healthy individuals and patients convalescing from P. aeruginosa infections. This approach enabled identification of mAbs that bind three distinct epitopes on the product of the Psl. This exopolysaccharide is important for P. aeruginosa attachment to mammalian cells, and for the formation and maintenance of biofilms produced by nonmucoid and mucoid P. aeruginosa isolates. Functional screens revealed that mAbs to one epitope exhibit superior activity in opsonophagocytic killing and cell attachment assays, and confer significant protection in multiple animal models. Our results indicate that Psl is an accessible serotype-independent surface feature and promising novel protective antigen for preventing P. aeruginosa infections. Furthermore, our mAb discovery strategy holds promise for application to other bacterial pathogens.

Indexed as

AnimalsAntibodies, MonoclonalBacterial AdhesionCell Line, TumorHumansKaplan-Meier EstimateMiceMice, Inbred BALB CMice, Inbred C3HMicrobial ViabilityMutationPeptide LibraryPneumoniaPolysaccharides, BacterialPseudomonas aeruginosaPseudomonas InfectionsAntibodies, Monoclonalexopolysaccharide, PseudomonasPeptide LibraryPolysaccharides, BacterialSingle-Chain Antibodies

Identifiers

PMID22734046
PMCPMC3405507
OpenAlexW2098375088

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
Read underepoch 390

Registered trials

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.