title: Immunization against Leishmania major infection using LACK- and IL-12-expressing Lactococcus lactis induces delay in footpad swelling.
abstract: BACKGROUND
  Leishmania is a mammalian parasite affecting over 12 million individuals worldwide. Current treatments are expensive, cause severe side effects, and emerging drug resistance has been reported. Vaccination is the most cost-effective means to control infectious disease but currently there is no vaccine available against Leishmaniasis. Lactococcus lactis is a non-pathogenic, non-colonizing Gram-positive lactic acid bacterium commonly used in the dairy industry. Recently, L. lactis was used to express biologically active molecules including vaccine antigens and cytokines.
  
  
  RESULTS
  We report the generation of L. lactis strains expressing the protective Leishmania antigen, LACK, in the cytoplasm, secreted or anchored to the bacterial cell wall. L. lactis was also engineered to secrete biologically active single chain mouse IL-12. Subcutaneous immunization with live L. lactis expressing LACK anchored to the cell wall and L. lactis secreting IL-12 significantly delayed footpad swelling in Leishmania major infected BALB/c mice. The delay in footpad swelling correlated with a significant reduction of parasite burden in immunized animals compared to control groups. Immunization with these two L. lactis strains induced antigen-specific multifunctional T(H)1 CD4(+) and CD8(+) T cells and a systemic LACK-specific T(H)1 immune response. Further, protection in immunized animals correlated with a Leishmania-specific T(H)1 immune response post-challenge. L. lactis secreting mouse IL-12 was essential for directing immune responses to LACK towards a protective T(H)1 response.
  
  
  CONCLUSIONS
  This report demonstrates the use of L. lactis as a live vaccine against L. major infection in BALB/c mice. The strains generated in this study provide the basis for the development of an inexpensive and safe vaccine against the human parasite Leishmania.
authors.affiliation: Department of Microbiology and Immunology, McGill University, Montréal, Québec, Canada.
authors.forename: Felix
authors.initials: F
authors.lastname: Hugentobler
authors.forename: Karen K
authors.initials: KK
authors.lastname: Yam
authors.forename: Joshua
authors.initials: J
authors.lastname: Gillard
authors.forename: Raya
authors.initials: R
authors.lastname: Mahbuba
authors.forename: Martin
authors.initials: M
authors.lastname: Olivier
authors.forename: Benoit
authors.initials: B
authors.lastname: Cousineau
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000008:administration & dosage* / Q000235:genetics; D001691:Biological Therapy / Q000379:methods*; D007114:Immunization / Q000379:methods*; D018664:Interleukin-12 / Q000008:administration & dosage* / Q000235:genetics; D013294:Lactococcus lactis / Q000235:genetics*; D018320:Leishmania major; D016773:Leishmaniasis, Cutaneous / Q000517:prevention & control / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D030781:Organisms, Genetically Modified; D015800:Protozoan Proteins / Q000008:administration & dosage* / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology
chemical_list: D000953:Antigens, Protozoan; D015800:Protozoan Proteins; C093139:LACK antigen, Leishmania; D018664:Interleukin-12