Synthetic antigen based on the ligand domain of the Plasmodium vivax duffy binding protein

US8784832B2 · kind B2 · utility

Assignee

• University of South Florida (A Florida Non-Profit Corporation) · US

Inventors

• John H. Adams · Tampa, US
• Francis B. Ntumngia · Tampa, US
• Jesse L. Schloegel · Sydney, AU
• Samantha Jones Barnes · Tampa, US
• Amy M. McHenry · Cleburne, US
• Patchanee Chootong · Bangkok, TH

Key dates

• Filing date: Aug 20, 2012
• Grant date: Jul 22, 2014
• Expiry date: Aug 20, 2032

Classification

• Technology area (CPC Y): Emerging Cross-Sectional Technologies
• CPC primary: Y02A50/30
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

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.