Synthetic antigen based on the ligand domain of the plasmodium vivax duffy binding protein
The disclosure provides compositions that are useful for eliciting a strain-transcending immune response in an animal or human directed against the blood-stage of the malarial parasite Plasmodium vivax . The compositions are based on the ligand domain of Plasmodium vivax Duffy binding protein (PvDBPII). Polar charged polymorphic residues within the dominant strain-specific B-cell epitope were mutated to uncharged residues (e.g. serine, alanine and threonine). This DEKnull variant of PvDBPII produced in bacteria can be purified and refolded in vitro to mimic conformation and erythrocyte binding function of native DBPII. Immunogenicity of DEKnull was confirmed by administration to mice. Compared to the naturally-occurring, strain variant DBPII, DEKnull elicits antibodies that are more broadly reactive with different strain variants of DBPII and enhances production of functional inhibitory antibodies to the shared protective epitopes of native DBPII.
1. A method of eliciting in a subject an immune response, comprising administering to the subject an immunogenic composition comprising an engineered Plasmodium vivax Duffy Binding Protein (PvDBPII) comprising a modified region corresponding to an dominant immunogenic polymorphic B-cell epitope region of a native PvDBPII, wherein said modified region comprises the amino acid sequence SEQ ID NO: 4 (ASTAATSRTS), and wherein said modified region has reduced immunogenic dominance when compared to the region of a native PvDBPII comprising the amino acid sequence SEQ ID NO: 3 (DEKAQQRRKQWWNESK), and wherein the elicited immune response has increased binding specificity for conserved Duffy binding epitopes of a Plasmodium Duffy Binding Protein when compared to an immune response generated by a natural PvDBPII.
2. The method of claim 1 , wherein the immunogenic composition comprises the engineered PvDBPII and an immunoadjuvant.
3. The method of claim 1 , wherein the engineered PvDBPII has fewer polymorphic amino acids when compared to an dominant immunogenic polymorphic B-cell epitopic region of a native PvDBP.
4. The method of claim 1 , wherein the modified region of the engineered PvDBPII consists essentially of the amino acid sequence SEQ ID NO: 4 (ASTAATSRTS).
5. The method of claim 1 , wherein the engineered Plasmodium vivax Duffy Binding Protein comprises the amino sequence having at least 95% sequence identity with the sequence SEQ ID NO: 2.
6. The method of claim 1 , wherein the engineered Plasmodium vivax Duffy Binding Protein has the amino acid sequence SEQ ID NO: 2.