title: The combination of DNA vectors expressing IL-12 + IL-18 elicits high protective immune response against cutaneous leishmaniasis after priming with DNA-p36/LACK and the cytokines, followed by a booster with a vaccinia virus recombinant expressing p36/LACK.
abstract: Protocols of immunization based on the DNA prime/vaccinia virus (VV) boost regime with recombinants expressing relevant antigens have been shown to elicit protection against a variety of pathogens in animal model systems, and various phase I clinical trials have been initiated with this vaccination approach. We have previously shown that mice immunized with a DNA vector expressing p36/LACK of Leishmania infantum followed by a booster with VVp36/LACK induced significant protection against Leishmania major infection. To further improve this protocol of immunization, here we investigated whether the cytokines interleukin-12 (IL-12) and IL-18 could enhance protection against L. major infection in BALB/c mice. We found that priming with DNA vectors expressing p36/LACK and either IL-12 or IL-18, followed by a booster with a VV recombinant expressing the same L. infantum LACK antigen, elicit a higher cellular immune response than by using the same protocol in the absence of the cytokines. The cytokine IL-12 triggered a higher number of IFN-gamma-secreting cells specific for p36 protein than IL-18. When immunized animals were challenged with promastigotes, the highest protection against L. major infection was observed in animals primed with DNAp36 + DNA IL-12 + DNA IL-18 and boosted with VVp36. This protection correlated with a Th1 type of immune response. Our findings revealed that in prime/booster protocols, co-expressing IL-12 and IL-18 during priming is an efficient approach to protect against leishmaniasis. This combined prime/booster immunization regime could have wide use in fighting against parasitic and other infectious diseases.
authors.affiliation: Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, CSIC, Campus Universidad Autónoma, 28049 Madrid, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Tapia
authors.forename: Eva
authors.initials: E
authors.lastname: Pérez-Jiménez
authors.forename: Laura
authors.initials: L
authors.lastname: López-Fuertes
authors.forename: Rosa
authors.initials: R
authors.lastname: Gonzalo
authors.forename: M Magdalena
authors.initials: MM
authors.lastname: Gherardi
authors.forename: Mariano
authors.initials: M
authors.lastname: Esteban
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan; D005260:Female; D005822:Genetic Vectors; D007114:Immunization; D007115:Immunization Schedule; D007117:Immunization, Secondary; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020382:Interleukin-18 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018314:Leishmania infantum / Q000276:immunology; D018320:Leishmania major / Q000472:pathogenicity; D016773:Leishmaniasis, Cutaneous / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics*
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D020382:Interleukin-18; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D019444:Vaccines, DNA; C093139:LACK antigen, Leishmania; D018664:Interleukin-12