Type

Journal Article

Authors

Cormac G M Gahan
Colin Hill
Susan A Joyce
Pat G Casey
Mohammed Bahey-El-Din
Georgina C Dowd

Subjects

Microbiology

Topics
platforms replication clinical trials listeria monocytogenes vaccine delivery safety t cell gallbladder

Listeria monocytogenes mutants defective in gallbladder replication represent safety-enhanced vaccine delivery platforms. (2016)

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.
Collections Ireland -> University College Cork -> PubMed

Full list of authors on original publication

Cormac G M Gahan, Colin Hill, Susan A Joyce, Pat G Casey, Mohammed Bahey-El-Din, Georgina C Dowd

Experts in our system

1
Cormac G M Gahan
University College Cork
Total Publications: 109
 
2
Colin Hill
University College Cork
Total Publications: 351
 
3
Susan A. Joyce
University College Cork
Total Publications: 42
 
4
Pat G. Casey
University College Cork
Total Publications: 40
 
5
Mohammed Bahey-El-Din
University College Cork
Total Publications: 8
 
6
Georgina C Dowd
University College Cork
Total Publications: 3