Genetic polymorphisms in malaria vaccine candidate Plasmodium falciparum reticulocyte-binding protein homologue-5 among populations in Lagos, Nigeria

Olusola Ajibaye, Akinniyi Osuntoki, Emmanuel Balogun, Yetunde Olukosi, Bamidele Iwalokun, Kolapo Oyebola, Kenji Hikosaka, Yoh-ichi Watanabe, Godwin Ebiloma, Kiyoshi Kita, Alfred Amambua-ngwa

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Abstract

Background
Vaccines 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.
Methods
One 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.
Results
Sequence 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.
Conclusions
This 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.
Original languageEnglish
Number of pages12
JournalMalaria Journal
Volume19
Issue number6
DOIs
Publication statusPublished - 6 Jan 2020

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Malaria Vaccines
Genetic Polymorphisms
Nigeria
T-Lymphocyte Epitopes
Population
B-Lymphocyte Epitopes
Plasmodium falciparum
Vaccines
Haplotypes
Major Histocompatibility Complex
Peptides
Single Nucleotide Polymorphism
Genes
Merozoites
Plasmodium falciparum RH5 protein
Antigens
Population Genetics
Malaria
Cysteine
Sequence Analysis

Cite this

Ajibaye, Olusola ; Osuntoki, Akinniyi ; Balogun, Emmanuel ; Olukosi, Yetunde ; Iwalokun, Bamidele ; Oyebola, Kolapo ; Hikosaka, Kenji ; Watanabe, Yoh-ichi ; Ebiloma, Godwin ; Kita, Kiyoshi ; Amambua-ngwa, Alfred. / Genetic polymorphisms in malaria vaccine candidate Plasmodium falciparum reticulocyte-binding protein homologue-5 among populations in Lagos, Nigeria. In: Malaria Journal. 2020 ; Vol. 19, No. 6.
@article{1980458af3f74457a826dbe15b9c10dd,
title = "Genetic polymorphisms in malaria vaccine candidate Plasmodium falciparum reticulocyte-binding protein homologue-5 among populations in Lagos, Nigeria",
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.",
author = "Olusola Ajibaye and Akinniyi Osuntoki and Emmanuel Balogun and Yetunde Olukosi and Bamidele Iwalokun and Kolapo Oyebola and Kenji Hikosaka and Yoh-ichi Watanabe and Godwin Ebiloma and Kiyoshi Kita and Alfred Amambua-ngwa",
year = "2020",
month = "1",
day = "6",
doi = "10.1186/s12936-019-3096-0",
language = "English",
volume = "19",
journal = "Malaria Journal",
issn = "1475-2875",
publisher = "BioMed Central Ltd.",
number = "6",

}

Ajibaye, O, Osuntoki, A, Balogun, E, Olukosi, Y, Iwalokun, B, Oyebola, K, Hikosaka, K, Watanabe, Y, Ebiloma, G, Kita, K & Amambua-ngwa, A 2020, 'Genetic polymorphisms in malaria vaccine candidate Plasmodium falciparum reticulocyte-binding protein homologue-5 among populations in Lagos, Nigeria', Malaria Journal, vol. 19, no. 6. https://doi.org/10.1186/s12936-019-3096-0

Genetic polymorphisms in malaria vaccine candidate Plasmodium falciparum reticulocyte-binding protein homologue-5 among populations in Lagos, Nigeria. / Ajibaye, Olusola; Osuntoki, Akinniyi ; Balogun, Emmanuel ; Olukosi, Yetunde ; Iwalokun, Bamidele ; Oyebola, Kolapo ; Hikosaka, Kenji; Watanabe, Yoh-ichi; Ebiloma, Godwin ; Kita, Kiyoshi; Amambua-ngwa, Alfred.

In: Malaria Journal, Vol. 19, No. 6, 06.01.2020.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genetic polymorphisms in malaria vaccine candidate Plasmodium falciparum reticulocyte-binding protein homologue-5 among populations in Lagos, Nigeria

AU - Ajibaye, Olusola

AU - Osuntoki, Akinniyi

AU - Balogun, Emmanuel

AU - Olukosi, Yetunde

AU - Iwalokun, Bamidele

AU - Oyebola, Kolapo

AU - Hikosaka, Kenji

AU - Watanabe, Yoh-ichi

AU - Ebiloma, Godwin

AU - Kita, Kiyoshi

AU - Amambua-ngwa, Alfred

PY - 2020/1/6

Y1 - 2020/1/6

N2 - 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.

AB - 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.

U2 - 10.1186/s12936-019-3096-0

DO - 10.1186/s12936-019-3096-0

M3 - Article

VL - 19

JO - Malaria Journal

JF - Malaria Journal

SN - 1475-2875

IS - 6

ER -