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用感染性曼氏血吸虫重组海藻糖-6-磷酸磷酸酶免疫坎氏梳趾鼠可显著抵抗同源攻毒感染。

Immunization of Mastomys coucha with Brugia malayi recombinant trehalose-6-phosphate phosphatase results in significant protection against homologous challenge infection.

机构信息

Division of Parasitology, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India.

出版信息

PLoS One. 2013 Aug 28;8(8):e72585. doi: 10.1371/journal.pone.0072585. eCollection 2013.

Abstract

Development of a vaccine to prevent or reduce parasite development in lymphatic filariasis would be a complementary approach to existing chemotherapeutic tools. Trehalose-6-phosphate phosphatase of Brugia malayi (Bm-TPP) represents an attractive vaccine target due to its absence in mammals, prevalence in the major life stages of the parasite and immunoreactivity with human bancroftian antibodies, especially from endemic normal subjects. We have recently reported on the cloning, expression, purification and biochemical characterization of this vital enzyme of B. malayi. In the present study, immunoprophylactic evaluation of Bm-TPP was carried out against B. malayi larval challenge in a susceptible host Mastomys coucha and the protective ability of the recombinant protein was evaluated by observing the adverse effects on microfilarial density and adult worm establishment. Immunization caused 78.4% decrease in microfilaremia and 71.04% reduction in the adult worm establishment along with sterilization of 70.06% of the recovered live females. The recombinant protein elicited a mixed Th1/Th2 type of protective immune response as evidenced by the generation of both pro- and anti-inflammatory cytokines IL-2, IFN-γ, TNF-α, IL-4 and an increased production of antibody isotypes IgG1, IgG2a, IgG2b and IgA. Thus immunization with Bm-TPP conferred considerable protection against B. malayi establishment by engendering a long-lasting effective immune response and therefore emerges as a potential vaccine candidate against lymphatic filariasis (LF).

摘要

开发一种预防或减少淋巴丝虫病寄生虫发育的疫苗将是对现有化学治疗工具的补充方法。来源于班氏吴策线虫(Brugia malayi)的海藻糖-6-磷酸磷酸酶(Bm-TPP)因其在哺乳动物中不存在、在寄生虫的主要生命阶段普遍存在以及与人类班氏丝虫抗体(尤其是来自流行地区的正常个体)发生免疫反应而成为有吸引力的疫苗靶标。我们最近报道了该酶在班氏吴策线虫中的克隆、表达、纯化和生化特征。在本研究中,针对易感宿主 Mastomys coucha 的班氏吴策线虫幼虫挑战,对 Bm-TPP 进行了免疫预防评估,并通过观察对微丝蚴密度和成虫建立的不利影响来评估重组蛋白的保护能力。免疫接种导致微丝蚴血症减少 78.4%,成虫建立减少 71.04%,同时恢复的活雌性中有 70.06%被绝育。重组蛋白引发了 Th1/Th2 混合型保护性免疫反应,这表现在产生了促炎和抗炎细胞因子 IL-2、IFN-γ、TNF-α、IL-4,以及抗体同种型 IgG1、IgG2a、IgG2b 和 IgA 的产生增加。因此,Bm-TPP 免疫接种通过产生持久有效的免疫反应,对班氏吴策线虫的建立提供了相当大的保护,因此成为淋巴丝虫病(LF)的潜在疫苗候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2ad/3755969/cbc6d6519d54/pone.0072585.g001.jpg

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