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Infection and Immunity, October 2005, p. 6372-6382, Vol. 73, No. 10
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.10.6372-6382.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Live Nonpathogenic Parasitic Vector as a Candidate Vaccine against Visceral Leishmaniasis

Marie Breton, Michel J Tremblay, Marc Ouellette, and Barbara Papadopoulou*

Infectious Diseases Research Center, CHUL Research Center of Laval University, and Department of Medical Biology, Faculty of Medicine, Laval University, Quebec G1V 4G2, Canada

Received 4 April 2005/ Returned for modification 7 May 2005/ Accepted 21 June 2005

To date, there are no proven vaccines against any form of leishmaniasis. The development of live attenuated vectors shows promise in the field of Leishmania vaccination because these organisms mimic more effectively the course of real infections and can elicit potent activation of the immune system. In the present study, we investigated the potential of a parasitic protozoan that is nonpathogenic to humans, Leishmania tarentolae, as a live candidate vaccine that efficiently targets dendritic cells and lymphoid organs, thus enhancing antigen presentation and consequently influencing the magnitude and quality of T-cell immune responses. We demonstrated that L. tarentolae activates the dendritic cell maturation process and induces T-cell proliferation and the production of gamma interferon, thus skewing CD4+ T cells toward a Th1 cell phenotype. More importantly, we found that a single intraperitoneal injection of L. tarentolae could elicit a protective immune response against infectious challenge with Leishmania donovani in susceptible BALB/c mice. These results suggest that the use of L. tarentolae as a live vaccine vector may represent a promising approach for improving the effectiveness and safety of candidate live vaccines against Leishmania infections and possibly other intracellular pathogens for which T-cell mediated responses are critical for the development of protective immunity.


* Corresponding author. Mailing address: Infectious Diseases Research Center, CHUL Research Center, CHUQ, 2705 Laurier Blvd., Quebec (QC), Canada G1V 4G2. Phone: (418) 654-2705. Fax: (418) 654-2715. E-mail: barbara.papadopoulou{at}crchul.ulaval.ca.

Editor: W. A. Petri, Jr.


Infection and Immunity, October 2005, p. 6372-6382, Vol. 73, No. 10
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.10.6372-6382.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




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