Frequent expansion of Plasmodium vivax Duffy Binding Protein in Ethiopia and its epidemiological significance

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.

Download Full-text

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

Infection and Immunity ◽

10.1128/iai.01036-09 ◽

2009 ◽

Vol 78 (3) ◽

pp. 1089-1095 ◽

Cited By ~ 64

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.

Download Full-text

Persistence of Long-lived Memory B Cells specific to Duffy Binding Protein in individuals exposed to Plasmodium vivax

Scientific Reports ◽

10.1038/s41598-018-26677-x ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 10

Author(s):

Siriruk Changrob ◽

Amy M. McHenry ◽

Myat Htut Nyunt ◽

Jetsumon Sattabongkot ◽

Eun-Taek Han ◽

...

Keyword(s):

B Cells ◽

Plasmodium Vivax ◽

Binding Protein ◽

Memory B Cells ◽

Duffy Binding Protein

Download Full-text

DARC extracellular domain remodeling in maturating reticulocytes explains Plasmodium vivax tropism

Blood ◽

10.1182/blood-2017-03-774364 ◽

2017 ◽

Vol 130 (12) ◽

pp. 1441-1444 ◽

Cited By ~ 23

Author(s):

Elina Ovchynnikova ◽

Francesca Aglialoro ◽

Arthur E. H. Bentlage ◽

Gestur Vidarsson ◽

Nichole D. Salinas ◽

...

Keyword(s):

Binding Site ◽

Plasmodium Vivax ◽

Binding Protein ◽

Extracellular Domain ◽

Small Population ◽

Duffy Binding Protein ◽

Key Points

Key Points P vivax Duffy binding protein associates exclusively with a small population of immature reticulocytes. Increased DARC-DBP binding site accessibility in immature reticulocytes compared with erythrocytes is a key to infection by P vivax.

Download Full-text