In silico identification of Leishmania GP63 protein epitopes to generate a new vaccine antigen against leishmaniasis.

IF 3.4 2区医学 Q1 PARASITOLOGY

PLoS Neglected Tropical Diseases Pub Date : 2025-06-05 eCollection Date: 2025-06-01 DOI:10.1371/journal.pntd.0013137

Mervenur Güvendi, Hüseyin Can, İrem Yavuz, Ahmet Özbilgin, Aysu Değirmenci Döşkaya, Muhammet Karakavuk, Cemal Ün, Adnan Yüksel Gürüz, İsmail Cem Yılmaz, Mayda Gürsel, İhsan Gürsel, Mert Döşkaya

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引用次数: 0

Abstract

Background: The surface of Leishmania spp. presents glycoprotein 63 (GP63), a metalloprotease that acts as one of the parasite's major antigens. A vaccine against leishmaniasis has not yet been developed and stationary phase promastigotes have utmost importance in transmitting Leishmania spp. from phlebotomine sand fly to humans or reservoirs. Therefore, this study aimed to analyze GP63 protein in three different Leishmania spp. to determine new vaccine candidate antigen against leishmaniasis using sequencing data of locally detected Leishmania strains and in silico approaches.

Methodology/principal findings: The GP63 protein sequences of the stationary phase/amastigote form of L. infantum, L. major, and L. tropica were identified and then the gene encoding GP63 protein in Leishmania positive samples (n:59) was amplified and sequenced for variation analysis. According to the results, 4, 6, 19 GP63 variants were found within L. infantum, L. major, and L. tropica isolates, respectively. The most prevalent variants within each species were selected for further analysis using in silico approaches. Accordingly, all selected GP63 proteins were antigenic and the amount of B and T cell epitopes were 23 for L. infantum, 10 for L. major, and 9 for L. tropica. The analysis of each epitope showed that all of them were non-toxic, non-allergen, and soluble but had different antigenicity values. Among these epitopes, EMEDQGSAGSAGS associated with L. major, STHDSGSTTC and AEDILTDEKRDILRK epitopes associated with L. infantum had the highest antigenicity values for B cell, MHC-I, and MHC-II epitopes, respectively. Moreover, conserved epitopes were detected among two or three Leishmania species.

Conclusions/significance: This study detected many epitopes that could be used in vaccine studies and the development of serological diagnostic assays.

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利什曼GP63蛋白表位的计算机鉴定及制备新的利什曼病疫苗抗原。

背景：利什曼原虫表面存在糖蛋白63 (GP63)，这是一种金属蛋白酶，是寄生虫的主要抗原之一。针对利什曼病的疫苗尚未开发，静止期原鞭毛虫在将利什曼原虫从白蛉蛉传播给人类或宿主方面发挥着至关重要的作用。因此，本研究旨在利用当地检测到的利什曼原虫菌株的测序数据和计算机方法，分析三种不同利什曼原虫的GP63蛋白，以确定新的利什曼病疫苗候选抗原。方法/主要发现：鉴定了利什曼原虫（L. infumtum， L. major， L. tropica）固定相/无梭体形态的GP63蛋白序列，扩增了利什曼原虫阳性样本（n:59）的GP63蛋白编码基因，并对其序列进行了变异分析。结果显示，在婴儿乳杆菌、大乳杆菌和热带乳杆菌分离株中分别发现了4、6、19个GP63变异。在每个物种中选择最普遍的变异，使用计算机方法进行进一步分析。因此，所有选择的GP63蛋白都具有抗原性，B和T细胞表位的数量分别为婴儿乳杆菌23个，主要乳杆菌10个，热带乳杆菌9个。每个表位的分析表明，它们都是无毒、无过敏原、可溶的，但具有不同的抗原性值。其中，与乳酸菌相关的EMEDQGSAGSAGS、与乳酸菌相关的STHDSGSTTC和与乳酸菌相关的AEDILTDEKRDILRK表位对B细胞、MHC-I和MHC-II表位的抗原性值最高。此外，在两三个利什曼原虫种中检测到保守的表位。结论/意义：本研究检测到许多抗原表位，可用于疫苗研究和血清学诊断方法的开发。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

PLoS Neglected Tropical Diseases PARASITOLOGY-TROPICAL MEDICINE

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10.50%

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723

期刊介绍： PLOS Neglected Tropical Diseases publishes research devoted to the pathology, epidemiology, prevention, treatment and control of the neglected tropical diseases (NTDs), as well as relevant public policy. The NTDs are defined as a group of poverty-promoting chronic infectious diseases, which primarily occur in rural areas and poor urban areas of low-income and middle-income countries. Their impact on child health and development, pregnancy, and worker productivity, as well as their stigmatizing features limit economic stability. All aspects of these diseases are considered, including: Pathogenesis Clinical features Pharmacology and treatment Diagnosis Epidemiology Vector biology Vaccinology and prevention Demographic, ecological and social determinants Public health and policy aspects (including cost-effectiveness analyses).