Global diversity of the gene encoding the Pfs25 protein—a Plasmodium falciparum transmission-blocking vaccine candidate

Abstract Background 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 transmissio...

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Autores principales:	Pornpawee Sookpongthai, Korawich Utayopas, Thassanai Sitthiyotha, Theerakamol Pengsakul, Morakot Kaewthamasorn, Kittikhun Wangkanont, Pongchai Harnyuttanakorn, Surasak Chunsrivirot, Sittiporn Pattaradilokrat
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Plasmodium falciparum Malaria Vaccine Transmission-blocking Diversity Haplotype Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/9c262f8a73b44829941f35807dcd318d
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spelling	oai:doaj.org-article:9c262f8a73b44829941f35807dcd318d2021-11-14T12:25:22ZGlobal diversity of the gene encoding the Pfs25 protein—a Plasmodium falciparum transmission-blocking vaccine candidate10.1186/s13071-021-05078-61756-3305https://doaj.org/article/9c262f8a73b44829941f35807dcd318d2021-11-01T00:00:00Zhttps://doi.org/10.1186/s13071-021-05078-6https://doaj.org/toc/1756-3305Abstract Background 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. Methods 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. Results 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. Conclusions 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. Graphical AbstractPornpawee SookpongthaiKorawich UtayopasThassanai SitthiyothaTheerakamol PengsakulMorakot KaewthamasornKittikhun WangkanontPongchai HarnyuttanakornSurasak ChunsrivirotSittiporn PattaradilokratBMCarticlePlasmodium falciparumMalariaVaccineTransmission-blockingDiversityHaplotypeInfectious and parasitic diseasesRC109-216ENParasites & Vectors, Vol 14, Iss 1, Pp 1-19 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Plasmodium falciparum Malaria Vaccine Transmission-blocking Diversity Haplotype Infectious and parasitic diseases RC109-216
spellingShingle	Plasmodium falciparum Malaria Vaccine Transmission-blocking Diversity Haplotype Infectious and parasitic diseases RC109-216 Pornpawee Sookpongthai Korawich Utayopas Thassanai Sitthiyotha Theerakamol Pengsakul Morakot Kaewthamasorn Kittikhun Wangkanont Pongchai Harnyuttanakorn Surasak Chunsrivirot Sittiporn Pattaradilokrat Global diversity of the gene encoding the Pfs25 protein—a Plasmodium falciparum transmission-blocking vaccine candidate
description	Abstract Background 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. Methods 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. Results 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. Conclusions 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. Graphical Abstract
format	article
author	Pornpawee Sookpongthai Korawich Utayopas Thassanai Sitthiyotha Theerakamol Pengsakul Morakot Kaewthamasorn Kittikhun Wangkanont Pongchai Harnyuttanakorn Surasak Chunsrivirot Sittiporn Pattaradilokrat
author_facet	Pornpawee Sookpongthai Korawich Utayopas Thassanai Sitthiyotha Theerakamol Pengsakul Morakot Kaewthamasorn Kittikhun Wangkanont Pongchai Harnyuttanakorn Surasak Chunsrivirot Sittiporn Pattaradilokrat
author_sort	Pornpawee Sookpongthai
title	Global diversity of the gene encoding the Pfs25 protein—a Plasmodium falciparum transmission-blocking vaccine candidate
title_short	Global diversity of the gene encoding the Pfs25 protein—a Plasmodium falciparum transmission-blocking vaccine candidate
title_full	Global diversity of the gene encoding the Pfs25 protein—a Plasmodium falciparum transmission-blocking vaccine candidate
title_fullStr	Global diversity of the gene encoding the Pfs25 protein—a Plasmodium falciparum transmission-blocking vaccine candidate
title_full_unstemmed	Global diversity of the gene encoding the Pfs25 protein—a Plasmodium falciparum transmission-blocking vaccine candidate
title_sort	global diversity of the gene encoding the pfs25 protein—a plasmodium falciparum transmission-blocking vaccine candidate
publisher	BMC
publishDate	2021
url	https://doaj.org/article/9c262f8a73b44829941f35807dcd318d
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Global diversity of the gene encoding the Pfs25 protein—a Plasmodium falciparum transmission-blocking vaccine candidate

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