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

Long-term persistence of vector DNA in tissues can be related to integration into host genomic DNA and thus, theoretically bears tumorigenic potential. However, published data show that the integration rate of plasmid DNA vectors does not exceed the rate of spontaneous mutation events within the host genome. 26, 27, 30 Notably, for linear DNA vectors with a structure similar to MIDGE vectors a very low level of integration has been described. 31 Furthermore and in contrast to closed circular plasmid DNA molecules, integration of covalently closed linear DNA constructs rather leads to disruption of chromosomes followed by apoptosis of affected cells, hence minimizing the risk of replicating unwanted genetic rearrangements. 32 On the basis of these published results, the risk related to potential integration of MIDGE-Th1 vectors into host genomic DNA can be considered as low, though it was not assessed in this work.