title: Expression of two Listeria monocytogenes antigens (P60 and LLO) in Lactococcus lactis and examination for use as live vaccine vectors.
abstract: Listeria monocytogenes is a food-borne intracellular pathogen that mainly infects pregnant and immunocompromised individuals. The pore-forming haemolysin listeriolysin O (LLO), the main virulence factor of Listeria monocytogenes, allows bacteria to escape from the harsh environment of the phagosome to the cytoplasm of the infected cell. This leads to processing of bacterial antigens predominantly through the cytosolic MHC class I presentation pathway. We previously engineered the food-grade bacterium Lactococcus lactis to express LLO and demonstrated an LLO-specific CD8(+) response upon immunization of mice with the engineered L. lactis vaccine strains. In the present work, we examined the immune response and protective efficacy of an L. lactis strain co-expressing LLO and a truncated form of the listerial P60 antigen (tP60). Oral immunization revealed no significant protection against listeriosis with L. lactis expressing LLO, tP60 or the combined LLO/tP60. In contrast, intraperitoneal vaccination induced an LLO-specific CD8(+) immune response with LLO-expressing L. lactis but no significant improvement in protection was observed following vaccination with the combined LLO/tP60 expressing L. lactis strain. This may be due to the low level of tP60 expression in the LLO/tP60 strain. These results demonstrate the necessity for improved oral vaccination strategies using LLO-expressing L. lactis vaccine vectors.
authors.affiliation: Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Alexandria University, Egypt.|Department of Microbiology, University College Cork, Cork, Ireland.|School of Pharmacy, University College Cork, Cork, Ireland.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Bahey-El-Din
authors.affiliation: Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.|Department of Microbiology, University College Cork, Cork, Ireland.
authors.forename: Pat G
authors.initials: PG
authors.lastname: Casey
authors.affiliation: School of Pharmacy, University College Cork, Cork, Ireland.
authors.forename: Brendan T
authors.initials: BT
authors.lastname: Griffin
authors.affiliation: Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.|Department of Microbiology, University College Cork, Cork, Ireland.|School of Pharmacy, University College Cork, Cork, Ireland.
authors.forename: Cormac G M
authors.initials: CGM
authors.lastname: Gahan
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000942:Antigens, Bacterial / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D001427:Bacterial Toxins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes; D015169:Colony Count, Microbial; D005260:Female; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D006460:Hemolysin Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D007274:Injections, Intraperitoneal; D013294:Lactococcus lactis / Q000235:genetics / Q000276:immunology*; D008089:Listeria monocytogenes / Q000276:immunology* / Q000472:pathogenicity; D008088:Listeriosis / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000382:microbiology
chemical_list: C078516:60 kDa protein, Listeria monocytogenes; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; C038705:hlyA protein, Listeria monocytogenes