Department of Infectious Diseases and Pathology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611, USA.
Vaccine. 2011 Jul 12;29(31):4923-32. doi: 10.1016/j.vaccine.2011.04.131. Epub 2011 May 17.
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.
家畜的无形体病是全世界动物健康和生产的障碍，尤其是在非洲、亚洲和南美洲的发展中国家。已经开发和销售了针对病原体边缘无形体的疫苗；然而，由于异源菌株引起的突破性感染以及活疫苗株本身引起疾病的风险，这些疫苗并未得到广泛应用。最近，分子研究使人们对突破性感染的原因以及新的疫苗靶标有了更深入的了解。边缘无形体有一种抗原变异系统，其外膜蛋白 MSP2 和 MSP3 是 pfam01617 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定义 10 株美国边缘无形体菌株和相关的活疫苗株边缘无形体亚种 centrale 中不同超家族成员的保守性。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，我们还检查了先前被提议作为疫苗候选物的其他蛋白质的保守性。与所有美国边缘无形体菌株相比，边缘无形体亚种 centrale 中的 SNP 数量显著增加。我们定义了 19 种保守的候选疫苗抗原目录，这些抗原可能适合开发多组分重组疫苗。所描述的方法快速，可能适用于其他重复序列占其基因组很大一部分的原核生物。
