Conserved and variant epitopes of Plasmodium vivax Duffy binding protein as targets of inhibitory monoclonal antibodies.
The Duffy binding protein (DBP) is a vital ligand for Plasmodium vivax blood-stage merozoite invasion, making the molecule an attractive vaccine candidate against vivax malaria. Similar to other blood-stage vaccine candidates, DBP allelic variation eliciting a strain-specific immunity may be a major challenge for development of a broadly effective vaccine against vivax malaria. To understand whether conserved epitopes can be the target of neutralizing anti-DBP inhibition, we generated a set of monoclonal antibodies to DBP and functionally analyzed their reactivity to a panel of allelic variants. Quantitative analysis by enzyme-linked immunosorbent assay (ELISA) determined that some monoclonal antibodies reacted strongly with epitopes conserved on all DBP variants tested, while reactivity of others was allele specific. Qualitative analysis characterized by anti-DBP functional inhibition using an in vitro erythrocyte binding inhibition assay indicated that there was no consistent correlation between the endpoint titers and functional inhibition. Some monoclonal antibodies were broadly inhibitory while inhibition of others varied significantly by target allele. These data demonstrate a potential for vaccine-elicited immunization to target conserved epitopes but optimization of DBP epitope target specificity and immunogenicity may be necessary for protection against diverse P. vivax strains.
University of South Florida, Tampa, Florida, USA.
Francis B
FB
Ntumngia
Jesse
J
Schloegel
Samantha J
SJ
Barnes
Amy M
AM
McHenry
Sanjay
S
Singh
Christopher L
CL
King
John H
JH
Adams
D000911:Antibodies, Monoclonal / Q000276:immunology*; D057134:Antibodies, Neutralizing; D000940:Antigenic Variation; D000953:Antigens, Protozoan / Q000276:immunology*; D017124:Conserved Sequence; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D009500:Neutralization Tests; D010966:Plasmodium vivax / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000276:immunology*
D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000953:Antigens, Protozoan; C066001:Duffy antigen binding protein, Plasmodium; D000939:Epitopes; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface