Vaccination with the Leishmania major ribosomal proteins plus CpG oligodeoxynucleotides induces protection against experimental cutaneous leishmaniasis in mice

被引:53
|
作者
Iborra, Salvador [3 ]
Parody, Nuria [1 ]
Abanades, Daniel R. [1 ]
Bonay, Pedro [1 ]
Prates, Deboraci [2 ]
Novais, Fernanda O. [2 ]
Barral-Netto, Manoel [2 ]
Alonso, Carlos [1 ]
Soto, Manuel [1 ]
机构
[1] Univ Autonoma Madrid, Fac Ciencias, Dept Biol Mol, Ctr Biol Mol Severo Ochoa, E-28049 Madrid, Spain
[2] Fundacao Oswaldo Cruz FIOCRUZ, Ctr Pesquisas Goncalo Moniz, BR-296710 Salvador, BA, Brazil
[3] Inst Salud Carlos III, Ctr Nacl Microbiol, Unidad Inmunol Viral, Madrid 28220, Spain
关键词
Leishmania; BALB/C mice; C57BL/6; mice; Th1/Th2 immune responses; Ribosomal proteins; Vaccines;
D O I
10.1016/j.micinf.2008.06.002
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
In the present work we analyze the antigenicity of Leishmania major ribosomal proteins (LRP) in infected BALB/c mice. We show that BALB/c mice vaccinated with LRP in the presence of CpG oligodeoxynucleotides (CpG-ODN) were protected against the development of dermal pathology and showed a reduction in the parasite load after challenge with L. major. This protection was associated with the induction of an IL-12 dependent specific-IFN-gamma response mediated mainly by CD4(+) T cell, albeit a minor contribution of CD8(+) T cells cannot be ruled out. Induction of Th1 responses against LRP also resulted in a reversion of the Th2 responses associated with susceptibility. A marked reduction of IgG1 antibody titer against parasite antigens besides an impaired IL-4 and IL-10 cytokine production by parasite specific T cells was observed. In addition, we show that the administration of the LRP plus CpG-ODN preparation also conferred protection in the naturally resistant C57BL/6 mice. In this strain protection was associated with a LRP specific IFN-gamma production in lymph nodes draining the challenge site. We believe that these evolutionary conserved proteins, combined with adjuvants that favor Th1 responses, may be relevant components of a pan-Leishmania vaccine. (c) 2008 Elsevier Masson SAS. All rights reserved.
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页码:1133 / 1141
页数:9
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