A vaccine combining two Leishmania braziliensis proteins offers heterologous protection against Leishmania infanturn infection

被引:28
作者
Duarte, Mariana C. [1 ]
Lage, Daniela P. [2 ]
Martins, Vivian T. [3 ]
Costa, Lourena E. [2 ]
Lage, Leticia M. R. [1 ]
Carvalho, Ana Maria R. S. [1 ]
Ludolf, Fernanda [2 ]
Santos, Thais T. O. [2 ]
Roatt, Bruno M. [1 ]
Menezes-Souza, Daniel [1 ]
Fernandes, Ana Paula [4 ]
Tavares, Carlos A. P. [3 ]
Coelho, Eduardo A. F. [1 ,2 ]
机构
[1] Univ Fed Minas Gerais, COLTEC, Dept Patol Clin, Belo Horizonte, MG, Brazil
[2] Univ Fed Minas Gerais, Fac Med, Programa Posgrad Ciencias Saude Infectol & Med Tr, Ave Prof Alfredo Balena 130, BR-30130100 Belo Horizonte, MG, Brazil
[3] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Bioquim & Imunol, Belo Horizonte, MG, Brazil
[4] Univ Fed Minas Gerais, Fac Farm, Dept Anal Clin & Toxicol, Belo Horizonte, MG, Brazil
关键词
Hypothetical proteins; Eukaryotic initiation factor 5a; Heterologous protection; Vaccine; Visceral leishmaniasis; Th1 immune response; INITIATION-FACTOR; 5A; VISCERAL LEISHMANIASIS; TRANSLATION INITIATION; CUTANEOUS LEISHMANIASIS; IMMUNE-RESPONSES; BALB/C MICE; EFFICACY; CHAGASI; SUSCEPTIBILITY; MACROPHAGES;
D O I
10.1016/j.molimm.2016.06.014
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
In the present study, two Leishmania braziliensis proteins, one hypothetical and the eukaryotic initiation factor 5a (EiF5a), were cloned and used as a polyproteins vaccine for the heterologous protection of BALB/c mice against infantum infection. Animals were immunized with the antigens separately or in association, and in both cases saponin was used as an adjuvant. In the results, spleen cells from mice inoculated with the individual or polyproteins vaccine and lately challenged produced significantly higher levels of protein- and parasite-specific IFNI-gamma, IL-12, and GM-CSF, when both a capture ELISA and flow cytometry assays were performed. Evaluating the parasite load by a limiting dilution as well as by RT-PCR, these animals presented significant reductions in the parasite number in all evaluated organs, when compared to the control (saline and saponin) groups. The best protection was reached when the polyproteins vaccine was employed. Protection was associated with the IFN-gamma production against parasite extracts, which was mediated by both CD4* and CD8+ T cells and correlated with the antileishmanial nitrite production. In this context, this vaccine combining two L. braziliensis proteins was able to induce a heterologous protection against VL, and could be considered in future studies to be tested against other Leishmania species or in other mammalian hosts. (C) 2016 Elsevier Ltd. All rights reserved.
引用
收藏
页码:70 / 79
页数:10
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