scholarly journals Genetic diversity and neutral selection in Plasmodium vivax erythrocyte binding protein correlates with patient antigenicity

2020 ◽  
Vol 14 (7) ◽  
pp. e0008202 ◽  
Author(s):  
Jin-Hee Han ◽  
Jee-Sun Cho ◽  
Jessica J. Y. Ong ◽  
Ji-Hoon Park ◽  
Myat Htut Nyunt ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Vivax ◽  
Binding Protein ◽  
Neutral Selection ◽  
Erythrocyte Binding

scholarly journals Genetic diversity in two Plasmodium vivax protein ligands for reticulocyte invasion

2018 ◽  
Author(s):  
Camille Roesch ◽  
Jean Popovici ◽  
Sophalai Bin ◽  
Vorleak Run ◽  
Saorin Kim ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Vivax ◽  
Binding Protein ◽  
Invasion Pathways ◽  
Genomic Changes ◽  
Synonymous Mutations ◽  
Protein Ligands ◽  
Immune Pressure ◽  
Erythrocyte Binding ◽  
Duffy Negative

AbstractThe interaction between Plasmodium vivax Duffy binding protein (PvDBP) and Duffy antigen receptor for chemokines (DARC) has been described as critical for the invasion of human reticulocytes, although increasing reports of P. vivax infections in Duffy-negative individuals questions its unique role. To investigate the genetic diversity of the two main protein ligands for reticulocyte invasion, PvDBP and P. vivax Erythrocyte Binding Protein (PvEBP), we analyzed 458 isolates collected in Cambodia and Madagascar. First, we observed a high proportion of isolates with multiple copies PvEBP from Madagascar (56%) where Duffy negative and positive individuals coexist compared to Cambodia (19%) where Duffy-negative population is virtually absent. Whether the gene amplification observed is responsible for alternate invasion pathways remains to be tested. Second, we found that the PvEBP gene was less diverse than PvDBP gene (12 vs. 33 alleles) but provided evidence for an excess of nonsynonymous mutations with the complete absence of synonymous mutations. This finding reveals that PvEBP is under strong diversifying selection, and confirms the importance of this protein ligand in the invasion process of the human reticulocytes and as a target of acquired immunity. These observations highlight how genomic changes in parasite ligands improve the fitness of P. vivax isolates in the face of immune pressure and receptor polymorphisms.

scholarly journals Single-Chain Antibody Fragment Specific for Plasmodium vivax Duffy Binding Protein

2007 ◽  
Vol 14 (6) ◽  
pp. 726-731 ◽  
Author(s):  
So-Hee Kim ◽  
Seung-Young Hwang ◽  
Yong-Seok Lee ◽  
In-Hak Choi ◽  
Sae-Gwang Park ◽  
...  
Keyword(s):  
Phage Display ◽  
Plasmodium Vivax ◽  
Binding Protein ◽  
Antibody Fragment ◽  
Neutralizing Antibody ◽  
Active Immunization ◽  
Single Chain ◽  
Single Chain Antibody ◽  
Duffy Binding Protein ◽  
Erythrocyte Binding

ABSTRACT Phage display of single-chain variable fragment (scFv) antibodies is a powerful tool for selecting important, useful, and specific human antibodies. We constructed a library from three patients infected with Plasmodium vivax. Panning on recombinant PvRII enriched a population of scFvs that recognized region II of the P. vivax Duffy binding protein (DBP). Three clones of scFvs that reacted with PvRII were selected, and their biological functions were analyzed. These scFvs inhibited erythrocyte binding to DBP. Clone SFDBII92 had the greatest affinity (dissociation constant = 3.62 × 10−8 M) and the greatest inhibition activity (50% inhibitory concentration ≈ 2.9 μg/ml) to DBP. Thus, we demonstrated that human neutralizing antibody could be made from malaria patients using phage display and that these neutralizing scFvs should prove valuable for developing both passive and active immunization strategies based on DBP.

scholarly journals Mapping Epitopes of the Plasmodium vivax Duffy Binding Protein with Naturally Acquired Inhibitory Antibodies

2009 ◽  
Vol 78 (3) ◽  
pp. 1089-1095 ◽  
Author(s):  
Patchanee Chootong ◽  
Francis B. Ntumngia ◽  
Kelley M. VanBuskirk ◽  
Jia Xainli ◽  
Jennifer L. Cole-Tobian ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Binding Protein ◽  
High Titer ◽  
Blood Stage ◽  
Duffy Binding Protein ◽  
Linear Peptide ◽  
Binding Function ◽  
Blood Stage Infection ◽  
Erythrocyte Binding ◽  
Linear Epitopes

