A recombinant chimeric protein composed of human and mice-specific CD4+ and CD8+ T-cell epitopes protects against visceral leishmaniasis

被引:39
作者
Martins, V. T. [1 ]
Duarte, M. C. [2 ,3 ]
Lage, D. P. [3 ]
Costa, L. E. [3 ]
Carvalho, A. M. R. S. [2 ]
Mendes, T. A. O. [1 ]
Roatt, B. M. [2 ]
Menezes-Souza, D. [2 ,3 ]
Soto, M. [4 ]
Coelho, E. A. F. [2 ,3 ]
机构
[1] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Bioquim & Imunol, Belo Horizonte, MG, Brazil
[2] Univ Fed Minas Gerais, Fac Med, Programa Posgrad Ciencias Saude Infectol & Med Tr, Belo Horizonte, MG, Brazil
[3] Univ Fed Minas Gerais, COLTEC, Dept Patol Clin, Belo Horizonte, MG, Brazil
[4] Univ Autonoma Madrid, CSIC UAM, Ctr Biol Mol Severo Ochoa, Dept Mol Biol, Madrid, Spain
关键词
immune response; Leishmania infantum; recombinant chimeric protein; T-cell epitopes; vaccine; visceral leishmaniasis; COLONY-STIMULATING FACTOR; IMMUNE-RESPONSES; CUTANEOUS LEISHMANIASIS; HYPOTHETICAL PROTEIN; CONFERS PROTECTION; VACCINE CANDIDATE; DONOVANI; AMAZONENSIS; EFFICACY; SERODIAGNOSIS;
D O I
10.1111/pim.12359
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 study, a recombinant chimeric protein (RCP), which was composed of specific CD4(+) and CD8(+) T-cell epitopes to murine and human haplotypes, was evaluated as an immunogen against Leishmania infantum infection in a murine model. BALB/c mice received saline were immunized with saponin or with RCP with or without an adjuvant. The results showed that RCP/saponin-vaccinated mice presented significantly higher levels of antileishmanial IFN-gamma, IL-12 and GM-CSF before and after challenge, which were associated with the reduction of IL-4 and IL-10 mediated responses. These animals showed significant reductions in the parasite burden in all evaluated organs, when both limiting dilution and quantitative real-time PCR techniques were used. In addition, the protected animals presented higher levels of parasite-specific nitrite, as well as the presence of anti-Leishmania IgG2a isotype antibodies. In conclusion, the RCP/saponin vaccine could be considered as a prophylactic alternative to prevent against VL.
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页数:14
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