Mapping Epitopes of the Plasmodium vivax Duffy Binding Protein with Naturally Acquired Inhibitory Antibodies
Open Access
- 1 March 2010
- journal article
- research article
- Published by American Society for Microbiology in Infection and Immunity
- Vol. 78 (3) , 1089-1095
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.Keywords
This publication has 29 references indexed in Scilit:
- Naturally acquired Duffy-binding protein-specific binding inhibitory antibodies confer protection from blood-stage Plasmodium vivax infectionProceedings of the National Academy of Sciences, 2008
- Structural Insight into Epitopes in the Pregnancy-Associated Malaria Protein VAR2CSAPLOS Pathogens, 2008
- Plasmodium vivax Invasion of Human Erythrocytes Inhibited by Antibodies Directed against the Duffy Binding ProteinPLOS Medicine, 2007
- Structural Basis for the EBA-175 Erythrocyte Invasion Pathway of the Malaria Parasite Plasmodium falciparumCell, 2005
- Sulphated tyrosines mediate association of chemokines and Plasmodium vivax Duffy binding protein with the Duffy antigen/receptor for chemokines (DARC)Molecular Microbiology, 2005
- Age‐Acquired Immunity to aPlasmodium vivaxInvasion Ligand, the Duffy Binding ProteinThe Journal of Infectious Diseases, 2002
- Acquisition and Decay of Antibodies to Pregnancy‐Associated Variant Antigens on the Surface ofPlasmodium falciparum–Infected Erythrocytes That Protect against Placental ParasitemiaThe Journal of Infectious Diseases, 2001
- Analysis of polymorphic regions of Plasmodium vivax Duffy binding protein of Korean isolatesThe Korean Journal of Parasitology, 2001
- Assessment of different sources of variation in the antibody responses to specific malaria antigens in children in Papua New GuineaInternational Journal of Epidemiology, 2000
- The duffy receptor family of plasmodium knowlesi is located within the micronemes of invasive malaria merozoitesCell, 1990