Evidence map›Paper›PMID 25368111›Full record

ArticleInfection and immunity2015

Adenovirus vector expressing Stx1/Stx2-neutralizing agent protects piglets infected with Escherichia coli O157:H7 against fatal systemic intoxication.

Abhineet S Sheoran, Igor P Dmitriev, Elena A Kashentseva, Ocean Cohen, Jean Mukherjee, Michelle Debatis, Jonathan Shearer, Jacqueline M Tremblay, Gillian Beamer, David T Curiel and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Infection and immunity, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.5field-weighted citation impact, top 11% 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

19 citing papers in PubMed, 24 citations in OpenAlex.

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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

12 authors at 2 institutions in 1 country.

Abhineet S SheoranDepartment of Infectious Disease and Global Health, Cummings School of Veterinary Medicine at Tufts University, North Grafton, Massachusetts, USA.
Igor P DmitrievDepartment of Radiation Oncology, Washington University, St. Louis, Missouri, USA.
Elena A KashentsevaDepartment of Radiation Oncology, Washington University, St. Louis, Missouri, USA.
Ocean CohenDepartment of Infectious Disease and Global Health, Cummings School of Veterinary Medicine at Tufts University, North Grafton, Massachusetts, USA.
Jean MukherjeeDepartment of Infectious Disease and Global Health, Cummings School of Veterinary Medicine at Tufts University, North Grafton, Massachusetts, USA.
Michelle DebatisDepartment of Infectious Disease and Global Health, Cummings School of Veterinary Medicine at Tufts University, North Grafton, Massachusetts, USA.
Jonathan ShearerDepartment of Infectious Disease and Global Health, Cummings School of Veterinary Medicine at Tufts University, North Grafton, Massachusetts, USA.
Jacqueline M TremblayDepartment of Infectious Disease and Global Health, Cummings School of Veterinary Medicine at Tufts University, North Grafton, Massachusetts, USA.
Gillian BeamerDepartment of Infectious Disease and Global Health, Cummings School of Veterinary Medicine at Tufts University, North Grafton, Massachusetts, USA.
David T CurielDepartment of Radiation Oncology, Washington University, St. Louis, Missouri, USA.
Charles B ShoemakerDepartment of Infectious Disease and Global Health, Cummings School of Veterinary Medicine at Tufts University, North Grafton, Massachusetts, USA.
Saul TziporiDepartment of Infectious Disease and Global Health, Cummings School of Veterinary Medicine at Tufts University, North Grafton, Massachusetts, USA saul.tzipori@tufts.edu.
Tufts University · USWashington University in St. Louis · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hemolytic-uremic syndrome (HUS), caused by Shiga toxin (Stx)-producing Escherichia coli (STEC), remains untreatable. Production of human monoclonal antibodies against Stx, which are highly effective in preventing Stx sequelae in animal models, is languishing due to cost and logistics. We reported previously that the production and evaluation of a camelid heavy-chain-only VH domain (VHH)-based neutralizing agent (VNA) targeting Stx1 and Stx2 (VNA-Stx) protected mice from Stx1 and Stx2 intoxication. Here we report that a single intramuscular (i.m.) injection of a nonreplicating adenovirus (Ad) vector carrying a secretory transgene of VNA-Stx (Ad/VNA-Stx) protected mice challenged with Stx2 and protected gnotobiotic piglets infected with STEC from fatal systemic intoxication. One i.m. dose of Ad/VNA-Stx prevented fatal central nervous system (CNS) symptoms in 9 of 10 animals when it was given to piglets 24 h after bacterial challenge and in 5 of 9 animals when it was given 48 h after bacterial challenge, just prior to the onset of CNS symptoms. All 6 placebo animals died or were euthanized with severe CNS symptoms. Ad/VNA-Stx treatment had no impact on diarrhea. In conclusion, Ad/VNA-Stx treatment is effective in protecting piglets from fatal Stx2-mediated CNS complications following STEC challenge. With a low production cost and further development, this could presumably be an effective treatment for patients with HUS and/or individuals at high risk of developing HUS due to exposure to STEC.

Indexed as

Adenoviruses, HumanAnimalsAntibodies, NeutralizingDisease Models, AnimalDrug CarriersEscherichia coli InfectionsEscherichia coli O157FemaleGenetic VectorsHemolytic-Uremic SyndromeInjections, IntramuscularMiceShiga Toxin 1Shiga Toxin 2Survival AnalysisSwineAntibodies, NeutralizingDrug CarriersShiga Toxin 1Shiga Toxin 2

Identifiers

PMID25368111
PMCPMC4288880
OpenAlexW2001138774

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.