ABSTRACT Plasmodium vivax Duffy binding protein (DBP) is a merozoite microneme ligand vital for blood-stage infection, which makes it an important candidate vaccine for antibody-mediated immunity against vivax malaria. A differential screen with a linear peptide array compared the reactivities of noninhibitory and inhibitory high-titer human immune sera to identify target epitopes associated with protective immunity. Naturally acquired anti-DBP-specific serologic responses observed in the residents of a region of Papua New Guinea where P. vivax is highly endemic exhibited significant changes in DBP-specific titers over time. The anti-DBP functional inhibition for each serum ranged from complete inhibition to no inhibition even for high-titer responders to the DBP, indicating that epitope specificity is important. Inhibitory immune human antibodies identified specific B-cell linear epitopes on the DBP (SalI) ligand domain that showed significant correlations with inhibitory responses. Affinity-purified naturally acquired antibodies on these epitopes inhibited the DBP erythrocyte binding function greatly, confirming the protective value of specific epitopes. These results represent an important advance in our understanding of part of blood-stage immunity to P. vivax and some of the specific targets for vaccine-elicited antibody protection.

scholarly journals Genetic Diversity in New Members of the Reticulocyte Binding Protein Family in Thai Plasmodium vivax Isolates

PLoS ONE ◽  
2012 ◽  
Vol 7 (3) ◽  
pp. e32105 ◽  
Author(s):  
Varakorn Kosaisavee ◽  
Usa Lek-Uthai ◽  
Rossarin Suwanarusk ◽  
Anne Charlotte Grüner ◽  
Bruce Russell ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Vivax ◽  
Binding Protein ◽  
Protein Family ◽  
New Members

scholarly journals Correction: Genetic Diversity in New Members of the Reticulocyte Binding Protein Family in Thai Plasmodium vivax Isolates

PLoS ONE ◽  
2012 ◽  
Vol 7 (6) ◽  
Author(s):  
Varakorn Kosaisavee ◽  
Usa Lek-Uthai ◽  
Rossarin Suwanarusk ◽  
Anne Charlotte Grüner ◽  
Bruce Russell ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Vivax ◽  
Binding Protein ◽  
Protein Family ◽  
New Members

scholarly journals Genetic diversity, natural selection and haplotype grouping of Plasmodium vivax Duffy-binding protein genes from eastern and western Myanmar borders

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Yubing Hu ◽  
Lin Wang ◽  
Huguette Gaelle Ngassa Mbenda ◽  
Myat Thu Soe ◽  
Chunyun Yu ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Natural Selection ◽  
Genetic Differentiation ◽  
Plasmodium Vivax ◽  
Binding Protein ◽  
Duffy Binding Protein ◽  
High Genetic Diversity ◽  
Low Level ◽  
Malaria Epidemiology ◽  
Greater Mekong Subregion

Abstract Background Merozoite proteins of the malaria parasites involved in the invasion of red blood cells are selected by host immunity and their diversity is greatly influenced by changes in malaria epidemiology. In the Greater Mekong Subregion (GMS), malaria transmission is concentrated along the international borders and there have been major changes in malaria epidemiology with Plasmodium vivax becoming the dominant species in many regions. Here, we aimed to evaluate the genetic diversity of P. vivax Duffy-binding protein gene domain II (pvdbp-II) in isolates from the eastern and western borders of Myanmar, and compared it with that from global P. vivax populations. Methods pvdbp-II sequences were obtained from 85 and 82 clinical P. vivax isolates from the eastern and western Myanmar borders, respectively. In addition, 504 pvdbp-II sequences from nine P. vivax populations of the world were retrieved from GenBank and used for comparative analysis of genetic diversity, recombination and population structure of the parasite population. Results The nucleotide diversity of the pvdbp-II sequences from the Myanmar border parasite isolates was not uniform, with the highest diversity located between nucleotides 1078 and 1332. Western Myanmar isolates had a unique R391C mutation. Evidence of positive natural selection was detected in pvdbp-II gene in P. vivax isolates from the eastern Myanmar area. P. vivax parasite populations in the GMS, including those from the eastern, western, and central Myanmar as well as Thailand showed low-level genetic differentiation (FST, 0.000–0.099). Population genetic structure analysis of the pvdbp-II sequences showed a division of the GMS populations into four genetic clusters. A total of 60 PvDBP-II haplotypes were identified in 210 sequences from the GMS populations. Among the epitopes in PvDBP-II, high genetic diversity was found in epitopes 45 (379-SIFGT(D/G)(E/K)(K/N)AQQ(R/H)(R/C)KQ-393, π = 0.029) and Ia (416-G(N/K)F(I/M)WICK(L/I)-424], Ib [482-KSYD(Q/E)WITR-490, π = 0.028) in P. vivax populations from the eastern and western borders of Myanmar. Conclusions The pvdbp-II gene is genetically diverse in the eastern and western Myanmar border P. vivax populations. Positive natural selection and recombination occurred in pvdbp-II gene. Low-level genetic differentiation was identified, suggesting extensive gene flow of the P. vivax populations in the GMS. These results can help understand the evolution of the P. vivax populations in the course of regional malaria elimination and guide the design of PvDBP-II-based vaccine.

