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....
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-11-01
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| Series: | Malaria Journal |
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| Online Access: | https://doi.org/10.1186/s12936-021-03971-0 |
| _version_ | 1818838365757243392 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T03:37:15Z |
| format | Article |
| id | doaj.art-c38b2d8c550f4b60b6ee2714a1922d8a |
| institution | Directory Open Access Journal |
| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-12-19T03:37:15Z |
| publishDate | 2021-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Malaria Journal |
| spelling | doaj.art-c38b2d8c550f4b60b6ee2714a1922d8a2022-12-21T20:37:20ZengBMCMalaria Journal1475-28752021-11-0120111210.1186/s12936-021-03971-0Assessment of genetic diversity of Plasmodium falciparum circumsporozoite protein in Sudan: the RTS,S leading malaria vaccine candidateNouh Saad Mohamed0Hanadi AbdElbagi1Ahad R. Elsadig2Abdalla Elssir Ahmed3Yassir Osman Mohammed4Lubna Taj Elssir5Mohammed-Ahmed B. Elnour6Yousif Ali7Mohamed S. Ali8Omnia Altahir9Mustafa Abubakr10Emmanuel Edwar Siddig11Ayman Ahmed12Rihab Ali Omer13Department of Parasitology and Medical Entomology, Tropical Medicine Research Institute, National Centre for ResearchMolecular Biology Unit, Sirius Training and Research CentreEl-Raqi Hospital, National UniversityMolecular Biology Unit, Sirius Training and Research CentreDepartment of Parasitology and Medical Entomology, Tropical Medicine Research Institute, National Centre for ResearchDepartment of Parasitology and Medical Entomology, Tropical Medicine Research Institute, National Centre for ResearchDepartment of Parasitology and Medical Entomology, Tropical Medicine Research Institute, National Centre for ResearchHealth Emergencies and Epidemics Control General Directorate, Sudan Federal Ministry of HealthFaculty of Medicine, EL-Neelain UniversityDepartment of Parasitology and Medical Entomology, Tropical Medicine Research Institute, National Centre for ResearchDepartment of the Integrated Vector Management (IVM), Federal Ministry of HealthMycetoma Research Center, University of KhartoumMolecular Biology Unit, Sirius Training and Research CentrePediatric Epidemiology, Clinic and Polyclinic for Child and Adolescent Medicine, Medical Faculty, University of LeipzigAbstract 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.https://doi.org/10.1186/s12936-021-03971-0MalariaPlasmodium falciparum circumsporozoite protein (PfCSP)VaccineRTS,SHapdN-terminal, central repeats, and C-terminal regions |
| spellingShingle | 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 Malaria Journal Malaria Plasmodium falciparum circumsporozoite protein (PfCSP) Vaccine RTS,S Hapd N-terminal, central repeats, and C-terminal regions |
| title | 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_short | 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 |
| topic | Malaria Plasmodium falciparum circumsporozoite protein (PfCSP) Vaccine RTS,S Hapd N-terminal, central repeats, and C-terminal regions |
| url | https://doi.org/10.1186/s12936-021-03971-0 |
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