Extent of polymorphism and selection pressure on the Trypanosoma cruzi vaccine candidate antigen Tc24.
Extent of polymorphism and selection pressure on the Trypanosoma cruzi vaccine candidate antigen Tc24.
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DOI：
10.1111/eva.13068
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发表时间：
2020-12
影响因子：
4.1
通讯作者：
Dumonteil E
中科院分区：
文献类型：
--
作者：
Arnal A;Villanueva-Lizama L;Teh-Poot C;Herrera C;Dumonteil E
由原生动物寄生虫克氏锥虫引起的恰加斯病是美洲的一个主要公共卫生问题，现有药物具有严重的局限性。在这种情况下，疫苗将是一种有吸引力的疾病控制替代品。研制有效疫苗的难点之一在于T.克鲁兹在这项研究中，我们评估了领先的候选疫苗Tc 24在多种寄生虫菌株中的序列多样性水平。我们量化了T. cruzi离散分型单位（DTU），以及这种潜在的多态性是如何通过不同的选择压力结构。我们观察到一个低水平的Tc 24蛋白的多态性，弱相关的寄生虫DTUs，但不与菌株的地理来源。特别是，Tc 24处于强大的纯化选择压力下，预测的CD 8 + T细胞表位大多是保守的。Tc 24强保守性可能与结构/功能限制有关，以保护EF手结构域及其钙结合环，Tc 24可能对寄生虫适应性很重要。总之，这些结果表明，基于Tc 24的疫苗可能对美洲大陆各种各样的寄生虫株有效，这种候选疫苗的进一步开发应该是一个高度优先事项。
Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is a major public health problem in the Americas, and existing drugs have severe limitations. In this context, a vaccine would be an attractive alternative for disease control. One of the difficulties in developing an effective vaccine lies in the high genetic diversity of T. cruzi. In this study, we evaluated the level of sequence diversity of the leading vaccine candidate Tc24 in multiple parasite strains. We quantified its level of polymorphism within and between T. cruzi discrete typing units (DTUs) and how this potential polymorphism is structured by different selective pressures. We observed a low level of polymorphism of Tc24 protein, weakly associated with parasite DTUs, but not with the geographic origin of the strains. In particular, Tc24 was under strong purifying selection pressure and predicted CD8+ T‐cell epitopes were mostly conserved. Tc24 strong conservation may be associated with structural/functional constrains to preserve EF hand domains and their calcium‐binding loops, and Tc24 is likely important for the parasite fitness. Together, these results show that a vaccine based on Tc24 is likely to be effective against a wide diversity of parasite strains across the American continent, and further development of this vaccine candidate should be a high priority.
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影响因子：
158.5
作者：
Bern, Caryn
通讯作者：
Bern, Caryn
影响因子：
6.4
作者：
DA Silva, AC;Espinoza, AG;Minoprio, P
通讯作者：
Minoprio, P
影响因子：
5.5
作者：
Haolla, Filipe A.;Claser, Carla;Rodrigues, Mauricio M.
通讯作者：
Rodrigues, Mauricio M.
DOI：
10.1098/rspb.2016.2562
发表时间：
2017-03-29
期刊：
Proceedings. Biological sciences
影响因子：
--
作者：
Kennedy DA;Read AF
通讯作者：
Read AF
影响因子：
3
作者：
Doytchinova IA;Guan P;Flower DR
通讯作者：
Flower DR