Global diversity of the gene encoding the Pfs25 protein-a Plasmodium falciparum transmission-blocking vaccine candidate.
Global diversity of the gene encoding the Pfs25 protein-a Plasmodium falciparum transmission-blocking vaccine candidate.
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DOI：
10.1186/s13071-021-05078-6
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发表时间：
2021-11-08
影响因子：
3.2
通讯作者：
Pattaradilokrat S
中科院分区：
文献类型：
--
作者：
Sookpongthai P;Utayopas K;Sitthiyotha T;Pengsakul T;Kaewthamasorn M;Wangkanont K;Harnyuttanakorn P;Chunsrivirot S;Pattaradilokrat S
针对疟疾寄生虫恶性疟原虫性阶段的疫苗对于控制疟疾和消除抗药性寄生虫的传播是必不可少的。Pfs 25是恶性疟原虫性期的表面抗原，是传播阻断疫苗开发的主要候选者。虽然临床试验已经报道基于Pfs 25的疫苗在诱导传播阻断抗体方面是安全和有效的，但Pfs 25在疟疾流行人群中的遗传多样性程度很少被研究。因此，本研究旨在研究恶性疟原虫Pfs 25基因的全球多样性。建立了包含307个恶性疟原虫Pfs 25基因序列的数据库。通过群体遗传学分析，对Pfs 25基因的单倍型和核苷酸多样性进行了评估，分析了Pfs 25基因在不同地理群体中的单倍型分布模式，并构建了单倍型网络。进行中性测试以确定自然选择的证据。构建了Pfs 25单倍型的同源模型，进行分子动力学（MD），并分析了二级结构的灵活性和百分比。恶性疟原虫Pfs 25基因有11种独特的单倍型。其中，H1和H2是主要的单倍型，分别占人口的70%和22%，在亚洲占主导地位，而只有H1在非洲，中美洲和南美洲占主导地位。其他单倍型是罕见的和区域特异性，导致在不同的地理种群的独特的分布模式。Pfs 25的多样性来源于位于表皮生长因子（EGF）样结构域和锚结构域的10个单核苷酸多态性（SNP）位点。其中，392位的SNP（GGA/GCA）导致氨基酸取代131（Gly/Ala），定义了两种主要的单倍型。分子动力学结果表明H1和H2变体的结构相对相似。Pfs 25中有限的多态性可能是由于负选择。该研究成功地建立了Pfs 25序列数据库，该数据库可以成为监测疫苗效力、设计检测疟疾携带者的检测方法以及进行恶性疟原虫流行病学研究的重要工具。H1和H2两种主要单倍型及其保守结构的发现表明，目前基于Pfs 25的疫苗可用于全球疟疾控制。在线版本包含补充材料，可通过10.1186/s13071-021-05078-6获得。
Vaccines against the sexual stages of the malarial parasite Plasmodium falciparum are indispensable for controlling malaria and abrogating the spread of drug-resistant parasites. Pfs25, a surface antigen of the sexual stage of P. falciparum, is a leading candidate for transmission-blocking vaccine development. While clinical trials have reported that Pfs25-based vaccines are safe and effective in inducing transmission-blocking antibodies, the extent of the genetic diversity of Pfs25 in malaria endemic populations has rarely been studied. Thus, this study aimed to investigate the global diversity of Pfs25 in P. falciparum populations. A database of 307 Pfs25 sequences of P. falciparum was established. Population genetic analyses were performed to evaluate haplotype and nucleotide diversity, analyze haplotypic distribution patterns of Pfs25 in different geographical populations, and construct a haplotype network. Neutrality tests were conducted to determine evidence of natural selection. Homology models of the Pfs25 haplotypes were constructed, subjected to molecular dynamics (MD), and analyzed in terms of flexibility and percentages of secondary structures. The Pfs25 gene of P. falciparum was found to have 11 unique haplotypes. Of these, haplotype 1 (H1) and H2, the major haplotypes, represented 70% and 22% of the population, respectively, and were dominant in Asia, whereas only H1 was dominant in Africa, Central America, and South America. Other haplotypes were rare and region-specific, resulting in unique distribution patterns in different geographical populations. The diversity in Pfs25 originated from ten single-nucleotide polymorphism (SNP) loci located in the epidermal growth factor (EGF)-like domains and anchor domain. Of these, an SNP at position 392 (GGA/GCA), resulting in amino acid substitution 131 (Gly/Ala), defined the two major haplotypes. The MD results showed that the structures of H1 and H2 variants were relatively similar. Limited polymorphism in Pfs25 could likely be due to negative selection. The study successfully established a Pfs25 sequence database that can become an essential tool for monitoring vaccine efficacy, designing assays for detecting malaria carriers, and conducting epidemiological studies of P. falciparum. The discovery of the two major haplotypes, H1 and H2, and their conserved structures suggests that the current Pfs25-based vaccines could be used globally for malaria control. The online version contains supplementary material available at 10.1186/s13071-021-05078-6.
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影响因子：
5.5
作者：
Goetz, Andreas W.;Williamson, Mark J.;Xu, Dong;Poole, Duncan;Le Grand, Scott;Walker, Ross C.
通讯作者：
Walker, Ross C.
DOI：
10.1084/jem.174.5.1203
发表时间：
1991-11-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Barr PJ;Green KM;Gibson HL;Bathurst IC;Quakyi IA;Kaslow DC
通讯作者：
Kaslow DC
影响因子：
7.3
作者：
Brod, Florian;Miura, Kazutoyo;Biswas, Sumi
通讯作者：
Biswas, Sumi
DOI：
10.1016/s0169-4758(96)10077-6
发表时间：
1997-01-01
期刊：
PARASITOLOGY TODAY
影响因子：
--
作者：
Conway, DJ
通讯作者：
Conway, DJ
DOI：
10.4269/ajtmh.1992.46.711
发表时间：
1992-06-01
影响因子：
3.3
作者：
GRAVES, PM;DOUBROVSKY, A;BATTISTUTTA, D
通讯作者：
BATTISTUTTA, D