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Preclinical safety and tolerability of a repeatedly administered human leishmaniasis DNA vaccine

Riede, O, Seifert, K, Oswald, D, Endmann, A, Hock, C, Winkler, A, Salguero, FJ, Schroff, M, Croft, SL and Juhls, C (2015) Preclinical safety and tolerability of a repeatedly administered human leishmaniasis DNA vaccine GENE THERAPY, 22 (8). pp. 628-635.

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Abstract

The leishmaniases are a complex of vector-borne diseases caused by protozoan parasites of the genus Leishmania. LEISHDNAVAX is a multi-antigen, T-cell epitope-enriched DNA vaccine candidate against human leishmaniasis. The vaccine candidate has been proven immunogenic and showed prophylactic efficacy in preclinical studies. Here, we describe the safety testing of LEISHDNAVAX in naive mice and rats, complemented by the demonstration of tolerability in Leishmania-infected mice. Biodistribution and persistence were examined following single and repeated intradermal (i.d.) administration to rats. DNA vectors were distributed systemically but did not accumulate upon repeated injections. Although vector DNA was cleared from most other tissues within 60 days after the last injection, it persisted in skin at the site of injection and in draining lymph nodes. Evaluation of single-dose and repeated-dose toxicity of the vaccine candidate after i.d. administration to naive, non-infected mice did not reveal any safety concerns. LEISHDNAVAX was also well tolerated in Leishmania-infected mice. Taken together, our results substantiate a favorable safety profile of LEISHDNAVAX in both naive and infected animals and thus, support the initiation of clinical trials for both preventive and therapeutic applications of the vaccine.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Veterinary Medicine
Authors :
AuthorsEmailORCID
Riede, OUNSPECIFIEDUNSPECIFIED
Seifert, KUNSPECIFIEDUNSPECIFIED
Oswald, DUNSPECIFIEDUNSPECIFIED
Endmann, AUNSPECIFIEDUNSPECIFIED
Hock, CUNSPECIFIEDUNSPECIFIED
Winkler, AUNSPECIFIEDUNSPECIFIED
Salguero, FJUNSPECIFIEDUNSPECIFIED
Schroff, MUNSPECIFIEDUNSPECIFIED
Croft, SLUNSPECIFIEDUNSPECIFIED
Juhls, CUNSPECIFIEDUNSPECIFIED
Date : 1 August 2015
Identification Number : 10.1038/gt.2015.35
Uncontrolled Keywords : Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Biotechnology & Applied Microbiology, Genetics & Heredity, Medicine, Research & Experimental, Research & Experimental Medicine, DIFFERING PLASMID BACKBONES, ACUTE-RESPIRATORY-SYNDROME, WEST-NILE-VIRUS, IN-VIVO, EXPRESSION CONSTRUCTS, IMMUNE-RESPONSES, GENE-INSERTS, MIDGE VECTOR, BIODISTRIBUTION, INTEGRATION
Related URLs :
Additional Information : This work is licensed under a Creative Commons AttributionNonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http:// creativecommons.org/licenses/by-nc-nd/4.0/
Depositing User : Symplectic Elements
Date Deposited : 08 Jan 2016 11:44
Last Modified : 08 Jan 2016 11:44
URI: http://epubs.surrey.ac.uk/id/eprint/809661

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