# US 8,784,832 B2 · Synthetic antigen based on the ligand domain of the Plasmodium vivax duffy binding protein > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 8,784,832 B2 - Document ID: US8784832B2 - Status: Granted - Kind: B2 - Application number: 13/589,253 - Filed: 2012-08-20 - Published: 2013-02-21 - Granted: 2014-07-22 - Earliest claimed: 2011-08-19 - Assignees: University of South Florida (A Florida Non-Profit Corporation) - Applicants: John H. Adams; Francis B. Ntumngia; Jesse L. Schloegel; Samantha J. Barnes; Amy M. McHenry; Patchanee Chootong - Inventors: John H. Adams; Francis B. Ntumngia; Jesse L. Schloegel; Samantha J. Barnes; Amy M. McHenry; Patchanee Chootong - Web page: https://patentgrep.com/patent/US8784832B2 ## CPC - C07K 14/445: Plasmodium - A61K 39/015: Hemosporidia antigens, e.g. Plasmodium antigens - A61P 33/02: Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis - A61P 37/04: Immunostimulants - Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE ## 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. ## Claims ### Claim 1 An engineered Plasmodium vivax Duffy Binding Protein (PvDBPII) having a modified dominant immunogenic polymorphic B-cell epitope region, wherein the 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 engineered PvDBPII can generate in a recipient animal or human subject an immune response having 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. ### Claim 2 (depends on 1) The engineered P. vivax Duffy Binding Protein (PvDBPII) of claim 1, wherein the modified region of the engineered PvDBPII consists essentially of the amino acid sequence SEQ ID NO: 4 (ASTAATSRTS). ### Claim 3 (depends on 1) The engineered P. vivax Duffy Binding Protein (PvDBPII) of claim 1, having the amino sequence at least 95% sequence identity with the sequence SEQ ID NO: 2. ### Claim 4 (depends on 1) The engineered P. vivax Duffy Binding Protein (PvDBPII) of claim 1, wherein the engineered PvDBPII is expressed from a recombinant nucleic acid inserted into an expression vector. ### Claim 5 (depends on 4) The engineered P. vivax Duffy Binding Protein (PvDBPII) of claim 4, wherein the recombinant nucleic acid is codon optimized for expression of the PvDBPII in a genetically modified host cell. ### Claim 6 A composition formulated for the generation in a recipient animal or human of an immune response, the composition comprising an engineered Plasmodium vivax Duffy Binding Protein (PvDBPII) having a modified dominant immunogenic polymorphic B-cell epitope region, wherein the 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 having the amino acid sequence SEQ ID NO: 3 (DEKAQQRRKQWWNESK) and wherein the engineered PvDBPII can generate in a recipient animal or human subject an immune response having 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 variant, and further comprising a pharmaceutically acceptable carrier. ### Claim 7 (depends on 6) The composition of claim 6, wherein the modified region of the engineered PvDBPII consists essentially of the amino acid sequence SEQ ID NO: 4 (ASTAATSRTS). ### Claim 8 (depends on 6) The composition of claim 6, wherein the engineered PvDBPII has an amino sequence having at least 95% sequence identity with the sequence SEQ ID NO: 2. ### Claim 9 (depends on 6) The composition of claim 6, wherein the engineered PvDBPII is expressed from a recombinant nucleic acid inserted into an expression vector. ### Claim 10 (depends on 9) The composition of claim 9, wherein the recombinant nucleic acid is codon optimized for expression of the PvDBPII in a genetically modified host cell. ### Claim 11 (depends on 1) The engineered P. vivax Duffy Binding Protein (PvDBPII) of claim 1, having the amino sequence SEQ ID NO: 2. ### Claim 12 (depends on 6) The composition of claim 6, wherein the engineered PvDBPII has the amino sequence SEQ ID NO: 2.