title: Immunogenicity of a synthetic vaccine based on Plasmodium vivax Duffy binding protein region II.
abstract: Molecules that play a role in Plasmodium merozoite invasion of host red blood cells represent attractive targets for blood-stage vaccine development against malaria. In Plasmodium vivax, merozoite invasion of reticulocytes is mediated by the Duffy binding protein (DBP), which interacts with its cognate receptor, the Duffy antigen receptor for chemokines, on the surface of reticulocytes. The DBP ligand domain, known as region II (DBPII), contains the critical residues for receptor recognition, making it a prime target for vaccine development against blood-stage vivax malaria. In natural infections, DBP is weakly immunogenic and DBPII allelic variation is associated with strain-specific immunity, which may compromise vaccine efficacy. In a previous study, a synthetic vaccine termed DEKnull that lacked an immunodominant variant epitope in DBPII induced functional antibodies to shared neutralizing epitopes on the native Sal1 allele. Anti-DEKnull antibody titers were lower than anti-Sal1 titers but produced more consistent, strain-transcending anti-DBPII inhibitory responses. In this study, we further characterized the immunogenicity of DEKnull, finding that immunization with recombinant DEKnull produced an immune response comparable to that obtained with native recombinant DBP alleles. Further investigation of DEKnull is necessary to enhance its immunogenicity and broaden its specificity.
authors: Global Health Infectious Disease Research Program, Department of Global Health, University of South Florida, Tampa, Florida, USA.
authors: Francis B
authors: FB
authors: Ntumngia
authors: Global Health Infectious Disease Research Program, Department of Global Health, University of South Florida, Tampa, Florida, USA.
authors: Samantha J
authors: SJ
authors: Barnes
authors: Global Health Infectious Disease Research Program, Department of Global Health, University of South Florida, Tampa, Florida, USA.
authors: Amy M
authors: AM
authors: McHenry
authors: Global Health Infectious Disease Research Program, Department of Global Health, University of South Florida, Tampa, Florida, USA.
authors: Miriam T
authors: MT
authors: George
authors: Global Health Infectious Disease Research Program, Department of Global Health, University of South Florida, Tampa, Florida, USA.
authors: Jesse
authors: J
authors: Schloegel
authors: Global Health Infectious Disease Research Program, Department of Global Health, University of South Florida, Tampa, Florida, USA usfmalaria@gmail.com.
authors: John H
authors: JH
authors: Adams
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D049109:Cell Proliferation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008288:Malaria / Q000469:parasitology / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D008807:Mice, Inbred BALB C; D010966:Plasmodium vivax / Q000235:genetics / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000276:immunology; D016896:Treatment Outcome; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; C066001:Duffy antigen binding protein, Plasmodium; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic