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首页> 美国卫生研究院文献>Elsevier Sponsored Documents >Antibodies to in silico selected GPI-anchored Theileria parva proteins neutralize sporozoite infection in vitro
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Antibodies to in silico selected GPI-anchored Theileria parva proteins neutralize sporozoite infection in vitro

机译：在计算机上选择的GPI锚定的Theileria parva蛋白抗体可在体外中和子孢子感染

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East Coast fever (ECF) caused by Theileria parva kills cattle in East, Central and Southern Africa leading to significant economic losses. Vaccination is used as a control strategy against ECF and is presently dependent on deliberate infection with live sporozoites and simultaneous treatment with a long-acting oxytetracycline. Although effective, this method has serious limitations; the immunity is parasite strain specific and immunized cattle can become life-long asymptomatic carriers of the parasite, posing risk for the spread of the disease. In efforts to develop a subunit vaccine, the role of antibodies in the neutralization of T. parva sporozoites infection of host cells has been investigated and a circumsporozoite protein, p67, is able to induce such neutralizing antibodies. However, the p67 protein only protects a proportion of immunized cattle against T. parva challenge and such protection might be improved by inclusion of additional parasite antigens that neutralize sporozoite infection. In an attempt to identify such antigens, we searched the re-annotated T. parva genome for genes predicted to contain GPI anchor signals, since they are likely to be located on the cell surface, and expressed fragments of six of the selected genes in E. coli. The recombinant proteins were used to raise antisera in mice. Antisera to two proteins, TpMuguga_01g00876 and TpMuguga_01g00939, neutralized sporozoite infectivity to a high degree, while antisera to two additional proteins, TpMuguga_01g00095 and TpMuguga_04g00437, exhibited moderate neutralizing capacity. We conclude that these four antigens are potential vaccine candidates, which should be evaluated further in cattle.
机译：Theileria parva引起的东海岸热（ECF）杀死了东非，中非和南部非洲的牛，导致重大经济损失。接种疫苗被用作对抗ECF的控制策略，目前取决于活子孢子的故意感染以及长效土霉素的同时治疗。尽管有效，但这种方法有严重的局限性。免疫是寄生虫毒株特有的，免疫的牛可以成为该寄生虫的终生无症状携带者，从而构成疾病传播的风险。在开发亚单位疫苗的努力中，已经研究了抗体在中和小球囊虫子孢子感染宿主细胞中的作用，并且环子孢子蛋白p67能够诱导这种中和抗体。但是，p67蛋白仅能保护一部分免疫的牛免受T. parva攻击，并且可以通过加入中和子孢子感染的其他寄生虫抗原来改善这种保护。为了鉴定此类抗原，我们搜索了重新注释的帕氏梭菌基因组，寻找可能包含GPI锚信号的基因，因为它们很可能位于细胞表面，并在E中表达了六个选定基因的片段大肠杆菌重组蛋白用于在小鼠中产生抗血清。对两种蛋白TpMuguga_01g00876和TpMuguga_01g00939的抗血清在很大程度上中和了子孢子的感染性，而对另外两种蛋白TpMuguga_01g00095和TpMuguga_04g00437的抗血清则表现出中等的中和能力。我们得出结论，这四种抗原是潜在的疫苗候选者，应在牛中对其进行进一步评估。

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