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Infection and Immunity, August 2008, p. 3817-3823, Vol. 76, No. 8
0019-9567/08/$08.00+0     doi:10.1128/IAI.01369-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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{triangledown}

Solabomi A. Ogun,1 Laurence Dumon-Seignovert,2,{dagger} Jean-Baptiste Marchand,2 Anthony A. Holder,1 and Fergal Hill2*

Division of Parasitology, National Institute for Medical Research, Mill Hill, London NW7 1AA, United Kingdom,1 Imaxio SA, 181-203 avenue Jean Jaurès, 69007 Lyon, France2

Received 10 October 2007/ Returned for modification 4 December 2007/ Accepted 3 May 2008

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 (MSP119) 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 MSP119-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.

* Corresponding author. Mailing address: Imaxio SA, 181-203 avenue Jean Jaurès, 69007 Lyon, France. Phone: 33 437 65 55 04. Fax: 33 437 65 06 17. E-mail: fhill{at}imaxio.com

{triangledown} Published ahead of print on 12 May 2008.

Editor: J. F. Urban, Jr.

{dagger} Present address: Metabolic Explorer, Biopôle Clermont-Limagne, 63360 Saint-Beauzire, France.

Infection and Immunity, August 2008, p. 3817-3823, Vol. 76, No. 8
0019-9567/08/$08.00+0     doi:10.1128/IAI.01369-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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