Animal Disease Research Unit, Agricultural Research Service, United States Department of Agriculture, Pullman, WA 99164-6630, USA.
Vet Parasitol. 2011 Aug 4;180(1-2):109-25. doi: 10.1016/j.vetpar.2011.05.032. Epub 2011 May 27.
The Babesia bovis and B. bigemina apicomplexan protozoa in conjunction with the rickettsia Anaplasma marginale are intraerythrocytic pathogens that are responsible for the most prevalent and costly tick borne diseases (TBD's) of cattle worldwide. These organisms are historically associated as they can cause clinically related hemolytic diseases in cattle, are all transmitted by Rhiphicephallus (Boophilus) ticks, and share an uncanny ability to evade the immune systems of the vertebrate hosts, causing persistent disease. In addition, acute babesiosis and anaplasmosis can be prevented quite effectively by combining tick control and vaccination with living attenuated organisms. However these methods of control have numerous limitations and improved approaches are needed. Importantly, immunizations of cattle with inactivated experimental Babesia and Anaplasma vaccines can elicit variable degrees of protection, indicating the feasibility for the development of inactivated or subunit vaccines. A new research toolbox that includes full genome sequencing combined with the improved ability to genetically modify the organisms is enhancing our understanding of their biology. An emerging paradigm is the use of recently developed Babesia and Anaplasma transfection methods for functional gene characterizations and for vaccine development. Promising recently identified subunit vaccine candidates are also emerging, including babesial proteases, putative rhoptry, microneme, and sexual stage antigens, as well as subdominant, conserved, A. marginale outer membrane major surface proteins. However, significant knowledge gaps on the role of key parasite molecules involved in cell invasion, adhesion, asexual and sexual reproduction, tick transmission, and evasion of the immune system, remain. A better understanding of the biology of these organisms and the protective immune responses will positively contribute toward the goal of developing improved immunological and pharmacological interventions against these elusive pathogens that are responsible for the most devastating TBD's of cattle. Importantly, the currently available research toolbox provides basic research instruments for helping close current knowledge gaps which will aid the design and production of effective vaccines and alternative pharmacological interventions.
巴贝斯虫属和双芽巴贝斯虫属原生动物与立克次体属边缘无浆体共同构成了红细胞内寄生虫，它们是造成全球范围内最普遍和最昂贵的蜱传疾病（TBD）的罪魁祸首。这些生物体在历史上是相关的，因为它们可以在牛中引起临床相关的溶血性疾病，都是由革蜱（Boophilus）传播的，并且都具有逃避脊椎动物宿主免疫系统的不可思议的能力，导致持续性疾病。此外，通过将蜱控制和活减毒生物疫苗接种相结合，急性巴贝斯虫病和无浆体病可以得到相当有效的预防。然而，这些控制方法存在许多局限性，需要改进方法。重要的是，用灭活实验性巴贝斯虫和无浆体疫苗对牛进行免疫接种可以引起不同程度的保护，这表明开发灭活或亚单位疫苗是可行的。一个新的研究工具箱，包括全基因组测序和遗传修饰生物体能力的提高，正在增强我们对其生物学的理解。一个新兴的范例是利用最近开发的巴贝斯虫和无浆体转染方法进行功能基因特征分析和疫苗开发。最近出现的有前途的亚单位疫苗候选物也在出现，包括巴贝斯虫蛋白酶、假定的泡状蛋白、微线体蛋白和有性阶段抗原，以及亚显性、保守的、边缘无浆体外膜主要表面蛋白。然而，在参与细胞入侵、黏附、无性和有性繁殖、蜱传播和逃避免疫系统的关键寄生虫分子的作用方面，仍存在显著的知识差距。更好地了解这些生物体的生物学和保护性免疫反应将有助于开发针对这些逃避性病原体的改进免疫和药理学干预措施，这些病原体是造成牛最具破坏性的 TBD 的罪魁祸首。重要的是，目前可用的研究工具箱为缩小当前的知识差距提供了基础研究工具，这将有助于设计和生产有效的疫苗和替代药理学干预措施。
