Evidence map›Paper›PMID 26100265›Full record

Trial reportBMC veterinary research2015

Immune response of healthy horses to DNA constructs formulated with a cationic lipid transfection reagent.

Christiane L Schnabel, P Steinig, M Koy, H-J Schuberth, C Juhls, D Oswald, B Wittig, S Willenbrock, H Murua Escobar, C Pfarrer and 5 more

Open access · goldAbstract readRandomized Controlled Trial
In one paragraph

Trial report in BMC veterinary research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.1field-weighted citation impact, top 48% 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

1 citing paper in PubMed, 2 citations in OpenAlex.

  1. Review
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

15 authors at 6 institutions in 3 countries.

Christiane L SchnabelUniversity of Veterinary Medicine Hannover, Clinic for Horses, Buenteweg 9, 30559, Hannover, Germany. Christiane.Schnabel@tiho-hannover.de.
P SteinigUniversity of Veterinary Medicine Hannover, Clinic for Horses, Buenteweg 9, 30559, Hannover, Germany. Patrick.Steinig@tiho-hannover.de.
M KoyUniversity of Veterinary Medicine Hannover, Immunology Unit, Bischofsholer Damm 15, 30173, Hannover, Germany. Mirja.Koy@tiho-hannover.de.
H-J SchuberthUniversity of Veterinary Medicine Hannover, Immunology Unit, Bischofsholer Damm 15, 30173, Hannover, Germany. Hans-Joachim.Schuberth@tiho-hannover.de.
C JuhlsMologen AG, Fabeckstrasse 30, 14195, Berlin, Germany. Juhls@mologen.com.
D OswaldMologen AG, Fabeckstrasse 30, 14195, Berlin, Germany. Oswald@mologen.com.
B WittigFoundation Institute Molecular Biology and Bioinformatics, Freie Universitaet Berlin, Berlin, Germany. burghardt.wittig@fu-berlin.de.
S WillenbrockUniversity of Veterinary Medicine Hannover, Small Animal Clinic, Buenteweg 9, 30559, Hannover, Germany. Saskia.Willenbrock@tiho-hannover.de.
H Murua EscobarUniversity of Veterinary Medicine Hannover, Small Animal Clinic, Buenteweg 9, 30559, Hannover, Germany. hugo.murua.escobar@med.uni-rostock.de.
C PfarrerUniversity of Veterinary Medicine Hannover, Institute of Anatomy, Bischofsholer Damm 15, 30173, Hannover, Germany. Christiane.Pfarrer@tiho-hannover.de.
B WagnerDepartment of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell Universit, 240 Farrier Rd, Ithaca, NY, 14853, USA. bw73@cornell.edu.
P Jaehnigpj statistics, Niedstrasse 16, 12159, Berlin, Germany. peter.jaehnig@pj-statistics.com.
A MoritzDepartment of Veterinary Medicine, Clinical Sciences, Clinical Pathology and Clinical Pathophysiology, Justus-Liebig-Universitaet, Frankfurter Strasse 126, 35392, Giessen, Germany. Andreas.Moritz@vetmed.uni-giessen.de.
K FeigeUniversity of Veterinary Medicine Hannover, Clinic for Horses, Buenteweg 9, 30559, Hannover, Germany. Karsten.Feige@tiho-hannover.de.
J-M V CavalleriUniversity of Veterinary Medicine Hannover, Clinic for Horses, Buenteweg 9, 30559, Hannover, Germany. Jessika.Cavalleri@tiho-hannover.de.
University of Veterinary Medicine Hannover, Foundation · DEMologen (Germany) · DECornell University · USFreie Universität Berlin · DEJustus-Liebig-Universität Gießen · DEUniversidade do Estado do Rio de Janeiro · BR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDeoxyribonucleic acid (DNA) vaccines are used for experimental immunotherapy of equine melanoma. The injection of complexed linear DNA encoding interleukin (IL)-12/IL-18 induced partial tumour remission in a clinical study including 27 grey horses. To date, the detailed mechanism of the anti-tumour effect of this treatment is unknown.

resultsIn the present study, the clinical and cellular responses of 24 healthy horses were monitored over 72 h after simultaneous intradermal and intramuscular application of equine IL-12/IL-18 DNA (complexed with a transfection reagent) or comparative substances (transfection reagent only, nonsense DNA, nonsense DNA depleted of CG). Although the strongest effect was observed in horses treated with expressing DNA, horses in all groups treated with DNA showed systemic responses. In these horses treated with DNA, rectal temperatures were elevated after treatment and serum amyloid A increased. Total leukocyte and neutrophil counts increased, while lymphocyte numbers decreased. The secretion of tumour necrosis factor alpha (TNFα) and interferon gamma (IFNγ) from peripheral mononuclear blood cells ex vivo increased after treatments with DNA, while IL-10 secretion decreased. Horses treated with DNA had significantly higher myeloid cell numbers and chemokine (C-X-C motif) ligand (CXCL)-10 expression in skin samples at the intradermal injection sites compared to horses treated with transfection reagent only, suggesting an inflammatory response to DNA treatment. In horses treated with expressing DNA, however, local CXCL-10 expression was highest and immunohistochemistry revealed more intradermal IL-12-positive cells when compared to the other treatment groups. In contrast to non-grey horses, grey horses showed fewer effects of DNA treatments on blood lymphocyte counts, TNFα secretion and myeloid cell infiltration in the dermis.

conclusionTreatment with complexed linear DNA constructs induced an inflammatory response independent of the coding sequence and of CG motif content. Expressing IL-12/IL-18 DNA locally induces expression of the downstream mediator CXCL-10. The grey horses included appeared to display an attenuated immune response to DNA treatment, although grey horses bearing melanoma responded to this treatment with moderate tumour remission in a preceding study. Whether the different immunological reactivity compared to other horses may contributes to the melanoma susceptibility of grey horses remains to be elucidated.

Indexed as

AnimalsCancer VaccinesCytokinesFemaleGene Expression RegulationHorse DiseasesHorsesInjections, IntradermalInjections, IntramuscularMaleMelanomaRNA, MessengerSerum Amyloid A ProteinVaccines, DNACancer VaccinesCytokinesRNA, MessengerSerum Amyloid A ProteinVaccines, DNA

Identifiers

PMID26100265
PMCPMC4476236
OpenAlexW1755989131

What OpenQuestion holds

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LicenceCC BY
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.