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比较不同蛋白片段的间日疟原虫红细胞内期蛋白 2b 对总免疫球蛋白 G 抗体的反应。

Comparison of total immunoglobulin G antibody responses to different protein fragments of Plasmodium vivax Reticulocyte binding protein 2b.

机构信息

The Walter and Eliza Hall Institute of Medical Research, 3052, Parkville, Australia.

Department of Medical Biology, The University of Melbourne, 3052, Parkville, Australia.

出版信息

Malar J. 2022 Mar 4;21(1):71. doi: 10.1186/s12936-022-04085-x.

Abstract

BACKGROUND

Plasmodium vivax is emerging as the dominant and prevalent species causing malaria in near-elimination settings outside of Africa. Hypnozoites, the dormant liver stage parasite of P. vivax, are undetectable to any currently available diagnostic test, yet are a major reservoir for transmission. Advances have been made to harness the naturally acquired immune response to identify recent exposure to P. vivax blood-stage parasites and, therefore, infer the presence of hypnozoites. This in-development diagnostic is currently able to detect infections within the last 9-months with 80% sensitivity and 80% specificity. Further work is required to optimize protein expression and protein constructs used for antibody detection.

METHODS

The antibody response against the top performing predictor of recent infection, P. vivax reticulocyte binding protein 2b (PvRBP2b), was tested against multiple fragments of different sizes and from different expression systems. The IgG induced against the recombinant PvRBP2b fragments in P. vivax infected individuals was measured at the time of infection and in a year-long observational cohort; both conducted in Thailand.

RESULTS

The antibody responses to some but not all different sized fragments of PvRBP2b protein are highly correlated with each other, significantly higher 1-week post-P. vivax infection, and show potential for use as predictors of recent P. vivax infection.

CONCLUSIONS

To achieve P. vivax elimination goals, novel diagnostics are required to aid in detection of hidden parasite reservoirs. PvRBP2b was previously shown to be the top candidate for single-antigen classification of recent P. vivax exposure and here, it is concluded that several alternative recombinant PvRBP2b fragments can achieve equal sensitivity and specificity at predicting recent P. vivax exposure.

摘要

背景

间日疟原虫(Plasmodium vivax)正在成为非洲以外消除疟疾地区主要和流行的疟原虫物种。间日疟原虫的休眠肝期寄生虫——休眠子,无法被任何现有的诊断检测方法检测到,但却是主要的传播来源。人们已经取得了进展,可以利用自然获得的免疫反应来识别最近是否接触过间日疟原虫的血期寄生虫,从而推断出休眠子的存在。这种正在开发的诊断方法目前能够在过去 9 个月内检测到 80%的敏感性和 80%的特异性感染。还需要进一步的工作来优化用于抗体检测的蛋白表达和蛋白构建。

方法

针对近期感染最强预测因子——间日疟原虫网状红细胞结合蛋白 2b(PvRBP2b)的抗体反应,对来自不同大小和不同表达系统的多个片段进行了测试。在感染期间和为期一年的观察队列中,对感染间日疟原虫的个体中针对重组 PvRBP2b 片段产生的 IgG 进行了测量,这两个队列都是在泰国进行的。

结果

PvRBP2b 蛋白的一些但不是所有不同大小片段的抗体反应彼此高度相关,在感染间日疟原虫后 1 周显著升高,并显示出作为近期间日疟原虫感染预测因子的潜力。

结论

为了实现消除间日疟原虫的目标,需要新的诊断方法来帮助检测隐藏的寄生虫库。PvRBP2b 之前被证明是用于分类近期间日疟原虫感染的单一抗原的最佳候选物,而在这里,我们得出结论,几个替代的重组 PvRBP2b 片段可以在预测近期间日疟原虫感染方面达到相同的敏感性和特异性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba69/8896302/18bcdfcd9a26/12936_2022_4085_Fig1_HTML.jpg

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