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Extent and Dynamics of Polymorphism in the Malaria Vaccine Candidate Plasmodium falciparum Reticulocyte–Binding Protein Homologue-5 in Kalifabougou, Mali

Reticulocyte-binding homologues (RH) are a ligand family that mediates merozoite invasion of erythrocytes in Plasmodium falciparum. Among the five members of this family identified so far, only P. falciparum reticulocyte–binding homologue-5 (PfRH5) has been found to be essential for parasite surviva...

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Autores principales: Ouattara, Amed, Tran, Tuan M., Doumbo, Safiatou, Adams, Matthew, Agrawal, Sonia, Niangaly, Amadou, Nelson-Owens, Sara, Doumtabé, Didier, Tolo, Youssouf, Ongoiba, Aissata, Takala-Harrison, Shannon, Traoré, Boubacar, Silva, Joana C., Crompton, Peter D., Doumbo, Ogobara K., Plowe, Christopher V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society of Tropical Medicine and Hygiene 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6085788/
https://www.ncbi.nlm.nih.gov/pubmed/29848401
http://dx.doi.org/10.4269/ajtmh.17-0737
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author Ouattara, Amed
Tran, Tuan M.
Doumbo, Safiatou
Adams, Matthew
Agrawal, Sonia
Niangaly, Amadou
Nelson-Owens, Sara
Doumtabé, Didier
Tolo, Youssouf
Ongoiba, Aissata
Takala-Harrison, Shannon
Traoré, Boubacar
Silva, Joana C.
Crompton, Peter D.
Doumbo, Ogobara K.
Plowe, Christopher V.
author_facet Ouattara, Amed
Tran, Tuan M.
Doumbo, Safiatou
Adams, Matthew
Agrawal, Sonia
Niangaly, Amadou
Nelson-Owens, Sara
Doumtabé, Didier
Tolo, Youssouf
Ongoiba, Aissata
Takala-Harrison, Shannon
Traoré, Boubacar
Silva, Joana C.
Crompton, Peter D.
Doumbo, Ogobara K.
Plowe, Christopher V.
author_sort Ouattara, Amed
collection PubMed
description Reticulocyte-binding homologues (RH) are a ligand family that mediates merozoite invasion of erythrocytes in Plasmodium falciparum. Among the five members of this family identified so far, only P. falciparum reticulocyte–binding homologue-5 (PfRH5) has been found to be essential for parasite survival across strains that differ in virulence and route of host-cell invasion. Based on its essential role in invasion and early evidence of sequence conservation, PfRH5 has been prioritized for development as a vaccine candidate. However, little is known about the extent of genetic variability of RH5 in the field and the potential impact of such diversity on clinical outcomes or on vaccine evasion. Samples collected during a prospective cohort study of malaria incidence conducted in Kalifabougou, in southwestern Mali, were used to estimate genetic diversity, measure haplotype prevalence, and assess the within-host dynamics of PfRH5 variants over time and in relation to clinical malaria. A total of 10 nonsynonymous polymorphic sites were identified in the Pfrh5 gene, resulting in 13 haplotypes encoding unique protein variants. Four of these variants have not been previously observed. Plasmodium falciparum reticulocyte–binding homologue-5 had low amino acid haplotype (h = 0.58) and nucleotide (π = 0.00061) diversity. By contrast to other leading blood-stage malaria vaccine candidate antigens, amino acid differences were not associated with changes in the risk of febrile malaria in consecutive infections. Conserved B- and T-cell epitopes were identified. These results support the prioritization of PfRH5 for possible inclusion in a broadly cross-protective vaccine.
