C3d-defined complement receptor-binding peptide p28 conjugated to circumsporozoite protein provides protection against Plasmodium berghei.
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.
Bergmann-Leitner
Elke S
ES
Division of Malaria Vaccine Development, Walter Reed Army Institute of Research, Silver Spring, MD 20910, United States. elke.bergmannleitner@us.army.mil
Duncan
Elizabeth H
EH
Leitner
Wolfgang W
WW
Neutzner
Albert
A
Savranskaya
Tatyana
T
Angov
Evelina
E
Tsokos
George C
GC
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
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