The oligomerization domain of C4-binding protein (C4bp) acts as an adjuvant, and the fusion protein comprised of the 19-kilodalton merozoite surface protein 1 fused with the murine C4bp domain protects mice against malaria.
Highly purified protein antigens are usually poor immunogens; in practice, adjuvants are needed to obtain satisfactory immune responses. Plasmodium yoelii 19-kDa merozoite surface protein 1 (MSP1(19)) is a weak antigen, but mice vaccinated with this antigen in strong adjuvants can survive an otherwise lethal parasite challenge. Fusion proteins comprising this antigen fused to the oligomerization domain of the murine complement inhibitor C4-binding protein (C4bp) and a series of homologues have been produced. These C4bp domains acted as adjuvants for the fused antigen; the MSP1(19)-murine C4bp fusion protein induced protective immunity in BALB/c mice. Because this fusion protein also induced antibodies against circulating murine C4bp, distantly related C4bp oligomerization domains fused to the same antigen were tested. These homologous domains did not induce antibodies against murine C4bp and, surprisingly, induced higher antibody titers against the antigen than the murine C4bp domain induced. These results demonstrate a new adjuvantlike effect of C4bp oligomerization domains.
Ogun
Solabomi A
SA
Division of Parasitology, National Institute for Medical Research, Mill Hill, London NW7 1AA, United Kingdom.
Dumon-Seignovert
Laurence
L
Marchand
Jean-Baptiste
JB
Holder
Anthony A
AA
Hill
Fergal
F
D000276:Adjuvants, Immunologic; D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D019084:Fluorescent Antibody Technique, Indirect; D006649:Histocompatibility Antigens / Q000276:immunology*; D008288:Malaria / Q000517:prevention & control*; D020066:Merozoite Surface Protein 1 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D018512:Parasitemia / Q000517:prevention & control; D010967:Plasmodium yoelii / Q000276:immunology; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D016415:Sequence Alignment
D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; C489166:C4bp protein, mouse; D006649:Histocompatibility Antigens; D020066:Merozoite Surface Protein 1; D011993:Recombinant Fusion Proteins