Live nonpathogenic parasitic vector as a candidate vaccine against visceral leishmaniasis

被引:114
作者
Breton, M
Tremblay, MJ
Ouellette, M
Papadopoulou, B
机构
[1] Univ Laval, CHUQ, CHUL Res Ctr, Infect Dis Res Ctr, Quebec City, PQ G1V 4G2, Canada
[2] Univ Laval, Fac Med, Dept Med Biol, Quebec City, PQ G1V 4G2, Canada
关键词
D O I
10.1128/IAI.73.10.6372-6382.2005
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:6372 / 6382
页数:11
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