Assessment of genetic diversity of Plasmodium falciparum circumsporozoite protein in Sudan: the RTS,S leading malaria vaccine candidate

Abstract Background The currently used malaria vaccine, RTS,S, is designed based on the Plasmodium falciparum circumsporozoite protein (PfCSP). The pfcsp gene, besides having different polymorphic patterns, can vary between P. falciparum isolates due to geographical origin and host immune response....

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Autores principales:	Nouh Saad Mohamed, Hanadi AbdElbagi, Ahad R. Elsadig, Abdalla Elssir Ahmed, Yassir Osman Mohammed, Lubna Taj Elssir, Mohammed-Ahmed B. Elnour, Yousif Ali, Mohamed S. Ali, Omnia Altahir, Mustafa Abubakr, Emmanuel Edwar Siddig, Ayman Ahmed, Rihab Ali Omer
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Malaria Plasmodium falciparum circumsporozoite protein (PfCSP) Vaccine RTS,S Hapd N-terminal, central repeats, and C-terminal regions Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/c38b2d8c550f4b60b6ee2714a1922d8a
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spelling	oai:doaj.org-article:c38b2d8c550f4b60b6ee2714a1922d8a2021-11-14T12:33:46ZAssessment of genetic diversity of Plasmodium falciparum circumsporozoite protein in Sudan: the RTS,S leading malaria vaccine candidate10.1186/s12936-021-03971-01475-2875https://doaj.org/article/c38b2d8c550f4b60b6ee2714a1922d8a2021-11-01T00:00:00Zhttps://doi.org/10.1186/s12936-021-03971-0https://doaj.org/toc/1475-2875Abstract Background The currently used malaria vaccine, RTS,S, is designed based on the Plasmodium falciparum circumsporozoite protein (PfCSP). The pfcsp gene, besides having different polymorphic patterns, can vary between P. falciparum isolates due to geographical origin and host immune response. Such aspects are essential when considering the deployment of the RTS,S vaccine in a certain region. Therefore, this study assessed the genetic diversity of P. falciparum in Sudan based on the pfcsp gene by investigating the diversity at the N-terminal, central repeat, and the C-terminal regions. Methods A cross-sectional molecular study was conducted; P. falciparum isolates were collected from different health centres in Khartoum State between January and December 2019. During the study period, a total of 261 febrile patients were recruited. Malaria diagnosis was made by expert microscopists using Giemsa-stained thick and thin blood films. DNA samples were examined by the semi-nested polymerase chain reaction (PCR). Single clonal infection of the confirmed P. falciparum cases, were used to amplify the pfcsp gene. The amplified amplicons of pfcsp have been sequenced using the Sanger dideoxy method. The obtained sequences of pfcsp nucleotide diversity parameters including the numbers of haplotypes (Hap), haplotypes diversity (Hapd), the average number of nucleotide differences between two sequences (p), and the numbers of segregating sites (S) were obtained. The haplotype networks were constructed using the online tcsBU software. Natural selection theory was also tested on pfcsp using Fuand Li’s D, Fuand Li’s F statistics, and Tajima’s D test using DnaSP. Results In comparison with the different pfcsp reference strains, the Sudanese isolates showed high similarity with other African isolates. The results of the N-terminal region showed the presence of 2 different haplotypes with a Hapd of 0.425 ± 0.00727. The presence of the unique insertion of NNNGDNGREGKDEDKRDGNN was reported. The KLKQP motif was conserved in all the studied isolates. At the central repeat region, 11 haplotypes were seen with a Hapd of 0.779 ± 0.00097. The analysis of the genetic diversity in the C-terminal region showed the presence of 10 haplotypes with a Hapd of 0.457 ± 0.073. Several non-synonymous amino acids changes were also seen at the Th2R and the Th3R T-cell epitope regions including T317K, E317K, Q318E, K321N, I322K, T322K, R322K, K324Q, I327L, G352N, S354P, R355K, N356D, Q357E, and E361A. Conclusions In this study, the results indicated a high conservation at the pfcsp gene. This may further contribute in understanding the genetic polymorphisms of P. falciparum prior to the deployment of the RTS,S vaccine in Sudan.Nouh Saad MohamedHanadi AbdElbagiAhad R. ElsadigAbdalla Elssir AhmedYassir Osman MohammedLubna Taj ElssirMohammed-Ahmed B. ElnourYousif AliMohamed S. AliOmnia AltahirMustafa AbubakrEmmanuel Edwar SiddigAyman AhmedRihab Ali OmerBMCarticleMalariaPlasmodium falciparum circumsporozoite protein (PfCSP)VaccineRTS,SHapdN-terminal, central repeats, and C-terminal regionsArctic medicine. Tropical medicineRC955-962Infectious and parasitic diseasesRC109-216ENMalaria Journal, Vol 20, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Malaria Plasmodium falciparum circumsporozoite protein (PfCSP) Vaccine RTS,S Hapd N-terminal, central repeats, and C-terminal regions Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216
