title: Lactococcus lactis-expressing listeriolysin O (LLO) provides protection and specific CD8(+) T cells against Listeria monocytogenes in the murine infection model.
abstract: Lactococcus lactis has previously been proposed as a vaccine platform for the safe delivery of heterologous antigens. Here we utilized L. lactis as a live vector for expression of listeriolysin O (LLO), a major Listeria monocytogenes antigen and virulence factor. A variety of plasmid constructs were designed to permit either constitutive or nisin-inducible expression of secreted or non-secreted LLO in L. lactis. Recombinant strains were subsequently tested in a murine model for vaccination efficacy against L. monocytogenes infection. CD8(+) T lymphocytes specific for the LLO(91-99) epitope were detected when strains were administered via the intraperitoneal (IP) but not the oral route. Challenge with live L. monocytogenes revealed different levels of protection among the three vaccine strains tested with the nisin-inducible LLO-secreting L. lactis strain providing the greatest protection against secondary infection. This work highlights the usefulness of the GRAS (Generally Regarded As Safe) organism L. lactis as the basis of a live vaccine vector against L. monocytogenes. The work suggests that LLO-expressing L. lactis strains may also have the potential to act as a platform for directing other co-expressed antigens towards the cytosolic MHC class I pathway for enhanced stimulation of the CD8(+) T-cell response.
authors.affiliation: Department of Microbiology, University College Cork, Cork, Ireland.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Bahey-El-Din
authors.forename: Pat G
authors.initials: PG
authors.lastname: Casey
authors.forename: Brendan T
authors.initials: BT
authors.lastname: Griffin
authors.forename: Cormac G M
authors.initials: CG
authors.lastname: Gahan
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D005260:Female; D006360:Heat-Shock Proteins / Q000235:genetics / Q000276:immunology*; D006460:Hemolysin Proteins / Q000235:genetics / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D007263:Infusions, Parenteral; D013294:Lactococcus lactis / Q000235:genetics* / Q000276:immunology; D008089:Listeria monocytogenes / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology* / Q000517:prevention & control; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D013997:Time Factors
chemical_list: D000907:Antibodies, Bacterial; D001427:Bacterial Toxins; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D007074:Immunoglobulin G; C038705:hlyA protein, Listeria monocytogenes