Population, genetic, and antigenic diversity of the apicomplexan Eimeria tenella and their relevance to vaccine development

Population, genetic, and antigenic diversity of the apicomplexan Eimeria tenella and their relevance to vaccine development
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DOI:
10.1073/pnas.1506468112
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发表时间:
2015-09-22
影响因子:
11.1
通讯作者:
Tomley, Fiona M.
Tomley, Fiona M.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Blake, Damer P.;Clark, Emily L.;Tomley, Fiona M.

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顶复门包括人类和动物的严重病原体。了解这些原生动物寄生虫的分布和种群结构对于解释疾病流行病学和制定可持续控制措施至关重要。预测亚单位疫苗在田间人群中可能的有效性和寿命依赖于对相关预先存在的抗原多样性、人群结构、遗传上不同的菌株共感染的可能性以及交叉受精的效率的了解。所有这四个因素已被调查的疟原虫种寄生虫,揭示克隆和panmictic人口结构异常多态性与免疫保护性抗原,如顶膜抗原1(AMA1)。对于球虫弓形虫只有基因组多样性和人口结构已被深入定义到目前为止,密切相关的艾美耳球虫物种,所有四个变量目前尚不清楚。使用柔嫩艾美耳球虫,肠道疾病球虫病的主要原因,这对鸡的生产力和福利产生了深远的影响,我们确定了人口结构,基因型分布,和交叉受精的可能性在共感染,也调查了自然发生的抗原多样性的程度为E。tenella AMA1同源物使用全基因组Sequenom基于SNP的单体型分析,靶向测序和单细胞基因分型,我们表明,在这种球虫中,EtAMA1的功能似乎超过了免疫逃避。这一结果与疟原虫中的情况形成直接对比,并且很可能是由最终宿主中的直接和急性球虫生命周期的生物学所支持的。
The phylum Apicomplexa includes serious pathogens of humans and animals. Understanding the distribution and population structure of these protozoan parasites is of fundamental importance to explain disease epidemiology and develop sustainable controls. Predicting the likely efficacy and longevity of subunit vaccines in field populations relies on knowledge of relevant preexisting antigenic diversity, population structure, the likelihood of coinfection by genetically distinct strains, and the efficiency of cross-fertilization. All four of these factors have been investigated for Plasmodium species parasites, revealing both clonal and panmictic population structures with exceptional polymorphism associated with immunoprotective antigens such as apical membrane antigen 1 (AMA1). For the coccidian Toxoplasma gondii only genomic diversity and population structure have been defined in depth so far; for the closely related Eimeria species, all four variables are currently unknown. Using Eimeria tenella, a major cause of the enteric disease coccidiosis, which exerts a profound effect on chicken productivity and welfare, we determined population structure, genotype distribution, and likelihood of cross-fertilization during coinfection and also investigated the extent of naturally occurring antigenic diversity for the E. tenella AMA1 homolog. Using genome-wide Sequenom SNP-based haplotyping, targeted sequencing, and single-cell genotyping, we show that in this coccidian the functionality of EtAMA1 appears to outweigh immune evasion. This result is in direct contrast to the situation in Plasmodium and most likely is underpinned by the biology of the direct and acute coccidian life cycle in the definitive host.