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

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 efficac...

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Autores principales: Riede, O, Seifert, K, Oswald, D, Endmann, A, Hock, C, Winkler, A, Salguero, F J, Schroff, M, Croft, S L, Juhls, C
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4530203/
https://www.ncbi.nlm.nih.gov/pubmed/25871827
http://dx.doi.org/10.1038/gt.2015.35
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author Riede, O
Seifert, K
Oswald, D
Endmann, A
Hock, C
Winkler, A
Salguero, F J
Schroff, M
Croft, S L
Juhls, C
author_facet Riede, O
Seifert, K
Oswald, D
Endmann, A
Hock, C
Winkler, A
Salguero, F J
Schroff, M
Croft, S L
Juhls, C
author_sort Riede, O
collection PubMed
description 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.
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spelling pubmed-45302032015-08-11 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, F J Schroff, M Croft, S L Juhls, C Gene Ther Original Article 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. Nature Publishing Group 2015-08 2015-04-30 /pmc/articles/PMC4530203/ /pubmed/25871827 http://dx.doi.org/10.1038/gt.2015.35 Text en Copyright © 2015 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-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/
spellingShingle Original Article
Riede, O
Seifert, K
Oswald, D
Endmann, A
Hock, C
Winkler, A
Salguero, F J
Schroff, M
Croft, S L
Juhls, C
Preclinical safety and tolerability of a repeatedly administered human leishmaniasis DNA vaccine
title Preclinical safety and tolerability of a repeatedly administered human leishmaniasis DNA vaccine
title_full Preclinical safety and tolerability of a repeatedly administered human leishmaniasis DNA vaccine
title_fullStr Preclinical safety and tolerability of a repeatedly administered human leishmaniasis DNA vaccine
title_full_unstemmed Preclinical safety and tolerability of a repeatedly administered human leishmaniasis DNA vaccine
title_short Preclinical safety and tolerability of a repeatedly administered human leishmaniasis DNA vaccine
title_sort preclinical safety and tolerability of a repeatedly administered human leishmaniasis dna vaccine
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4530203/
https://www.ncbi.nlm.nih.gov/pubmed/25871827
http://dx.doi.org/10.1038/gt.2015.35
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