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

Amed Ouattara, Tuan  Tran, Safiatou Doumbo, Adams Matthew, Sonia Agrawal, Amadou Niangaly, Sara Nelson-Owens, Didier Doumtabé, Youssouf Tolo, Aissata Ongoiba, Shannon Takala-Harrison, Boubacar Traoré, Joana C. Silva, Peter D. Crompton, Ogobara K. Doumbo, Christopher V. Plowe

Research output: Contribution to journalArticle

Abstract

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 ofRH5in 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 (p = 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.

Original languageEnglish (US)
Pages (from-to)43-50
Number of pages8
JournalAmerican Journal of Tropical Medicine and Hygiene
Volume99
Issue number1
DOIs
StatePublished - Jan 1 2018

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Mali
Malaria Vaccines
Reticulocytes
Plasmodium falciparum
Haplotypes
Malaria
Vaccines
B-Lymphocyte Epitopes
Merozoites
Amino Acids
T-Lymphocyte Epitopes
Virulence
Plasmodium falciparum RH5 protein
Parasites
Cohort Studies
Fever
Nucleotides
Erythrocytes
Prospective Studies
Ligands

ASJC Scopus subject areas

  • Parasitology
  • Infectious Diseases
  • Virology

Cite this

Extent and Dynamics of Polymorphism in the Malaria Vaccine Candidate Plasmodium falciparum Reticulocyte-Binding Protein Homologue-5 in Kalifabougou, Mali. / Ouattara, Amed; Tran, Tuan ; Doumbo, Safiatou; Matthew, Adams; 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.

In: American Journal of Tropical Medicine and Hygiene, Vol. 99, No. 1, 01.01.2018, p. 43-50.

Research output: Contribution to journalArticle

Ouattara, A, Tran, T, Doumbo, S, Matthew, A, Agrawal, S, Niangaly, A, Nelson-Owens, S, Doumtabé, D, Tolo, Y, Ongoiba, A, Takala-Harrison, S, Traoré, B, Silva, JC, Crompton, PD, Doumbo, OK & Plowe, CV 2018, 'Extent and Dynamics of Polymorphism in the Malaria Vaccine Candidate Plasmodium falciparum Reticulocyte-Binding Protein Homologue-5 in Kalifabougou, Mali', American Journal of Tropical Medicine and Hygiene, vol. 99, no. 1, pp. 43-50. https://doi.org/10.4269/ajtmh.17-0737
Ouattara, Amed ; Tran, Tuan  ; Doumbo, Safiatou ; Matthew, Adams ; 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. In: American Journal of Tropical Medicine and Hygiene. 2018 ; Vol. 99, No. 1. pp. 43-50.
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AU - Doumbo, Safiatou

AU - Matthew, Adams

AU - Agrawal, Sonia

AU - Niangaly, Amadou

AU - Nelson-Owens, Sara

AU - Doumtabé, Didier

AU - Tolo, Youssouf

AU - Ongoiba, Aissata

AU - Takala-Harrison, Shannon

AU - Traoré, Boubacar

AU - Silva, Joana C.

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AU - Plowe, Christopher V.

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