Age‐Acquired Immunity to a<i>Plasmodium vivax</i>Invasion Ligand, the Duffy Binding Protein

Cole-Tobian, Jennifer L.; Cortés, Alfred; Baisor, Moses; Kastens, Will; Jia, Xiaoyun; Bockarie, Moses J.; Adams, John; King, Christopher L.

doi:10.1086/341776

Cited by 74 publications

(99 citation statements)

References 37 publications

(48 reference statements)

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“…These epitopes are predicted to be exposed to the surface of the PvDBP molecule [30]. The putative changes in protein structure may alter antibody binding efficacy of a particular epitope, thereby allowing escape from the host protective immune response [13,30]. …”

Section: Discussionmentioning

confidence: 99%

“…Critical binding motifs in PvDBPII have been mapped to a 170 amino acid stretch (amino acids 291-460), which includes cysteines 5-8 [11,12]. PvDBPII shows the highest genetic diversity compared to the remaining PvDBP regions and appears to be under strong selective pressure [13,14]. Analysis of genetic variation of PvDBPII among P. vivax field isolates from different geographical regions, including Brazil, Colombia, South Korea, Papua New Guinea, Thailand, showed that the PvDBPII is highly polymorphic, but the cysteine residues are conserved within and between P. vivax populations from different geographic regions [14-21].…”

Section: Introductionmentioning

confidence: 99%

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Genetic polymorphism and natural selection of Duffy binding protein of Plasmodium vivax Myanmar isolates

Kang

Moon

Kim

et al. 2012

Malar J

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BackgroundPlasmodium vivax Duffy binding protein (PvDBP) plays an essential role in erythrocyte invasion and a potential asexual blood stage vaccine candidate antigen against P. vivax. The polymorphic nature of PvDBP, particularly amino terminal cysteine-rich region (PvDBPII), represents a major impediment to the successful design of a protective vaccine against vivax malaria. In this study, the genetic polymorphism and natural selection at PvDBPII among Myanmar P. vivax isolates were analysed.MethodsFifty-four P. vivax infected blood samples collected from patients in Myanmar were used. The region flanking PvDBPII was amplified by PCR, cloned into Escherichia coli, and sequenced. The polymorphic characters and natural selection of the region were analysed using the DnaSP and MEGA4 programs.ResultsThirty-two point mutations (28 non-synonymous and four synonymous mutations) were identified in PvDBPII among the Myanmar P. vivax isolates. Sequence analyses revealed that 12 different PvDBPII haplotypes were identified in Myanmar P. vivax isolates and that the region has evolved under positive natural selection. High selective pressure preferentially acted on regions identified as B- and T-cell epitopes of PvDBPII. Recombination may also be played a role in the resulting genetic diversity of PvDBPII.ConclusionsPvDBPII of Myanmar P. vivax isolates displays a high level of genetic polymorphism and is under selective pressure. Myanmar P. vivax isolates share distinct types of PvDBPII alleles that are different from those of other geographical areas. These results will be useful for understanding the nature of the P. vivax population in Myanmar and for development of PvDBPII-based vaccine.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Genetic polymorphism and natural selection of Duffy binding protein of Plasmodium vivax Myanmar isolates

Kang

Moon

Kim

et al. 2012

Malar J

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“…16,[18][19][20] After natural exposure to P. vivax infection, individuals residing in malaria-endemic areas develop antibodies that block binding of DBP to DARC-positive erythrocytes. 21 It has been hypothesized that polymorphisms in PvDBP-II arose from immune selection 16,[18][19][20][21][22] so that the frequency of nonsynonymous mutations exceeds that of synonymous mutations in PvDBP-II. These polymorphic regions represent B-and/or T-cell epitopes recognized by the host immune response that might inhibit protective immunity against DBP.…”

Section: Introductionmentioning

confidence: 99%

“…29 In addition, different studies suggested that stronger humoral and cellular immune responses to PvDBP-II develop progressively with increasing age, 22,24,29,30 showing a boosting effect that was likely because of repeated exposures to the infection. 28 Also, the anti-PvDBP-II antibodies in populations living in areas endemic for P. vivax could block PvDBP-II ligand DARC-positive erythrocytes 21,31 and inhibit erythrocyte invasion in vitro .…”

Section: Introductionmentioning

confidence: 99%

Antibody Responses and Avidity of Naturally Acquired Anti-Plasmodium vivax Duffy Binding Protein (PvDBP) Antibodies in Individuals from an Area with Unstable Malaria Transmission

