title: C3d-defined complement receptor-binding peptide p28 conjugated to circumsporozoite protein provides protection against Plasmodium berghei.
abstract: Immune response against circumsporozoite protein (CSP) of Plasmodium berghei, a major surface protein on the sporozoite, confers protection in various murine malaria models. Engineered DNA vaccine encoding CSP and 3 copies of C3d caused an unexpected loss in protection attributed to the binding of C3d to the C-terminal region of CSP. Because the C3d region known as p28 represents the complement receptor (CR) 2-binding motif, we developed a CSP-3 copies of p28 DNA construct (CSP-3p28). CSP-3p28-immunized mice were better protected against P. berghei sporozoites than CSP-immunized mice 6 weeks after the 2nd boost, produced sufficient IgG1 anti-CSP and CSP C-terminus antibody and failed to produce IgG2a. CSP-3C3d-immunized mice were not protected, failed to produce IgG1 and produced high amounts of IgG2a. We conclude that use of the CR2-binding motif of C3d as molecular adjuvant to CSP results in anti-malaria protective immune response probably by targeting the chimeric protein to CR2.
authors.affiliation: Division of Malaria Vaccine Development, Walter Reed Army Institute of Research, Silver Spring, MD 20910, United States. elke.bergmannleitner@us.army.mil
authors.forename: Elke S
authors.initials: ES
authors.lastname: Bergmann-Leitner
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Duncan
authors.forename: Wolfgang W
authors.initials: WW
authors.lastname: Leitner
authors.forename: Albert
authors.initials: A
authors.lastname: Neutzner
authors.forename: Tatyana
authors.initials: T
authors.lastname: Savranskaya
authors.forename: Evelina
authors.initials: E
authors.lastname: Angov
authors.forename: George C
authors.initials: GC
authors.lastname: Tsokos
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D015933:Complement C3d / Q000378:metabolism*; D008288:Malaria / Q000276:immunology* / Q000517:prevention & control; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000276:immunology; D010962:Plasmodium berghei / Q000276:immunology*; D015800:Protozoan Proteins / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D034101:Sporozoites
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D010446:Peptide Fragments; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; C041595:circumsporozoite protein, Protozoan; D015933:Complement C3d