Limited genetic and antigenic diversity within parasite isolates used in a live vaccine against Theileria parva.
Limited genetic and antigenic diversity within parasite isolates used in a live vaccine against Theileria parva.
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DOI：
10.1016/j.ijpara.2016.02.007
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发表时间：
2016-07
影响因子：
4
通讯作者：
Pelle R
中科院分区：
文献类型：
--
作者：
Hemmink JD;Weir W;MacHugh ND;Graham SP;Patel E;Paxton E;Shiels B;Toye PG;Morrison WI;Pelle R
基因分型和基因测序显示活的小泰勒虫疫苗的多样性有限。两种疫苗组分在所有基因座上显示出高度相似性。该疫苗几乎不含T区发现的多样性。parva。该疫苗是次优的产生免疫力再次不同的寄生虫菌株。次要基因型组分的存在给质量控制带来困难。使用感染和治疗方案对牛进行疫苗接种以对抗小泰勒虫感染。由于不同寄生虫分离株之间的交叉保护不完全，因此将三种分离株的混合物（称为Muguga混合物）用于疫苗接种。虽然在某些地区对牛进行疫苗接种可提供高水平的保护，但某些动物不能抵抗水牛源性T。parva。需要了解Muguga鸡尾酒疫苗的遗传组成，以了解疫苗接种如何能够保护免受田间挑战，并确定疫苗的潜在局限性。本研究的目的是确定构成Muguga鸡尾酒的寄生虫分离株内的遗传和抗原多样性程度。抗原编码基因座的高通量多基因座测序与使用一组微卫星和小卫星基因座的分型平行进行。前者集中于编码CD 8 + T细胞抗原的基因，据信与保护性免疫有关。结果表明，三个组分的股票的鸡尾酒包含有限的寄生虫基因型多样性，在许多基因/卫星位点检测到的单等位基因，而且，两个组件显示出非常高的相似性水平。因此，该疫苗结合了很少的遗传和抗原多样性中观察到的外地人口的T。parva。在疫苗组分群体中存在低频率（<10%）的等位基因也表明疫苗剂量含量存在变异性的可能性，以及在蜱虫传代过程中等位基因多样性丧失的可能性。结果表明，有余地修改疫苗的内容，以提高其多样性，从而提高其提供广泛保护的潜力。准确量化疫苗组分库存遗传多样性的能力将有助于改进旨在确保疫苗长期效力的质量控制程序。
Genotyping and gene sequencing reveal limited diversity in a live Theileria parva vaccine. Two of the vaccine components show a high level of similarity at all loci. The vaccine contains very little of the diversity found in field T. parva. The vaccine is suboptimal for generating immunity again diverse parasite strains. The presence of minor genotypic components poses difficulties for quality control. An infection and treatment protocol is used to vaccinate cattle against Theileria parva infection. Due to incomplete cross-protection between different parasite isolates, a mixture of three isolates, termed the Muguga cocktail, is used for vaccination. While vaccination of cattle in some regions provides high levels of protection, some animals are not protected against challenge with buffalo-derived T. parva. Knowledge of the genetic composition of the Muguga cocktail vaccine is required to understand how vaccination is able to protect against field challenge and to identify the potential limitations of the vaccine. The aim of the current study was to determine the extent of genetic and antigenic diversity within the parasite isolates that constitute the Muguga cocktail. High throughput multi-locus sequencing of antigen-encoding loci was performed in parallel with typing using a panel of micro- and mini-satellite loci. The former focused on genes encoding CD8+ T cell antigens, believed to be relevant to protective immunity. The results demonstrate that each of the three component stocks of the cocktail contains limited parasite genotypic diversity, with single alleles detected at many gene/satellite loci and, moreover, that two of the components show a very high level of similarity. Thus, the vaccine incorporates very little of the genetic and antigenic diversity observed in field populations of T. parva. The presence of alleles at low frequency (<10%) within vaccine component populations also points to the possibility of variability in the content of vaccine doses and the potential for loss of allelic diversity during tick passage. The results demonstrate that there is scope to modify the content of the vaccine in order to enhance its diversity and thus its potential for providing broad protection. The ability to accurately quantify genetic diversity in vaccine component stocks will facilitate improved quality control procedures designed to ensure the long-term efficacy of the vaccine.