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Genetic polymorphisms in the glutamate-rich protein of Plasmodium falciparum field isolates from a malaria-endemic area of Brazil

机译:巴西疟原虫区疟原虫场分离株谷氨酸富含谷氨酸富含蛋白质的遗传多态性

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The genetic diversity displayed by Plasmodium falciparum , the most deadly Plasmodium species, is a significant obstacle for effective malaria vaccine development. In this study, we identified genetic polymorphisms in P. falciparum glutamate-rich protein (GLURP), which is currently being tested in clinical trials as a malaria vaccine candidate, from isolates found circulating in the Brazilian Amazon at variable transmission levels. The study was performed using samples collected in 1993 and 2008 from rural villages situated near Porto Velho, in the state of Rond?nia. DNA was extracted from 126 P. falciparum-positive thick blood smears using the phenol-chloroform method and subjected to a nested polymerase chain reaction protocol with specific primers against two immunodominant regions of GLURP, R0 and R2. Only one R0 fragment and four variants of the R2 fragment were detected. No differences were observed between the two time points with regard to the frequencies of the fragment variants. Mixed infections were uncommon. Our results demonstrate conservation of GLURP-R0 and limited polymorphic variation of GLURP-R2 in P. falciparum isolates from individuals living in Porto Velho. This is an important finding, as genetic polymorphisms in B and T-cell epitopes could have implications for the immunological properties of the antigen.
机译:疟原虫疟原虫,最致命的疟原虫物种展示的遗传多样性是有效疟疾疫苗发育的重要障碍。在这项研究中,我们确定了富含疟原虫的富含谷氨酸谷物(Glurp)的遗传多态性,目前正在在疟疾疫苗候选人中在临床试验中进行测试,从发现在巴西亚马逊处于可变变速器水平的分离物中。该研究是使用1993年和2008年收集的样品从位于罗隆(Rondo)附近的农村村庄,在罗隆的乡村村。使用苯酚 - 氯仿方法从126pp. falciparum阳性厚的血液涂片中提取DNA,并进行嵌套聚合酶链反应方案,其具有针对Glurp,R0和R2的两个免疫肿瘤区域的特异性引物。检测到R2片段的仅一个R0片段和四个变体。在碎片变体的频率方面,在两个时间点之间没有观察到差异。混合感染罕见。我们的结果表明,在Porto Velho的个人中,P. falciparum孤立的Glurp-R2的Glurp-R0和GluRP-R2的有限多态变异。这是一个重要的发现,因为B和T细胞表位的遗传多态性可能对抗原的免疫特性有影响。

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