Genetic diversity and natural selection of Duffy binding protein of Plasmodium vivax Korean isolates

Acta Tropica ◽  
2013 ◽  
Vol 125 (1) ◽  
pp. 67-74 ◽  
Author(s):  
Hye-Lim Ju ◽  
Jung-Mi Kang ◽  
Sung-Ung Moon ◽  
Young-Yil Bahk ◽  
Pyo-Yun Cho ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Natural Selection ◽  
Plasmodium Vivax ◽  
Binding Protein ◽  
Duffy Binding Protein ◽  
Selection Of

scholarly journals Genetic Diversity of Plasmodium vivax Reticulocyte Binding Protein 2b in Global Parasite Populations

2021 ◽  
Author(s):  
xuexing zhang ◽  
Haichao Wei ◽  
Yangminghui Zhang ◽  
Yan Zhao ◽  
Lin Wang ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Vivax ◽  
Vaccine Development ◽  
Balancing Selection ◽  
Binding Protein ◽  
Critical Role ◽  
Binding Region ◽  
Geographical Separation ◽  
Antibody Titers ◽  
Parasite Populations

Abstract BackgroundPlasmodium vivax reticulocyte binding protein 2b (PvRBP2b) plays a critical role in parasite invasion of reticulocytes by binding the transferring receptor 1. PvRBP2b is a vaccine candidate since the antibody titers against PvRBP2b recombinant proteins are negatively correlated with the parasitemia and risk of vivax malaria. This study aims to analyze the genetic diversity of the PvRBP2b gene in the global P. vivax populations. MethodsThe near full-length PvRBP2b nucleotide sequences (190-8349 bp) were obtained from 88 P. vivax isolates collected from the China–Myanmar border (n=44) and Thailand (n=44). Additional 224 sequences of PvRBP2b were retrieved from genome sequences from the global parasite populations. The genetic diversity, neutral selections, haplotypes distribution and genetic differentiation of PvRBP2b were examined. ResultsThe genetic diversity of PvRBP2b was distributed unevenly with the peak in the reticulocyte binding region in the N-terminus and subjected to the balancing selection. Several amino acid variants were found in all or nearly all endemic fields. However, the critical residues responsible for reticulocyte binding were highly conserved. There was substantial population differentiation according to the geographical separation. The distribution of haplotypes in the reticulocyte binding region varied among regions; even the two major haplotypes Hap_6 and Hap_8 were found in only five populations. ConclusionsOur data showed considerable genetic variations of PvRBPb in global parasite populations, and the geographic divergence may pose a challenge to PvRBP2b-based vaccine development.

scholarly journals Design and Immunogenicity of a Novel Synthetic Antigen Based on the Ligand Domain of the Plasmodium vivax Duffy Binding Protein

2011 ◽  
Vol 19 (1) ◽  
pp. 30-36 ◽  
Author(s):  
Francis B. Ntumngia ◽  
John H. Adams
Keyword(s):  
Amino Acids ◽  
Plasmodium Vivax ◽  
Binding Protein ◽  
Cell Epitope ◽  
Binding Motif ◽  
Duffy Binding Protein ◽  
Asexual Blood Stage ◽  
Content Type ◽  
Specific Immunity ◽  
Erythrocyte Binding

ABSTRACTThe Duffy binding protein is considered a leading vaccine candidate against asexual blood-stagePlasmodium vivax. The interaction ofP. vivaxmerozoites with human reticulocytes through Duffy binding protein (DBP) and its cognate receptor is vital for parasite infection. The ligand domain of DBP (DBPII) is polymorphic, showing a diversity characteristic of selective immune pressure that tends to compromise vaccine efficacy associated with strain-specific immunity. A previous study resolved that a polymorphic region of DBPII was a dominant B-cell epitope target of human inhibitory anti-DBP antibodies, which we refer to as the DEK epitope for the amino acids in the SalI allele. We hypothesized that the polymorphic residues, which are not functionally important for erythrocyte binding but flank the receptor binding motif of DBPII, comprise variant epitopes that tend to divert the immune response away from more conserved epitopes. In this study, we designed, expressed, and evaluated the immunogenicity of a novel artificial DBPII allele, termed DEKnull, having nonpolar amino acids in the naturally occurring polymorphic charged residues of the DEK epitope. The DEKnull antigen retained erythrocyte-binding activity and elicited antibodies to shared epitopes of SalI DBPII from which it was derived. Our results confirmed that removal of the dominant variant epitope in the DEKnull vaccine lowered immunogenicity of DBPII, but inhibitory anti-DBPII antibodies were elicited against shared neutralizing epitopes on SalI. Focusing immune responses toward more conserved DBP epitopes may avoid development of a strain-specific immunity and enhance functional inhibition against broader range of DBPII variants.

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