Zakeri

Babaeekhou²,

Mehrizi³

et al. 2011

The American Society of Tropical Medicine and Hygiene

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Plasmodium vivax remains an important cause of morbidity outside Africa, and no effective vaccine is available against this parasite. The P. vivax Duffy binding protein (PvDBP) is essential during merozoite invasion into erythrocytes, and it is a target for protective immunity against malaria. This investigation was designed to evaluate naturally acquired antibodies to two variant forms of PvDBP-II antigen (DBP-I and -VI) in malaria individuals (N = 85; median = 22 years) who were living in hypoendemic areas in Iran. The two PvDBP-II variants were expressed in Escherichia coli, and immunoglobulin G (IgG) isotype composition and avidity of naturally acquired antibodies to these antigens were measured using enzyme-linked immunosorbent assay (ELISA). Results showed that almost 32% of the studied individuals had positive antibody responses to the two PvDBP-II variants, and the prevalence of responders did not differ significantly (P > 0.05; χ2 test). The IgG-positive samples exhibited 37.03% and 40.8% high-avidity antibodies for PvDBP-I and PvDBP-VI variants, respectively. Furthermore, high-avidity IgG1 antibody was found in 39.1% of positive sera for each examined variant antigen. The avidity of antibodies for both PvDBP variant antigens and the prevalence of responders with high- and intermediate-avidity IgG, IgG1, and IgG3 antibodies were similar in patients (P > 0.05; χ2 test). Moreover, the prevalence of IgG antibody responses to the two variants significantly increased with exposure and host age. To sum up, the results provided additional data in our understanding of blood-stage immunity to PvDBP, supporting the rational development of an effective blood-stage vaccine based on this antigen.

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“…Region II of DBP (DBPII) may be a critical target for host protective immunity, based on several observations. First, certain regions of DBPII are highly polymorphic (24,25) and appear to be maintained by immune selection (11). Second, antibodies to DBPII from populations in areas endemic for P. vivax inhibit binding of COS-7 cells that express DBPII ligand on their surface to DARC-positive erythrocytes (16,23).…”

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confidence: 99%

Epitope-Specific Humoral Immunity to Plasmodium vivax Duffy Binding Protein

et al. 2003

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Erythrocyte invasion by Plasmodium vivax is completely dependent on binding to the Duffy blood group antigen by the parasite Duffy binding protein (DBP). The receptor-binding domain of this protein lies within a cysteine-rich region referred to as region II (DBPII).To examine whether antibody responses to DBP correlate with age-acquired immunity to P. vivax, antibodies to recombinant DBP (rDBP) were measured in 551 individuals residing in a village endemic for P. vivax in Papua New Guinea, and linear epitopes mapped in the critical binding region of DBPII. Antibody levels to rDBP II increased with age. Four dominant linear epitopes were identified, and the number of linear epitopes recognized by semiimmune individuals increased with age, suggesting greater recognition with repeated infection. Some individuals had antibodies to rDBP II but not to the linear epitopes, indicating the presence of conformational epitopes. This occurred in younger individuals or subjects acutely infected for the first time with P. vivax, indicating that repeated infection is required for recognition of linear epitopes. All four dominant B-cell epitopes contained polymorphic residues, three of which showed variant-specific serologic responses in over 10% of subjects examined. In conclusion, these results demonstrate age-dependent and variant-specific antibody responses to DBPII and implicate this molecule in partial acquired immunity to P. vivax in populations in endemic areas.Plasmodium vivax malaria is widely distributed throughout the world and accounts for over half of all malaria infections outside of Africa and about 10% of malaria infections in Africa (15). The intraerythrocytic stage of the parasite in humans requires specific receptor-ligand interactions for successful invasion of its host (6). P. vivax invasion of erythrocytes is absolutely dependent on binding to the Duffy blood group. As a result, Duffy-negative individuals are completely resistant to P. vivax malaria (19). One member of a large family of erythrocyte binding proteins, referred to as the Duffy binding protein (DBP), mediates binding to the Duffy blood group or Duffy receptor for chemokines (DARC), since this Duffy blood group antigen has been identified to be a chemokine receptor (14). The critical binding motif of P. vivax DBP lies within a cysteine-rich domain referred to as region II between amino acids (aa) 291 and 460 (21). Region II of DBP (DBPII) may be a critical target for host protective immunity, based on several observations. First, certain regions of DBPII are highly polymorphic (24, 25) and appear to be maintained by immune selection (11). Second, antibodies to DBPII from populations in areas endemic for P. vivax inhibit binding of COS-7 cells that express DBPII ligand on their surface to DARC-positive erythrocytes (16, 23). Third, antibodies raised to region II of the Plasmodium knowlesi ␣ protein, a molecule that is 70% homologous to P. vivax DBP and also mediates DARC-dependent infection of human erythrocytes, can inhibit P. knowlesi invasio...

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Age‐Acquired Immunity to aPlasmodium vivaxInvasion Ligand, the Duffy Binding Protein

Cited by 74 publications

References 37 publications

Genetic polymorphism and natural selection of Duffy binding protein of Plasmodium vivax Myanmar isolates

Genetic polymorphism and natural selection of Duffy binding protein of Plasmodium vivax Myanmar isolates

Antibody Responses and Avidity of Naturally Acquired Anti-Plasmodium vivax Duffy Binding Protein (PvDBP) Antibodies in Individuals from an Area with Unstable Malaria Transmission

Epitope-Specific Humoral Immunity to Plasmodium vivax Duffy Binding Protein

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