Multistrain genome analysis identifies candidate vaccine antigens of Anaplasma marginale.

Multistrain genome analysis identifies candidate vaccine antigens of Anaplasma marginale.
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DOI:
10.1016/j.vaccine.2011.04.131
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发表时间:
2011-07-12
期刊:
影响因子:
5.5
通讯作者:
Barbet, Anthony F.
Barbet, Anthony F.
中科院分区:
医学3区
文献类型:
--
作者:
Dark, Michael J.;Al-Khedery, Basima;Barbet, Anthony F.

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家畜无形体病是世界范围内动物健康和生产的障碍,特别是在非洲,亚洲和南美洲的发展中国家。针对致病微生物边缘无浆体的疫苗已经开发并上市;然而,由于异源菌株引起的突破性感染以及活疫苗菌株本身诱发疾病的风险,这些疫苗尚未广泛使用。最近,分子研究使我们能够在理解突破性感染的原因和确定新的疫苗靶点方面取得进展。A. marginale具有MSP 2和MSP 3外膜蛋白的抗原变异系统,所述MSP 2和MSP 3外膜蛋白是pfam 01617基因超家族的成员。在这项研究中,我们使用高通量基因组测序来确定10个美国A. marginale和相关的活疫苗株A。边缘亚种中央亚种。这些比较包括导致抗原变异的假基因和其他超家族编码的外膜蛋白。此外,我们还研究了以前提出的作为疫苗候选物的其他蛋白质的保守性。这些数据表明,在A.边缘亚种centrale相比,所有美国。边缘菌株我们定义了一个目录的19个保守的候选疫苗抗原,可能适合于开发的多组分重组疫苗。所描述的方法是快速的,并且可能适用于重复序列构成其基因组的实质部分的其他原核生物。
Anaplasmosis in domestic livestock is an impediment to animal health and production worldwide, especially in developing countries in Africa, Asia, and South America. Vaccines have been developed and marketed against the causative organism, Anaplasma marginale; however, these have not been widely used because of breakthrough infections caused by heterologous strains and because of the risk of disease induced by live vaccine strains themselves. Recently, molecular studies have enabled progress to be made in understanding the causes for breakthrough infections and in defining new vaccine targets. A. marginale has a system for antigenic variation of the MSP2 and MSP3 outer membrane proteins which are members of the pfam01617 gene superfamily. In this study, we used high throughput genome sequencing to define conservation of different superfamily members in ten U.S. strains of A. marginale and also in the related live vaccine strain A. marginale subspecies centrale. The comparisons included the pseudogenes that contribute to antigenic variation and other superfamily-encoded outer membrane proteins. Additionally, we examined conservation of other proteins proposed previously as vaccine candidates. These data showed significantly increased numbers of SNPs in A. marginale subspecies centrale when compared to all U.S. A. marginale strains. We defined a catalog of 19 conserved candidate vaccine antigens that may be suitable for development of a multi-component recombinant vaccine. The methods described are rapid and may be suitable for other prokaryotes where repeats comprise a substantial portion of their genomes.
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