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spelling pubmed-60857882018-08-13 Extent and Dynamics of Polymorphism in the Malaria Vaccine Candidate Plasmodium falciparum Reticulocyte–Binding Protein Homologue-5 in Kalifabougou, Mali Ouattara, Amed Tran, Tuan M. Doumbo, Safiatou Adams, Matthew Agrawal, Sonia Niangaly, Amadou Nelson-Owens, Sara Doumtabé, Didier Tolo, Youssouf Ongoiba, Aissata Takala-Harrison, Shannon Traoré, Boubacar Silva, Joana C. Crompton, Peter D. Doumbo, Ogobara K. Plowe, Christopher V. Am J Trop Med Hyg Articles Reticulocyte-binding homologues (RH) are a ligand family that mediates merozoite invasion of erythrocytes in Plasmodium falciparum. Among the five members of this family identified so far, only P. falciparum reticulocyte–binding homologue-5 (PfRH5) has been found to be essential for parasite survival across strains that differ in virulence and route of host-cell invasion. Based on its essential role in invasion and early evidence of sequence conservation, PfRH5 has been prioritized for development as a vaccine candidate. However, little is known about the extent of genetic variability of RH5 in the field and the potential impact of such diversity on clinical outcomes or on vaccine evasion. Samples collected during a prospective cohort study of malaria incidence conducted in Kalifabougou, in southwestern Mali, were used to estimate genetic diversity, measure haplotype prevalence, and assess the within-host dynamics of PfRH5 variants over time and in relation to clinical malaria. A total of 10 nonsynonymous polymorphic sites were identified in the Pfrh5 gene, resulting in 13 haplotypes encoding unique protein variants. Four of these variants have not been previously observed. Plasmodium falciparum reticulocyte–binding homologue-5 had low amino acid haplotype (h = 0.58) and nucleotide (π = 0.00061) diversity. By contrast to other leading blood-stage malaria vaccine candidate antigens, amino acid differences were not associated with changes in the risk of febrile malaria in consecutive infections. Conserved B- and T-cell epitopes were identified. These results support the prioritization of PfRH5 for possible inclusion in a broadly cross-protective vaccine. The American Society of Tropical Medicine and Hygiene 2018-07 2018-05-29 /pmc/articles/PMC6085788/ /pubmed/29848401 http://dx.doi.org/10.4269/ajtmh.17-0737 Text en © The American Society of Tropical Medicine and Hygiene This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Articles
Ouattara, Amed
Tran, Tuan M.
Doumbo, Safiatou
Adams, Matthew
Agrawal, Sonia
Niangaly, Amadou
Nelson-Owens, Sara
Doumtabé, Didier
Tolo, Youssouf
Ongoiba, Aissata
Takala-Harrison, Shannon
Traoré, Boubacar
Silva, Joana C.
Crompton, Peter D.
Doumbo, Ogobara K.
Plowe, Christopher V.
Extent and Dynamics of Polymorphism in the Malaria Vaccine Candidate Plasmodium falciparum Reticulocyte–Binding Protein Homologue-5 in Kalifabougou, Mali
title Extent and Dynamics of Polymorphism in the Malaria Vaccine Candidate Plasmodium falciparum Reticulocyte–Binding Protein Homologue-5 in Kalifabougou, Mali
title_full Extent and Dynamics of Polymorphism in the Malaria Vaccine Candidate Plasmodium falciparum Reticulocyte–Binding Protein Homologue-5 in Kalifabougou, Mali
title_fullStr Extent and Dynamics of Polymorphism in the Malaria Vaccine Candidate Plasmodium falciparum Reticulocyte–Binding Protein Homologue-5 in Kalifabougou, Mali
title_full_unstemmed Extent and Dynamics of Polymorphism in the Malaria Vaccine Candidate Plasmodium falciparum Reticulocyte–Binding Protein Homologue-5 in Kalifabougou, Mali
title_short Extent and Dynamics of Polymorphism in the Malaria Vaccine Candidate Plasmodium falciparum Reticulocyte–Binding Protein Homologue-5 in Kalifabougou, Mali
title_sort extent and dynamics of polymorphism in the malaria vaccine candidate plasmodium falciparum reticulocyte–binding protein homologue-5 in kalifabougou, mali
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6085788/
https://www.ncbi.nlm.nih.gov/pubmed/29848401
http://dx.doi.org/10.4269/ajtmh.17-0737
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