ArticleMalaria journal2020
Genetic polymorphisms in malaria vaccine candidate Plasmodium falciparum reticulocyte-binding protein homologue-5 among populations in Lagos, Nigeria.
Article in Malaria journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20 citing papers in PubMed, 31 citations in OpenAlex.
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- The N-terminal region of malaria vaccine candidate asparagine-rich merozoite antigen is immunodominant and targeted by polyreactive antibodies.Disease models & mechanisms · 2026Article
- The N-terminal region of malaria vaccine candidatebioRxiv : the preprint server for biology · 2025Article
- Malaria vaccines: Current developments and immunological insights.New microbes and new infections · 2025Article
- Immunoinformatics-Based Multi-Epitope Vaccine Design AgainstHealth science reports · 2025Article
- Genetic diversity and natural selection of Plasmodium falciparum Pf41 vaccine candidate in clinical isolates from Senegal.Scientific reports · 2025Article
- Article
- Vaccine-induced human monoclonal antibodies to PfRH5 show broadly neutralizing activity against P. falciparum clinical isolates.NPJ vaccines · 2024Article
- Detection of novelFrontiers in cellular and infection microbiology · 2024Article
- Immunization with PfGBP130 generates antibodies that inhibit RBC invasion byFrontiers in immunology · 2024Article
- Estimation of PfRh5-based vaccine efficacy in asymptomaticFrontiers in immunology · 2024Article
- Malaria Genomics, Vaccine Development, and Microbiome.Pathogens (Basel, Switzerland) · 2023Review
- Limited genetic variations of the Rh5-CyRPA-Ripr invasion complex inFrontiers in tropical diseases · 2023Article
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- Structure-guided insights into potential function of novel genetic variants in the malaria vaccine candidate PfRh5.Scientific reports · 2022Article
- Geographical distribution and genetic diversity of Plasmodium vivax reticulocyte binding protein 1a correlates with patient antigenicity.PLoS neglected tropical diseases · 2022Article
- Stereo electronic principles for selecting fully-protective, chemically-synthesised malaria vaccines.Frontiers in immunology · 2022Review
- The Plasmodium falciparum Rh5 invasion protein complex reveals an excess of rare variant mutations.Malaria journal · 2021Article
- Assessing the functional impact of PfRh5 genetic diversity on ex vivo erythrocyte invasion inhibition.Scientific reports · 2021Article
- Hotspots inInternational journal of molecular sciences · 2020Review
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11 authors at 7 institutions in 4 countries.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundVaccines are the most reliable alternative to elicit sterile immunity against malaria but their development has been hindered by polymorphisms and strain-specificity in previously studied antigens. New vaccine candidates are therefore urgently needed. Highly conserved Plasmodium falciparum reticulocyte-binding protein homologue-5 (PfRH5) has been identified as a potential candidate for anti-disease vaccine development. PfRH5 is essential for erythrocyte invasion by merozoites and crucial for parasite survival. However, there is paucity of data on the extent of genetic variations on PfRH5 in field isolates of Plasmodium falciparum. This study described genetic polymorphisms at the high affinity binding polypeptides (HABPs) 36718, 36727, 36728 of PfRH5 in Nigerian isolates of P. falciparum. This study tested the hypothesis that only specific conserved B and T cell epitopes on PfRH5 HABPs are crucial for vaccine development.
methodsOne hundred and ninety-five microscopically confirmed P. falciparum samples collected in a prospective cross-sectional study of three different populations in Lagos, Nigeria. Genetic diversity and haplotype construct of Pfrh5 gene were determined using bi-directional sequencing approach. Tajima's D and the ratio of nonsynonymous vs synonymous mutations were utilized to estimate the extent of balancing and directional selection in the pfrh5 gene.
resultsSequence analysis revealed three haplotypes of PfRH5 with negative Tajima's D and dN/dS value of - 1.717 and 0.011 ± 0.020, respectively. A single nucleotide polymorphism, SNP (G → A) at position 608 was observed, which resulted in a change of the amino acid cysteine at position 203 to tyrosine. Haplotype and nucleotide diversities were 0.318 ± 0.016 and 0.0046 ± 0.0001 while inter-population genetic differentiation ranged from 0.007 to 0.037. Five polypeptide variants were identified, the most frequent being KTKYH with a frequency of 51.3%. One B-cell epitope, 151 major histocompatibility complex (MHC) class II T-cell epitopes, four intrinsically unstructured regions (IURs) and six MHC class I T-cell epitopes were observed in the study. Phylogenetic analysis of the sequences showed clustering and evidence of evolutionary relationship with 3D7, PAS-2 and FCB-2 RH5 sequences.
conclusionsThis study has revealed low level of genetic polymorphisms in PfRH5 antigen with B- and T-cell epitopes in intrinsically unstructured regions along the PfRH5 gene in Lagos, Nigeria. A broader investigation is however required in other parts of the country to support the possible inclusion of PfRH5 in a cross-protective multi-component vaccine.
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