Evidence map›Paper›PMID 28463232›Full record

ArticleThe Journal of clinical investigation2017

Bispecific antibody targets multiple Pseudomonas aeruginosa evasion mechanisms in the lung vasculature.

Ajitha Thanabalasuriar, Bas Gj Surewaard, Michelle E Willson, Arpan S Neupane, Charles K Stover, Paul Warrener, George Wilson, Ashley E Keller, Bret R Sellman, Antonio DiGiandomenico and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed
4.5field-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

61 citing papers in PubMed, 80 citations in OpenAlex.

  1. Review
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  3. Monoclonal Antibodies Targeting Bacterial Infections: A Broad Review of the Field.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026
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  6. EPY001, a Novel Monoclonal Antibody AgainstInternational journal of molecular sciences · 2025
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  9. 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
  10. Review
  11. Microbiota and Immunity during Respiratory Infections: Lung and Gut Affair.International journal of molecular sciences · 2024
    Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. Outsmarting Pathogens with Antibody Engineering.Annual review of chemical and biomolecular engineering · 2023
    Review
  17. How Three Self-Secreted Biofilm Exopolysaccharides ofInternational journal of molecular sciences · 2023
    Review
  18. Article
  19. Development and validation of a rabbit model ofFrontiers in cellular and infection microbiology · 2023
    Article
  20. Review

1 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 at 1 institution in 1 country.

Ajitha ThanabalasuriarDepartment of Physiology and Pharmacology, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada.
Bas Gj SurewaardDepartment of Physiology and Pharmacology, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada.
Michelle E WillsonDepartment of Physiology and Pharmacology, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada.
Arpan S NeupaneDepartment of Physiology and Pharmacology, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada.
Charles K StoverMedImmune LLC, Gaithersburg, Maryland, USA.
Paul WarrenerMedImmune LLC, Gaithersburg, Maryland, USA.
George WilsonMedImmune LLC, Gaithersburg, Maryland, USA.
Ashley E KellerMedImmune LLC, Gaithersburg, Maryland, USA.
Bret R SellmanMedImmune LLC, Gaithersburg, Maryland, USA.
Antonio DiGiandomenicoMedImmune LLC, Gaithersburg, Maryland, USA.
Paul KubesDepartment of Physiology and Pharmacology, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada.
University of Calgary · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Pseudomonas aeruginosa is a major cause of severe infections that lead to bacteremia and high patient mortality. P. aeruginosa has evolved numerous evasion and subversion mechanisms that work in concert to overcome immune recognition and effector functions in hospitalized and immunosuppressed individuals. Here, we have used multilaser spinning-disk intravital microscopy to monitor the blood-borne stage in a murine bacteremic model of P. aeruginosa infection. P. aeruginosa adhered avidly to lung vasculature, where patrolling neutrophils and other immune cells were virtually blind to the pathogen's presence. This cloaking phenomenon was attributed to expression of Psl exopolysaccharide. Although an anti-Psl mAb activated complement and enhanced neutrophil recognition of P. aeruginosa, neutrophil-mediated clearance of the pathogen was suboptimal owing to a second subversion mechanism, namely the type 3 secretion (T3S) injectisome. Indeed, T3S prevented phagosome acidification and resisted killing inside these compartments. Antibody-mediated inhibition of the T3S protein PcrV did not enhance bacterial phagocytosis but did enhance killing of the few bacteria ingested by neutrophils. A bispecific mAb targeting both Psl and PcrV enhanced neutrophil uptake of P. aeruginosa and also greatly increased inhibition of T3S function, allowing for phagosome acidification and bacterial killing. These data highlight the need to block multiple evasion and subversion mechanisms in tandem to kill P. aeruginosa.

Indexed as

AnimalsAnti-Bacterial AgentsAntibodies, BispecificAntibodies, MonoclonalAntigens, BacterialBacterial LoadBacterial ProteinsBacterial ToxinsComplement System ProteinsDrug Evaluation, PreclinicalFemaleKupffer CellsLungMaleMice, 129 StrainMice, Inbred C57BLAnti-Bacterial AgentsAntibodies, BispecificAntibodies, MonoclonalAntigens, Bacterialantigen V, PseudomonasBacterial ProteinsBacterial ToxinsComplement System ProteinsgremubamabPore Forming Cytotoxic ProteinsReceptors, Fc

Identifiers

PMID28463232
PMCPMC5451222
OpenAlexW2611608829

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.