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马来布鲁线虫海藻糖-6-磷酸磷酸酶重组蛋白与人体班氏丝虫免疫血清发生交叉反应,并在小鼠体内产生强大的保护效果。

Recombinant trehalose-6-phosphate phosphatase of Brugia malayi cross-reacts with human Wuchereria bancrofti immune sera and engenders a robust protective outcome in mice.

机构信息

Division of Parasitology, Central Drug Research Institute, A unit of Council of Scientific and Industrial Research, Lucknow-226001, UP, India.

出版信息

Microbes Infect. 2012 Nov;14(14):1330-9. doi: 10.1016/j.micinf.2012.08.006. Epub 2012 Aug 30.

DOI:10.1016/j.micinf.2012.08.006
PMID:22981601
Abstract

Trehalose-6-phosphate phosphatase of Brugia malayi (Bm-TPP) represents an attractive vaccine candidate because it is present in all the major life stages of parasite, but is absent in mammals. We have previously cloned, purified and biochemically characterized Bm-TPP. In the present study, we investigated the cross-reactivity of recombinant Bm-TPP (r-Bm-TPP) with the sera of human bancroftian patients belonging to different disease categories. In silico study using bioinformatics tool demonstrated that Bm-TPP is highly immunogenic in nature. BALB/c mice administered with r-Bm-TPP alone or in combination with Freund's complete adjuvant (FCA) generated a strong IgG response. Further investigations on the antibody isotypes showed generation of a mixed T helper cell response which was marginally biased towards Th1 phenotype. r-Bm-TPP with or without adjuvant lead to significantly increased accumulation of CD4+ and CD8+ T cells in the spleen of infected mice and increased the activation of peritoneal macrophages. Additionally, r-Bm-TPP enhanced the production of both proinflammatory (IL-2, IFN-γ) and anti-inflammatory (IL-4, IL-10) cytokines and mice immunized with r-Bm-TPP alone or in combination with FCA showed 54.5% and 67% protection respectively against B. malayi infective larvae challenge. Taken together, our findings suggest that Bm-TPP is protective in nature and might be a potential candidate for development of vaccine against lymphatic filarial infections.

摘要

班氏丝虫(Brugia malayi)海藻糖-6-磷酸磷酸酶(Bm-TPP)作为一种有吸引力的疫苗候选物,因为它存在于寄生虫的所有主要生命阶段,但在哺乳动物中不存在。我们之前已经克隆、纯化和生化表征了 Bm-TPP。在本研究中,我们研究了重组 Bm-TPP(r-Bm-TPP)与来自不同疾病类别的人类班氏丝虫病患者血清的交叉反应性。使用生物信息学工具的计算机研究表明,Bm-TPP 在本质上具有高度的免疫原性。单独给予 r-Bm-TPP 或与福氏完全佐剂(FCA)联合给予 BALB/c 小鼠,可产生强烈的 IgG 反应。对抗体同种型的进一步研究表明,产生了混合的辅助性 T 细胞反应,其偏向 Th1 表型的程度略有偏差。单独使用 r-Bm-TPP 或与佐剂一起使用,可导致感染小鼠脾脏中 CD4+和 CD8+T 细胞的积聚显著增加,并增加腹腔巨噬细胞的激活。此外,r-Bm-TPP 增强了促炎(IL-2、IFN-γ)和抗炎(IL-4、IL-10)细胞因子的产生,单独用 r-Bm-TPP 免疫或与 FCA 联合免疫的小鼠对 B. malayi 感染性幼虫的攻击分别显示出 54.5%和 67%的保护作用。综上所述,我们的研究结果表明,Bm-TPP 具有保护作用,可能是开发淋巴丝虫病疫苗的潜在候选物。

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