Prophylactic properties of a Leishmania-specific hypothetical protein in a murine model of visceral leishmaniasis

被引:33
|
作者
Lage, D. P. [1 ]
Martins, V. T. [2 ]
Duarte, M. C. [3 ]
Garde, E. [4 ]
Chavez-Fumagalli, M. A. [1 ]
Menezes-Souza, D. [3 ]
Roatt, B. M. [3 ]
Tavares, C. A. P. [2 ]
Soto, M. [4 ]
Coelho, E. A. F. [1 ]
机构
[1] Univ Fed Minas Gerais, Fac Med, Programa Posgrad Ciencias Saude Infectol & Med Tr, BR-30130100 Belo Horizonte, MG, Brazil
[2] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Bioquim & Imunol, BR-30130100 Belo Horizonte, MG, Brazil
[3] Univ Fed Minas Gerais, COLTEC, Dept Patol Clin, BR-30130100 Belo Horizonte, MG, Brazil
[4] Univ Autonoma Madrid, CSIC UAM, Ctr Biol Mol Severo Ochoa, Dept Biol Mol, Madrid, Spain
关键词
BALBIc mice; experimental vaccine; hypothetical protein; Leishmania infantum; saponin; CONFERS PROTECTIVE IMMUNITY; COLONY-STIMULATING FACTOR; SUSCEPTIBLE BALB/C MICE; CUTANEOUS LEISHMANIASIS; MAJOR INFECTION; AMPHOTERICIN-B; DNA VACCINE; A2; ANTIGEN; DONOVANI; RESPONSES;
D O I
10.1111/pim.12287
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 this work, the effect of vaccination of a newly described Leishmania infantum antigenic protein has been studied in BALB/c mice infected with this parasite species. The LiHyD protein was characterized after a proteomic screening performed with the sera from dogs suffering visceral leishmaniasis (VL). Its recombinant version was expressed, purified and administered to BALB/c mice in combination with saponin. As a result of vaccination and 10weeks after challenge using an infective dose of L.infantum stationary promastigotes, vaccinated mice showed lower parasite burdens in different organs (liver, spleen, bone marrow and footpads' draining lymph nodes) than mice inoculated with the adjuvant alone or the vaccine diluent. Protected mice showed anti-Leishmania IgG2a antibodies and a predominant IL-12-driven IFN- production (mainly produced by CD4(+) T cells) against parasite proteins, whereas unprotected controls showed anti-Leishmania IgG1 antibodies and parasite-mediated IL-4 and IL-10 responses. Vaccinated mice showed an anti-LiHyD IgG2a humoral response, and their spleen cells were able to secrete LiHyD-specific IFN-, IL-12 and GM-CSF cytokines before and after infection. The protection was correlated with the Leishmania-specific production on nitric oxide. Altogether, the results indicate that the new LiHyD protein could be considered in vaccine formulations against VL.
引用
收藏
页码:646 / 656
页数:11
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