title: Comparative evaluation of two vaccine candidates against experimental leishmaniasis due to Leishmania major infection in four inbred mouse strains.
abstract: Experimental leishmaniasis in BALB/c and C57BL/6 mice are the most investigated murine models that were used for the preclinical evaluation of Leishmania vaccine candidates. We have previously described two new inbred mouse strains named PWK and MAI issued from feral founders that also support the development of experimental leishmaniasis due to L. major. In this study, we sought to determine whether different mouse inbred strains generate concordant or discordant results when used to evaluate the potential of Leishmania proteins to protect against experimental leishmaniasis. To this end, two Leishmania proteins, namely, LACK (for Leishmania homolog of receptor for activated C kinase) and LmPDI (for L. major protein disulfide isomerase) were compared for their capacity to protect against experimental leishmaniasis in PWK, MAI, BALB/c, and C57BL/6 inbred mouse strains. Our data show that the capacity of Leishmania proteins to confer protection depends on the mouse strain used, stressing the important role played by the genetic background in shaping the immune response against the pathogen. These results may have important implications for the preclinical evaluation of candidate Leishmania vaccines: rather than using a single mouse strain, a panel of different inbred strains of various genetic backgrounds should be tested in parallel. The antigen that confers protection in the larger range of inbred strains may have better chances to be also protective in outbred human populations and should be selected for clinical trials.
authors.affiliation: Laboratoire d'Immuno-Pathologie, Vaccinologie et Génétique Moléculaire, WHO Collaborative Center for Research and Training in Leishmaniasis, 13 Place Pasteur, BP 74, 1002 Tunis-Belvédére, Tunisia.
authors.forename: Fouad
authors.initials: F
authors.lastname: Benhnini
authors.forename: Mehdi
authors.initials: M
authors.lastname: Chenik
authors.forename: Dhafer
authors.initials: D
authors.lastname: Laouini
authors.forename: Hechmi
authors.initials: H
authors.lastname: Louzir
authors.forename: Pierre André
authors.initials: PA
authors.lastname: Cazenave
authors.forename: Koussay
authors.initials: K
authors.lastname: Dellagi
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D006801:Humans; D018320:Leishmania major / Q000276:immunology*; D007896:Leishmaniasis / Q000276:immunology / Q000517:prevention & control*; D054332:Leishmaniasis Vaccines / Q000276:immunology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D019704:Protein Disulfide-Isomerases / Q000276:immunology; D015800:Protozoan Proteins / Q000276:immunology
chemical_list: D000953:Antigens, Protozoan; D054332:Leishmaniasis Vaccines; D015800:Protozoan Proteins; C093139:LACK antigen, Leishmania; D019704:Protein Disulfide-Isomerases