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Clinical and Vaccine Immunology, November 2009, p. 1529-1537, Vol. 16, No. 11
1071-412X/09/$08.00+0     doi:10.1128/CVI.00153-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Comparative Evaluation of Two Vaccine Candidates against Experimental Leishmaniasis Due to Leishmania major Infection in Four Inbred Mouse Strains{triangledown}

Fouad Benhnini,1,2 Mehdi Chenik,1 Dhafer Laouini,1 Hechmi Louzir,1 Pierre André Cazenave,2 and Koussay Dellagi1*

Laboratoire d'Immuno-Pathologie, Vaccinologie et Génétique Moléculaire, WHO Collaborative Center for Research and Training in Leishmaniasis, and Laboratoire International Associé Ingénierie Biomoléculaire, Centre National de Recherche Scientifique (CNRS), and Institut Pasteur de Tunis, 13 Place Pasteur, BP 74, 1002 Tunis-Belvédère, Tunisia,1 Unité d'Immunophysiopathologie Infectieuse, CNRS URA 1961 and Université Pierre et Marie Curie, Institut Pasteur, 75724 Paris Cedex 15, France2

Received 4 April 2009/ Returned for modification 29 June 2009/ Accepted 27 August 2009

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.

* Corresponding author. Mailing address: Institut Pasteur de Tunis, 13 Place Pasteur, BP 74, 1002 Tunis-Belvédère, Tunisia. Phone: 216 71783022. Fax: 216 71791833. E-mail: koussay.dellagi{at}ird.fr

{triangledown} Published ahead of print on 2 September 2009.

Clinical and Vaccine Immunology, November 2009, p. 1529-1537, Vol. 16, No. 11
1071-412X/09/$08.00+0     doi:10.1128/CVI.00153-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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