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BMC veterinary research2015; 11; 140; doi: 10.1186/s12917-015-0452-3

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

Abstract: Deoxyribonucleic 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. Results: In 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. Conclusions: Treatment 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.
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Publication Date: 2015-06-23 PubMed ID: 26100265PubMed Central: PMC4476236DOI: 10.1186/s12917-015-0452-3Google Scholar: Lookup
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  • Journal Article
  • Randomized Controlled Trial
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research investigates how healthy horses respond to DNA vaccines intended for the experimental treatment of equine melanoma, particularly focusing on the interleukin (IL)-12/IL-18 DNA. The immune response among healthy horses was observed, and the article suggests a mechanism for the anti-tumor effect of these vaccines.

Introduction and Background

  • The researchers are studying the response to DNA vaccines, which are used experimentally to treat equine melanoma, a type of skin cancer in horses.
  • Previous studies have seen partial tumor remission in grey horses, but so far not much is known about how this treatment works.

Methods of the Study

  • Twenty-four healthy horses were given either interleukin (IL)-12/IL-18 DNA (combined with a transfection agent), transfection reagent only, nonsense DNA, or nonsense DNA depleted of CG, both intradermally and intramuscularly.
  • Rectal temperatures, serum amyloid A levels, leukocyte and neutrophil counts, along with lymphocyte numbers were measured before and after treatment.
  • Ex-vivo secretion of tumour necrosis factor alpha (TNFα), interferon gamma (IFNγ), and IL-10 from peripheral blood mononuclear cells were also observed.
  • Analysis of myeloid cell numbers and chemokine (C-X-C motif) ligand (CXCL)-10 expression in skin samples at the injection sites provided more insights into the local inflammatory reaction to the DNA treatment.

Study Findings

  • All categories of horses treated with DNA experienced systemic responses, including raised body temperatures, increased serum amyloid A, total leukocyte and neutrophil counts, and decreased lymphocyte numbers.
  • The best effects were seen in horses treated with the expressing DNA, in which secretion of TNFα and IFNγ increased while IL-10 secretion decreased.
  • Horses treated with expressing DNA had more myeloid cells and higher CXCL-10 expression at the intradermal injection sites, indicating a robust inflammatory response to the DNA.
  • However, grey horses had a relatively weaker response, exhibiting fewer effects on blood lymphocyte counts, TNFα secretion, and myeloid cell infiltration in the dermis.

Conclusions and Implications

  • Complexed linear DNA constructs elicit an inflammatory response regardless of the coding sequence and CG motif content. Furthermore, IL-12/IL-18 DNA expression locally induces the expression of downstream mediator CXCL-10.
  • The response in grey horses was slightly attenuated, although they had previously exhibited moderate tumor remission following this treatment in other studies.
  • The researchers surmise that the differing immune reactivity in grey horses might contribute to their susceptibility to melanoma, necessitating further investigation.

Cite This Article

APA
Schnabel CL, Steinig P, Koy M, Schuberth HJ, Juhls C, Oswald D, Wittig B, Willenbrock S, Murua Escobar H, Pfarrer C, Wagner B, Jaehnig P, Moritz A, Feige K, Cavalleri JM. (2015). Immune response of healthy horses to DNA constructs formulated with a cationic lipid transfection reagent. BMC Vet Res, 11, 140. https://doi.org/10.1186/s12917-015-0452-3

Publication

BMC veterinary research
ISSN: 1746-6148
NlmUniqueID: 101249759
Country: England
Language: English
Volume: 11
Pages: 140
PII: 140

Researcher Affiliations

Schnabel, Christiane L
  • University of Veterinary Medicine Hannover, Clinic for Horses, Buenteweg 9, 30559, Hannover, Germany. Christiane.Schnabel@tiho-hannover.de.
Steinig, P
  • University of Veterinary Medicine Hannover, Clinic for Horses, Buenteweg 9, 30559, Hannover, Germany. Patrick.Steinig@tiho-hannover.de.
Koy, M
  • University of Veterinary Medicine Hannover, Immunology Unit, Bischofsholer Damm 15, 30173, Hannover, Germany. Mirja.Koy@tiho-hannover.de.
Schuberth, H-J
  • University of Veterinary Medicine Hannover, Immunology Unit, Bischofsholer Damm 15, 30173, Hannover, Germany. Hans-Joachim.Schuberth@tiho-hannover.de.
Juhls, C
  • Mologen AG, Fabeckstrasse 30, 14195, Berlin, Germany. Juhls@mologen.com.
  • Foundation Institute Molecular Biology and Bioinformatics, Freie Universitaet Berlin, Berlin, Germany. Juhls@mologen.com.
Oswald, D
  • Mologen AG, Fabeckstrasse 30, 14195, Berlin, Germany. Oswald@mologen.com.
  • Foundation Institute Molecular Biology and Bioinformatics, Freie Universitaet Berlin, Berlin, Germany. Oswald@mologen.com.
Wittig, B
  • Foundation Institute Molecular Biology and Bioinformatics, Freie Universitaet Berlin, Berlin, Germany. burghardt.wittig@fu-berlin.de.
Willenbrock, S
  • University of Veterinary Medicine Hannover, Small Animal Clinic, Buenteweg 9, 30559, Hannover, Germany. Saskia.Willenbrock@tiho-hannover.de.
Murua Escobar, H
  • University of Veterinary Medicine Hannover, Small Animal Clinic, Buenteweg 9, 30559, Hannover, Germany. hugo.murua.escobar@med.uni-rostock.de.
  • Division of Medicine, Clinic III, Haematology, Oncology and Palliative Medicine, University of Rostock, 18057, Rostock, Germany. hugo.murua.escobar@med.uni-rostock.de.
Pfarrer, C
  • University of Veterinary Medicine Hannover, Institute of Anatomy, Bischofsholer Damm 15, 30173, Hannover, Germany. Christiane.Pfarrer@tiho-hannover.de.
Wagner, B
  • Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell Universit, 240 Farrier Rd, Ithaca, NY, 14853, USA. bw73@cornell.edu.
Jaehnig, P
  • pj statistics, Niedstrasse 16, 12159, Berlin, Germany. peter.jaehnig@pj-statistics.com.
Moritz, A
  • Department 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.
Feige, K
  • University of Veterinary Medicine Hannover, Clinic for Horses, Buenteweg 9, 30559, Hannover, Germany. Karsten.Feige@tiho-hannover.de.
Cavalleri, J-M V
  • University of Veterinary Medicine Hannover, Clinic for Horses, Buenteweg 9, 30559, Hannover, Germany. Jessika.Cavalleri@tiho-hannover.de.

MeSH Terms

  • Animals
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / immunology
  • Cytokines / genetics
  • Cytokines / metabolism
  • Female
  • Gene Expression Regulation / immunology
  • Horse Diseases / immunology
  • Horse Diseases / prevention & control
  • Horses
  • Injections, Intradermal
  • Injections, Intramuscular
  • Male
  • Melanoma / prevention & control
  • Melanoma / veterinary
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Serum Amyloid A Protein / metabolism
  • Vaccines, DNA / immunology

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Citations

This article has been cited 1 times.
  1. Gao W, Pan J, Pan J. Antitumor Activities of Interleukin-12 in Melanoma. Cancers (Basel) 2022 Nov 14;14(22).
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