Abstract

The Duffy binding protein is considered a leading vaccine candidate against asexual blood-stage Plasmodium vivax. The interaction of P. vivax merozoites with human reticulocytes through Duffy binding protein (DBP) and its cognate receptor is vital for parasite infection. The ligand domain of DBP (DBPII) is polymorphic, showing a diversity characteristic of selective immune pressure that tends to compromise vaccine efficacy associated with strain-specific immunity. A previous study resolved that a polymorphic region of DBPII was a dominant B-cell epitope target of human inhibitory anti-DBP antibodies, which we refer to as the DEK epitope for the amino acids in the SalI allele. We hypothesized that the polymorphic residues, which are not functionally important for erythrocyte binding but flank the receptor binding motif of DBPII, comprise variant epitopes that tend to divert the immune response away from more conserved epitopes. In this study, we designed, expressed, and evaluated the immunogenicity of a novel artificial DBPII allele, termed DEKnull, having nonpolar amino acids in the naturally occurring polymorphic charged residues of the DEK epitope. The DEKnull antigen retained erythrocyte-binding activity and elicited antibodies to shared epitopes of SalI DBPII from which it was derived. Our results confirmed that removal of the dominant variant epitope in the DEKnull vaccine lowered immunogenicity of DBPII, but inhibitory anti-DBPII antibodies were elicited against shared neutralizing epitopes on SalI. Focusing immune responses toward more conserved DBP epitopes may avoid development of a strain-specific immunity and enhance functional inhibition against broader range of DBPII variants.

Links

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Publisher Full Text

Authors

Ntumngia FB, Adams JH

Institution

Global Health Infectious Disease Research, Department of Global Health, College of Public Health, University of South Florida, Tampa, Florida, USA.

Source

Clinical and vaccine immunology : CVI 19:1 2012 Jan pg 30-6

MeSH

Amino Acid Sequence
Animals
Antibodies, Neutralizing
Antibodies, Protozoan
Antigens, Protozoan
Enzyme-Linked Immunosorbent Assay
Epitopes, B-Lymphocyte
Erythrocytes
Humans
Immunoblotting
Immunodominant Epitopes
Malaria Vaccines
Molecular Sequence Data
Plasmodium vivax
Protein Binding
Protozoan Proteins
Rats
Receptors, Cell Surface
Vaccines, Synthetic

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

22116684