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评估间日疟原虫 siap2 基因座的遗传多样性:一种有希望的有效疟疾疫苗候选者?

Evaluating the genetic diversity of the Plasmodium vivax siap2 locus: A promising candidate for an effective malaria vaccine?

机构信息

School of Biological Sciences, Grupo de Estudios en Genética y Biología Molecular (GEBIMOL), Universidad Pedagógica y Tecnológica de Colombia - UPTC, Tunja, Boyacá, Colombia.

Grupo de Investigaciones Microbiológicas y Biomédicas de Córdoba (GIMBIC), School of Health Sciences, Universidad de Córdoba, Montería, Córdoba, Colombia.

出版信息

Acta Trop. 2024 Mar;251:107111. doi: 10.1016/j.actatropica.2023.107111. Epub 2023 Dec 25.

Abstract

Malaria is the deadliest parasitic disease in the world. Traditional control measures have become less effective; hence, there is a need to explore alternative strategies, such as antimalarial vaccines. However, designing an anti-Plasmodium vivax vaccine is considered a challenge due to the complex parasite biology and the antigens' high genetic diversity. Recently, the sporozoite invasion-associated protein 2 (SIAP2) has been suggested as a potential antigen to be considered in vaccine design due to its significance during hepatocyte invasion. However, its use may be limited by the incomplete understanding of gene/protein diversity. Here, the genetic diversity of pvsiap2 using P. vivax DNA samples from Colombia was assessed. Through PCR amplification and sequencing, we compared the Colombian sequences with available worldwide sequences, revealing that pvsiap2 displays low genetic diversity. Molecular evolutionary analyses showed that pvsiap2 appears to be influenced by directional selection. Moreover, the haplotypes found differ by a few mutational steps and several of them were shared between different geographical areas. On the other hand, several conserved regions within PvSIAP2 were predicted as potential B-cell or T-cell epitopes. Considering these characteristics and its role in hepatocyte invasion, the PvSIAP2 protein emerges as a promising antigen to be considered in a multi-antigen-multi-stage (multivalent) fully effective vaccine against P. vivax malaria.

摘要

疟疾是世界上最致命的寄生虫病。传统的控制措施已经变得不那么有效;因此,有必要探索替代策略,如抗疟疫苗。然而,由于寄生虫生物学的复杂性和抗原的高度遗传多样性,设计抗间日疟原虫疫苗被认为是一个挑战。最近,裂殖子入侵相关蛋白 2(SIAP2)被认为是疫苗设计中一个有潜力的候选抗原,因为它在肝细胞入侵过程中具有重要意义。然而,由于对基因/蛋白质多样性的不完全了解,其应用可能受到限制。在这里,使用来自哥伦比亚的间日疟原虫 DNA 样本评估了 pvsiap2 的遗传多样性。通过 PCR 扩增和测序,我们将哥伦比亚的序列与全球可用序列进行了比较,结果表明 pvsiap2 显示出较低的遗传多样性。分子进化分析表明,pvsiap2 似乎受到定向选择的影响。此外,发现的单倍型仅相差几个突变步骤,其中一些在不同地理区域之间共享。另一方面,在 PvSIAP2 内预测了几个保守区域,作为潜在的 B 细胞或 T 细胞表位。考虑到这些特征及其在肝细胞入侵中的作用,PvSIAP2 蛋白作为一种有前途的抗原,有望被纳入针对间日疟原虫疟疾的多抗原-多阶段(多价)完全有效疫苗中。

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