Genetic variation among Plasmodium vivax isolates adapted to non-human primates and the implication for vaccine development.

Genetic variation among Plasmodium vivax isolates adapted to non-human primates and the implication for vaccine development.
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DOI:
10.4269/ajtmh.2009.80.218
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发表时间:
2009-02
期刊:
The American journal of tropical medicine and hygiene
影响因子:
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通讯作者:
F. Ntumngia;A. McHenry;J. Barnwell;Jennifer L Cole-Tobian;C. King;J. Adams
F. Ntumngia;A. McHenry;J. Barnwell;Jennifer L Cole-Tobian;C. King;J. Adams
中科院分区:
其他
文献类型:
--
作者:
F. Ntumngia;A. McHenry;J. Barnwell;Jennifer L Cole-Tobian;C. King;J. Adams

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间日疟原虫Duffy结合蛋白(DBP)对寄生虫的发育至关重要,因此使该分子成为很好的疫苗候选分子。间日疟原虫疫苗的临床前开发通常涉及在人类身上测试疗效之前使用灵长类模型,但灵长类分离株的特征很差。我们分析了几个用于实验灵长类感染的间日疟原虫分离株的DBP完整基因编码,并将这些序列与正在用于疫苗开发的萨尔瓦多I DBP分离株进行了比较。我们的结果证实,灵长类适应的分离株在遗传上类似于在人类中传播的间日疟原虫,但在假定的保护性抗体的靶标上变异性最大。此外,一些间日疟原虫分离株含有多个遗传上不同的克隆。因此,由于可供体内挑战的间日疟原虫分离株的异质性和多样性,测试DBP疫苗可能会变得复杂。
Plasmodium vivax Duffy binding protein (DBP) is vital for parasite development, thereby making this molecule a good vaccine candidate. Preclinical development of a P. vivax vaccine often involves use of primate models prior to testing efficacy in humans, but primate isolates are poorly characterized. We analyzed the complete gene coding for the DBP in several P. vivax isolates that are used for experimental primate infections and compared these sequences with the Salvador I DBP isolate, which is being used for vaccine development. Our results affirm that primate-adapted isolates are genetically similar to P. vivax circulating in humans, but variability is greatest in the putative target of protective antibodies. In addition, some P. vivax isolates contain multiple genetically different clones. Testing a DBP vaccine may therefore be complicated by heterogeneity and diversity of the P. vivax isolates available for in vivo challenge.