Genetic variation of the Plasmodium falciparum circumsporozoite protein in parasite isolates from Homabay County in Kenya
The Plasmodium falciparum Circumsporozoite Protein (PfCSP) has been used in developing the RTS,S, and R21 malaria vaccines. However, genetic polymorphisms within Pfcsp compromise the effectiveness of the vaccine. Thus, it is essential to continuously assess the genetic diversity of Pfcsp, especially...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-04-01
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| Series: | Frontiers in Parasitology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fpara.2024.1346017/full |
| _version_ | 1827157594932772864 |
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| author | Michael Maina Michael Maina Sebastian Musundi Josiah Kuja Harrison Waweru Harrison Waweru Daniel Kiboi Bernard N. Kanoi Jesse Gitaka |
| author_facet | Michael Maina Michael Maina Sebastian Musundi Josiah Kuja Harrison Waweru Harrison Waweru Daniel Kiboi Bernard N. Kanoi Jesse Gitaka |
| author_sort | Michael Maina |
| collection | DOAJ |
| description | The Plasmodium falciparum Circumsporozoite Protein (PfCSP) has been used in developing the RTS,S, and R21 malaria vaccines. However, genetic polymorphisms within Pfcsp compromise the effectiveness of the vaccine. Thus, it is essential to continuously assess the genetic diversity of Pfcsp, especially when deploying it across different geographical regions. In this study, we assessed the genetic diversity of the Pfcsp on isolates from Homabay County, a malaria-endemic region in western Kenya, and compared it against other isolates from Kenya. We extracted DNA from 27 microscopically confirmed P. falciparum positive samples and conducted Illumina sequencing to generate paired-end short reads. The sequences were then mapped to the Pf3D7 reference genome, and genetic variation was analyzed using bcftools. Additionally, we retrieved isolates from two other malaria-endemic regions in Kenya, Kisumu (n=58) and Kilifi (n=596), from MalariaGEN version 7 and compared their genetic diversity and natural selection. We also evaluated the predicted binding affinities for HLA class I and II supertype alleles for the identified haplotypes using NetMHCpan and NetMHCIIpan. Our results show that the N-terminal of PfCSP was relatively conserved with a notable mutation at A98G across all isolates. The number of NANP repeats varied across the three Kenyan sites within the central repeat region. Furthermore, the C-terminal region showed polymorphism within the Th2R and Th3R regions. Haplotype network analysis of the Kenyan isolates revealed 69 haplotypes, with the 3D7 reference being found in the most prevalent haplotype. When assessing the predicted binding affinities between supertypes in HLA class I and II with the identified haplotypes, we observed stronger predicted binding affinities to multiple haplotypes except for those containing the 3D7 reference. The results suggest the need to take into account the existing changes occurring in Pfcsp while developing malaria vaccines. |
| first_indexed | 2024-04-24T12:03:14Z |
| format | Article |
| id | doaj.art-aa9fea7988954c46af79d139278ccbaa |
| institution | Directory Open Access Journal |
| issn | 2813-2424 |
| language | English |
| last_indexed | 2025-03-20T23:27:50Z |
| publishDate | 2024-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Parasitology |
| spelling | doaj.art-aa9fea7988954c46af79d139278ccbaa2024-08-03T14:43:51ZengFrontiers Media S.A.Frontiers in Parasitology2813-24242024-04-01310.3389/fpara.2024.13460171346017Genetic variation of the Plasmodium falciparum circumsporozoite protein in parasite isolates from Homabay County in KenyaMichael Maina0Michael Maina1Sebastian Musundi2Josiah Kuja3Harrison Waweru4Harrison Waweru5Daniel Kiboi6Bernard N. Kanoi7Jesse Gitaka8Centre for Malaria Elimination, Institute of Tropical Medicine, Mount Kenya University, Thika, KenyaDepartment of Biochemistry, Jomo Kenyatta University of Agriculture and Technology, Nairobi, KenyaCentre for Malaria Elimination, Institute of Tropical Medicine, Mount Kenya University, Thika, KenyaCentre for