spellingShingle	Malaria Plasmodium falciparum circumsporozoite protein (PfCSP) Vaccine RTS,S Hapd N-terminal, central repeats, and C-terminal regions Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Nouh Saad Mohamed Hanadi AbdElbagi Ahad R. Elsadig Abdalla Elssir Ahmed Yassir Osman Mohammed Lubna Taj Elssir Mohammed-Ahmed B. Elnour Yousif Ali Mohamed S. Ali Omnia Altahir Mustafa Abubakr Emmanuel Edwar Siddig Ayman Ahmed Rihab Ali Omer Assessment of genetic diversity of Plasmodium falciparum circumsporozoite protein in Sudan: the RTS,S leading malaria vaccine candidate
description	Abstract Background The currently used malaria vaccine, RTS,S, is designed based on the Plasmodium falciparum circumsporozoite protein (PfCSP). The pfcsp gene, besides having different polymorphic patterns, can vary between P. falciparum isolates due to geographical origin and host immune response. Such aspects are essential when considering the deployment of the RTS,S vaccine in a certain region. Therefore, this study assessed the genetic diversity of P. falciparum in Sudan based on the pfcsp gene by investigating the diversity at the N-terminal, central repeat, and the C-terminal regions. Methods A cross-sectional molecular study was conducted; P. falciparum isolates were collected from different health centres in Khartoum State between January and December 2019. During the study period, a total of 261 febrile patients were recruited. Malaria diagnosis was made by expert microscopists using Giemsa-stained thick and thin blood films. DNA samples were examined by the semi-nested polymerase chain reaction (PCR). Single clonal infection of the confirmed P. falciparum cases, were used to amplify the pfcsp gene. The amplified amplicons of pfcsp have been sequenced using the Sanger dideoxy method. The obtained sequences of pfcsp nucleotide diversity parameters including the numbers of haplotypes (Hap), haplotypes diversity (Hapd), the average number of nucleotide differences between two sequences (p), and the numbers of segregating sites (S) were obtained. The haplotype networks were constructed using the online tcsBU software. Natural selection theory was also tested on pfcsp using Fuand Li’s D, Fuand Li’s F statistics, and Tajima’s D test using DnaSP. Results In comparison with the different pfcsp reference strains, the Sudanese isolates showed high similarity with other African isolates. The results of the N-terminal region showed the presence of 2 different haplotypes with a Hapd of 0.425 ± 0.00727. The presence of the unique insertion of NNNGDNGREGKDEDKRDGNN was reported. The KLKQP motif was conserved in all the studied isolates. At the central repeat region, 11 haplotypes were seen with a Hapd of 0.779 ± 0.00097. The analysis of the genetic diversity in the C-terminal region showed the presence of 10 haplotypes with a Hapd of 0.457 ± 0.073. Several non-synonymous amino acids changes were also seen at the Th2R and the Th3R T-cell epitope regions including T317K, E317K, Q318E, K321N, I322K, T322K, R322K, K324Q, I327L, G352N, S354P, R355K, N356D, Q357E, and E361A. Conclusions In this study, the results indicated a high conservation at the pfcsp gene. This may further contribute in understanding the genetic polymorphisms of P. falciparum prior to the deployment of the RTS,S vaccine in Sudan.
format	article
author	Nouh Saad Mohamed Hanadi AbdElbagi Ahad R. Elsadig Abdalla Elssir Ahmed Yassir Osman Mohammed Lubna Taj Elssir Mohammed-Ahmed B. Elnour Yousif Ali Mohamed S. Ali Omnia Altahir Mustafa Abubakr Emmanuel Edwar Siddig Ayman Ahmed Rihab Ali Omer
author_facet	Nouh Saad Mohamed Hanadi AbdElbagi Ahad R. Elsadig Abdalla Elssir Ahmed Yassir Osman Mohammed Lubna Taj Elssir Mohammed-Ahmed B. Elnour Yousif Ali Mohamed S. Ali Omnia Altahir Mustafa Abubakr Emmanuel Edwar Siddig Ayman Ahmed Rihab Ali Omer
author_sort	Nouh Saad Mohamed
title	Assessment of genetic diversity of Plasmodium falciparum circumsporozoite protein in Sudan: the RTS,S leading malaria vaccine candidate
title_short	Assessment of genetic diversity of Plasmodium falciparum circumsporozoite protein in Sudan: the RTS,S leading malaria vaccine candidate
title_full	Assessment of genetic diversity of Plasmodium falciparum circumsporozoite protein in Sudan: the RTS,S leading malaria vaccine candidate
title_fullStr	Assessment of genetic diversity of Plasmodium falciparum circumsporozoite protein in Sudan: the RTS,S leading malaria vaccine candidate
title_full_unstemmed	Assessment of genetic diversity of Plasmodium falciparum circumsporozoite protein in Sudan: the RTS,S leading malaria vaccine candidate
title_sort	assessment of genetic diversity of plasmodium falciparum circumsporozoite protein in sudan: the rts,s leading malaria vaccine candidate
publisher	BMC
publishDate	2021
url	https://doaj.org/article/c38b2d8c550f4b60b6ee2714a1922d8a
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Assessment of genetic diversity of Plasmodium falciparum circumsporozoite protein in Sudan: the RTS,S leading malaria vaccine candidate

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