title: Preclinical safety and tolerability of a repeatedly administered human leishmaniasis DNA vaccine.
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.
authors: MOLOGEN AG, Berlin, Germany.
authors: O
authors: O
authors: Riede
authors: Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK.
authors: K
authors: K
authors: Seifert
authors: MOLOGEN AG, Berlin, Germany.
authors: D
authors: D
authors: Oswald
authors: MOLOGEN AG, Berlin, Germany.
authors: A
authors: A
authors: Endmann
authors: IMGM Laboratories GmbH, Martinsried, Germany.
authors: C
authors: C
authors: Hock
authors: LPT Laboratory of Pharmacology and Toxicology GmbH & Co. KG, Hamburg, Germany.
authors: A
authors: A
authors: Winkler
authors: Animal Health and Veterinary Laboratories Agency, New Haw, Addlestone, UK.
authors: F J
authors: FJ
authors: Salguero
authors: MOLOGEN AG, Berlin, Germany.
authors: M
authors: M
authors: Schroff
authors: Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK.
authors: S L
authors: SL
authors: Croft
authors: MOLOGEN AG, Berlin, Germany.
authors: C
authors: 0000000313574065
authors: C
authors: Juhls
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005822:Genetic Vectors; D007896:Leishmaniasis / Q000276:immunology* / Q000517:prevention & control; D008807:Mice, Inbred BALB C; D017208:Rats, Wistar; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D019444:Vaccines, DNA