Malaria Elimination, Institute of Tropical Medicine, Mount Kenya University, Thika, KenyaCentre for Malaria Elimination, Institute of Tropical Medicine, Mount Kenya University, Thika, KenyaDepartment of Biochemistry, Jomo Kenyatta University of Agriculture and Technology, Nairobi, KenyaDepartment of Biochemistry, Jomo Kenyatta University of Agriculture and Technology, Nairobi, KenyaCentre for Malaria Elimination, Institute of Tropical Medicine, Mount Kenya University, Thika, KenyaCentre for Malaria Elimination, Institute of Tropical Medicine, Mount Kenya University, Thika, KenyaThe Plasmodium falciparum Circumsporozoite Protein (PfCSP) has been used in developing the RTS,S, and R21 malaria vaccines. However, genetic polymorphisms within Pfcsp compromise the effectiveness of the vaccine. Thus, it is essential to continuously assess the genetic diversity of Pfcsp, especially when deploying it across different geographical regions. In this study, we assessed the genetic diversity of the Pfcsp on isolates from Homabay County, a malaria-endemic region in western Kenya, and compared it against other isolates from Kenya. We extracted DNA from 27 microscopically confirmed P. falciparum positive samples and conducted Illumina sequencing to generate paired-end short reads. The sequences were then mapped to the Pf3D7 reference genome, and genetic variation was analyzed using bcftools. Additionally, we retrieved isolates from two other malaria-endemic regions in Kenya, Kisumu (n=58) and Kilifi (n=596), from MalariaGEN version 7 and compared their genetic diversity and natural selection. We also evaluated the predicted binding affinities for HLA class I and II supertype alleles for the identified haplotypes using NetMHCpan and NetMHCIIpan. Our results show that the N-terminal of PfCSP was relatively conserved with a notable mutation at A98G across all isolates. The number of NANP repeats varied across the three Kenyan sites within the central repeat region. Furthermore, the C-terminal region showed polymorphism within the Th2R and Th3R regions. Haplotype network analysis of the Kenyan isolates revealed 69 haplotypes, with the 3D7 reference being found in the most prevalent haplotype. When assessing the predicted binding affinities between supertypes in HLA class I and II with the identified haplotypes, we observed stronger predicted binding affinities to multiple haplotypes except for those containing the 3D7 reference. The results suggest the need to take into account the existing changes occurring in Pfcsp while developing malaria vaccines.https://www.frontiersin.org/articles/10.3389/fpara.2024.1346017/fullcircumsporozoite proteinvaccinesgenetic diversityPlasmodium falciparummalaria |
| spellingShingle | Michael Maina Michael Maina Sebastian Musundi Josiah Kuja Harrison Waweru Harrison Waweru Daniel Kiboi Bernard N. Kanoi Jesse Gitaka Genetic variation of the Plasmodium falciparum circumsporozoite protein in parasite isolates from Homabay County in Kenya Frontiers in Parasitology circumsporozoite protein vaccines genetic diversity Plasmodium falciparum malaria |
| title | Genetic variation of the Plasmodium falciparum circumsporozoite protein in parasite isolates from Homabay County in Kenya |
| title_full | Genetic variation of the Plasmodium falciparum circumsporozoite protein in parasite isolates from Homabay County in Kenya |
| title_fullStr | Genetic variation of the Plasmodium falciparum circumsporozoite protein in parasite isolates from Homabay County in Kenya |
| title_full_unstemmed | Genetic variation of the Plasmodium falciparum circumsporozoite protein in parasite isolates from Homabay County in Kenya |
| title_short | Genetic variation of the Plasmodium falciparum circumsporozoite protein in parasite isolates from Homabay County in Kenya |
| title_sort | genetic variation of the plasmodium falciparum circumsporozoite protein in parasite isolates from homabay county in kenya |
| topic | circumsporozoite protein vaccines genetic diversity Plasmodium falciparum malaria |
| url | https://www.frontiersin.org/articles/10.3389/fpara.2024.1346017/full |
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