Ahmed Md Atique, Baruah Pratisthita, Saif Ahmed, Han Jin-Hee, Al-Zharani Mohammed, Wazid Syeda Wasfeea, Alkahtani Saad, Patgiri Saurav J, Al-Eissa Mohammed S, Quan Fu-Shi
ICMR-Regional Medical Research Centre, NE Region, Dibrugarh 786010, Assam, India.
Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, King Khalid University, Abha 61321, Saudi Arabia.
Trop Med Infect Dis. 2023 Jul 26;8(8):380. doi: 10.3390/tropicalmed8080380.
The cell-traversal protein for ookinetes and sporozoites (CelTOS), expressed on the surface of ookinetes and sporozoitesin , is a promising malaria vaccine candidate. CelTOS is essential for parasite invasion into mosquito midgut and human hepatocytes, thereby contributing to malaria transmission and disease pathogenesis. This study explores the genetic diversity, polymorphisms, haplotypes, natural selection, phylogenetic analysis, and epitope prediction in the full-length gene in clinical samples from Sarawak, Malaysian Borneo, and long-term laboratory strains from Peninsular Malaysia and the Philippines. Our analysis revealed a high level of genetic variation in the gene, with a nucleotide diversity of π ~ 0.021, which was skewed towards the 3' end of the gene. This level of diversity is double that observed in and 20 times that observed in from worldwide clinical samples. Tests of natural selection revealed evidence for positive selection within clinical samples. Phylogenetic analysis of the amino acid sequence of revealed the presence of two distinct groups, although no geographical clustering was observed. Epitope prediction analysis identified two potential epitopes (96AQLKATA102 and 124TIKPPRIKED133) using the IEDB server and one epitope (125IKPPRIKED133) by Bcepred server on the C' terminal region of protein. Both the servers predicted a common epitope region of nine amino acid length (IKPPRIKED) peptide, which can be studied in the future as a potential candidate for vaccine development. These findings shed light on the genetic diversity, polymorphism, haplotypes, and natural selection within in clinical samples and provide insights about its future prospects as a potential candidate for malaria vaccine development.
动合子和子孢子的细胞穿越蛋白（CelTOS）在动合子和子孢子表面表达，是一种很有前景的疟疾疫苗候选物。CelTOS对于寄生虫侵入蚊子中肠和人类肝细胞至关重要，从而促进疟疾传播和疾病发病机制。本研究探索了马来西亚婆罗洲砂拉越临床样本以及马来西亚半岛和菲律宾长期实验室菌株中全长基因的遗传多样性、多态性、单倍型、自然选择、系统发育分析和表位预测。我们的分析揭示了该基因高水平的遗传变异，核苷酸多样性π约为0.021，且偏向于基因的3'端。这种多样性水平是全球临床样本中观察到的该基因多样性的两倍，是另一种基因多样性的20倍。自然选择测试揭示了临床样本中存在正选择的证据。对该基因氨基酸序列的系统发育分析显示存在两个不同的组，尽管未观察到地理聚类。表位预测分析使用IEDB服务器确定了两个潜在表位（96AQLKATA102和124TIKPPRIKED133），并通过Bcepred服务器在该蛋白的C端区域确定了一个表位（125IKPPRIKED133）。两个服务器都预测了一个九氨基酸长度（IKPPRIKED）肽的共同表位区域，未来可将其作为疫苗开发的潜在候选物进行研究。这些发现揭示了临床样本中该基因的遗传多样性、多态性、单倍型和自然选择情况，并为其作为疟疾疫苗开发潜在候选物的未来前景提供了见解。
