Polymorphism patterns in Duffy-binding protein among Thai Plasmodium vivax isolates

Gosi, Panita; Khusmith, Srisin; Khalambaheti, Thareerat; Lanar, David E.; Schaecher, Kurt E.; Fukuda, Mark M.; Miller, Scott R.

doi:10.1186/1475-2875-7-112

Cited by 41 publications

(60 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The remaining two glycan variants were designed to shield polymorphic residues in PvDBP but retain exposure of proposed interaction surfaces for DARC binding and/or PvDBP dimerization (Figures 1 and 2). There are at least 36 polymorphic positions in PvDBPII [28], [29], but many sequence variants are extremely rare (Figure S2). The majority of polymorphic residues are dimorphic and localized to subdomain 2 (Figure 2).…”

Section: Resultsmentioning

confidence: 99%

“…P. vivax dependence on DARC for invasion and its restrictive preference for reticulocytes supports PvDBP vaccine development. However, the rapid kinetics of parasite invasion (less than one minute) [26], [27] combined with PvDBP polymorphism [28], [29] pose challenges for vaccine development that may be addressable by the rational redesign of PvDBPII for improved immunogenic properties.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Glycan Masking of Plasmodium vivax Duffy Binding Protein for Probing Protein Binding Function and Vaccine Development

et al. 2013

View full text Add to dashboard Cite

Glycan masking is an emerging vaccine design strategy to focus antibody responses to specific epitopes, but it has mostly been evaluated on the already heavily glycosylated HIV gp120 envelope glycoprotein. Here this approach was used to investigate the binding interaction of Plasmodium vivax Duffy Binding Protein (PvDBP) and the Duffy Antigen Receptor for Chemokines (DARC) and to evaluate if glycan-masked PvDBPII immunogens would focus the antibody response on key interaction surfaces. Four variants of PVDBPII were generated and probed for function and immunogenicity. Whereas two PvDBPII glycosylation variants with increased glycan surface coverage distant from predicted interaction sites had equivalent binding activity to wild-type protein, one of them elicited slightly better DARC-binding-inhibitory activity than wild-type immunogen. Conversely, the addition of an N-glycosylation site adjacent to a predicted PvDBP interaction site both abolished its interaction with DARC and resulted in weaker inhibitory antibody responses. PvDBP is composed of three subdomains and is thought to function as a dimer; a meta-analysis of published PvDBP mutants and the new DBPII glycosylation variants indicates that critical DARC binding residues are concentrated at the dimer interface and along a relatively flat surface spanning portions of two subdomains. Our findings suggest that DARC-binding-inhibitory antibody epitope(s) lie close to the predicted DARC interaction site, and that addition of N-glycan sites distant from this site may augment inhibitory antibodies. Thus, glycan resurfacing is an attractive and feasible tool to investigate protein structure-function, and glycan-masked PvDBPII immunogens might contribute to P. vivax vaccine development.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Glycan Masking of Plasmodium vivax Duffy Binding Protein for Probing Protein Binding Function and Vaccine Development

et al. 2013

View full text Add to dashboard Cite

show abstract

“…H1.T1, H3.T1, H3.T2, H3.T3 and M3.T1 epitopes are the variant strain among Thai vivax isolates [19]. NI is the target epitopes of non-inhibitory antibodies.…”

Section: Methodsmentioning

confidence: 99%

“…The highest frequency of polymorphism was found in residues D384G, R390H, L424I, W437R and I503K [19]. The phylogenetic analysis of dbpII Thai P. vivax isolates demonstrated that most Thai isolates shared distinct alleles with P. vivax isolates from different geographical areas with some allele groups so far unique to Thailand [19]. Since DBPII polymorphisms among Thai isolates are extensive and some are unique, understanding naturally protective antibody against DBPII needs to be defined.…”

Section: Introductionmentioning

confidence: 99%

Characterization of Inhibitory Anti-Duffy Binding Protein II Immunity: Approach to Plasmodium vivax Vaccine Development in Thailand

et al. 2012

View full text Add to dashboard Cite

Plasmodium vivax Duffy binding protein region II (DBPII) is an important vaccine candidate for antibody-mediated immunity against vivax malaria. A significant challenge for vaccine development of DBPII is its highly polymorphic nature that alters sensitivity to neutralizing antibody responses. Here, we aim to characterize naturally-acquired neutralizing antibodies against DBPII in individual Thai residents to give insight into P. vivax vaccine development in Thailand. Anti-DBPII IgG significantly increased in acute vivax infections compared to uninfected residents and naive controls. Antibody titers and functional anti-DBPII inhibition varied widely and there was no association between titer and inhibition activity. Most high titer plasmas had only a moderate to no functional inhibitory effect on DBP binding to erythrocytes, indicating the protective immunity against DBPII binding is strain specific. Only 5 of 54 samples were highly inhibitory against DBP erythrocyte-binding function. Previously identified target epitopes of inhibitory anti-DBPPII IgG (H1, H2 and H3) were localized to the dimer interface that forms the DARC binding pocket. Amino acid polymorphisms (monomorphic or dimorphic) in H1 and H3 protective epitopes change sensitivity of immune inhibition by alteration of neutralizing antibody recognition. The present study indicates Thai variant H1.T1 (R308S), H3.T1 (D384G) and H3.T3 (K386N) are the most important variants for a DBPII candidate vaccine needed to protect P. vivax in Thai residents.

show abstract

“…Numerous and widespread polymorphisms have been identified in Plasmodium invasion ligands, specifically PfEBA-175 and Plasmodium vivax Duffy-binding protein (PvDBP) (17)(18)(19). In contrast, only four polymorphic mutants have been identified in RII PfEBA-140, all of which are present in the F1 domain: I185V, N239S, K261R/K261T, and K285E (11).…”

mentioning

confidence: 99%

Molecular Basis for Sialic Acid-dependent Receptor Recognition by the Plasmodium falciparum Invasion Protein Erythrocyte-binding Antigen-140/BAEBL

Malpede¹,

Lin²,

Tolia

2013

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: PfEBA-140 recognizes sialic acid on its receptor glycophorin C during erythrocyte invasion. Results: PfEBA-140 contains two sialic acid-binding pockets distinct from other sialic acid-binding proteins and with divergent roles in receptor recognition. Conclusion:The glycan-binding pockets define receptor recognition, specificity, and putative switching. Significance: This study provides the first detailed molecular view of receptor recognition by a critical P. falciparum invasion ligand.

show abstract

Polymorphism patterns in Duffy-binding protein among Thai Plasmodium vivax isolates

Cited by 41 publications

References 26 publications

Glycan Masking of Plasmodium vivax Duffy Binding Protein for Probing Protein Binding Function and Vaccine Development

Glycan Masking of Plasmodium vivax Duffy Binding Protein for Probing Protein Binding Function and Vaccine Development

Characterization of Inhibitory Anti-Duffy Binding Protein II Immunity: Approach to Plasmodium vivax Vaccine Development in Thailand

Molecular Basis for Sialic Acid-dependent Receptor Recognition by the Plasmodium falciparum Invasion Protein Erythrocyte-binding Antigen-140/BAEBL

Contact Info

Product

Resources

About