Costa-Pereira Christiane, Moreira Marcela L, Soares Rodrigo P, Marteleto Bruno H, Ribeiro Vitor M, França-Dias Michelle H, Cardoso Ludmila M, Viana Kelvinson F, Giunchetti Rodolfo C, Martins-Filho Olindo A, Araújo Márcio S S
Laboratório de Biomarcadores de Diagnóstico e Monitoração, Centro de Pesquisas René Rachou/FIOCRUZ - MG, Av. Augusto de Lima, 1715, 30190-002, Belo Horizonte, MG, Brazil.
Clínica Veterinária Santo Agostinho, Avenida Amazonas, 2218, 30180-00, Belo Horizonte, MG, Brazil.
BMC Vet Res. 2015 Apr 11;11:92. doi: 10.1186/s12917-015-0397-6.
The main control strategy for visceral leishmaniasis in Brazil has been based on the elimination of seropositive dogs, although this is not widely accepted. In this context, the use of a long-lasting protective vaccine against canine visceral leishmaniasis (CVL) has been highly expected. The aim of this work was to determine the timeline kinetics of the cytokine microenvironment derived from circulating leukocytes as supportive immunological biomarkers triggered by Leishmune® vaccine. Cross-sectional kinetic analysis of cellular immunity cytokines was carried out at three times (1, 6 and 12 months) after primovaccination with Leishmune®. In vitro short-term whole blood cultures were stimulated with Leishmania infantum soluble antigen (SLAg). The secreted cytokine signatures and their major sources were determined.
At six months after vaccination, Leishmune® induced an increase in IL-8, IFN-γ, IL-17a and TNF-α levels and a decrease in IL-10. Cytokine signature analysis revealed a shift in the microenvironment towards a pro-inflammatory profile mediated by IL-8 and IFN-γ. Both, CD4(+) (↑TNF-α(+) and ↑IFN-γ (+)) and CD8(+) (↑IL-17a and ↓IL-4) T-cells contributed to the acquired immune responses observed after stimulation with SLAg.
The changes observed in the cytokine profile suggested that Leishmune® was able to induce an effective response at six months after primovaccination. After one year, it returned to baseline suggesting the need of additional boosting.
巴西内脏利什曼病的主要控制策略一直基于消灭血清反应阳性犬，尽管这一策略并未被广泛接受。在此背景下，人们一直高度期待使用一种长效保护性疫苗来预防犬内脏利什曼病（CVL）。这项工作的目的是确定由利什曼疫苗（Leishmune®）触发的循环白细胞衍生细胞因子微环境的时间动力学，作为支持性免疫生物标志物。在用利什曼疫苗（Leishmune®）进行初次接种后的三个时间点（1、6和12个月）进行了细胞免疫细胞因子的横断面动力学分析。用婴儿利什曼原虫可溶性抗原（SLAg）刺激体外短期全血培养物。确定了分泌的细胞因子特征及其主要来源。
接种疫苗六个月后，利什曼疫苗（Leishmune®）诱导白细胞介素-8（IL-8）、干扰素-γ（IFN-γ）、白细胞介素-17a（IL-17a）和肿瘤坏死因子-α（TNF-α）水平升高，白细胞介素-10（IL-10）水平降低。细胞因子特征分析显示，微环境向由IL-8和IFN-γ介导的促炎谱转变。CD4(+)（TNF-α(+)升高和IFN-γ(+)升高）和CD8(+)（IL-17a升高和IL-4降低）T细胞均促成了用SLAg刺激后观察到的获得性免疫反应。
细胞因子谱中观察到的变化表明，利什曼疫苗（Leishmune®）在初次接种六个月后能够诱导有效反应。一年后，其恢复到基线水平，这表明需要额外加强免疫。
