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ABSTRACT
The Gram positive intracellular pathogen Listeria monocytogenes represents a promising vaccine or therapeutic DNA delivery vector that has been successfully administered to humans in clinical trials. However in generating Listeria mutants with therapeutic potential it is important to balance safety attenuation with efficacy. Here we show that L. monocytogenes mutants with a reduced capacity for murine gallbladder replication are capable of stimulating T cell responses in mice and protecting vaccinated animals from secondary challenge. Mutation of L. monocytogenes genes lmo2566 or lmo0598 resulted in significant attenuation in the murine model yet mutants retained a capacity for intracellular growth and stimulation of T cell responses against key Listeria epitopes (LLO91-99 and P60217-225). Importantly the mutants showed a reduced capacity for growth in the gallbladders of vaccinated mice as well as significantly reduced faecal shedding indicating that this approach generates live Listeria-based vector delivery systems with a reduced capacity for the spread of live genetically modified microorganisms into the natural environment.
Disclosure of potential conflicts of interest
The authors declare no conflict of interest
Funding
The authors acknowledge the funding of the APC Microbiome Institute by the Science Foundation of Ireland Centers for Science, Engineering and Technology (CSET) program (Grant Number SFI/12/RC/2273). CGMG is in receipt of funding from the EU FP7 Industry-Academia Partnerships and Pathways (IAPP) through funding of the Vaccines and Imaging Partnership (ViP).