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Expression of disulphide-bridge-dependent conformational epitopes and immunogenicity of the carboxy-terminal 19 kDa domain of Plasmodium yoelii merozoite surface protein-1 in live attenuated Salmonella vaccine strains

Elizabeth A. Somner

Department of Microbiology, The Medical School, University of Newcastle, Newcastle upon Tyne NE2 4HH, UK
Division of Parasitology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK

Author for correspondence: C. M. Anjam Khan. Tel: +44 191 222 7066. Fax: +44 191 222 7736. e-mail: anjam.khan@newcastle.ac.uk

ABSTRACT

Summary: The 19 kDa carboxy-terminal domain of Plasmodium yoelii merozoite surface protein-1 (MSP1¹⁹) was expressed in Salmonella vaccine strains as a carboxy-terminal fusion to fragment C of tetanus toxin (TetC). This study demonstrates that antibodies that recognize disulphide-dependent conformational epitopes in native MSP1 react with the TetC-MSP1₁₉ fusion protein expressed in Salmonella. The proper folding of MSP1₁₉ polypeptide is dependent on both the Salmonella host strain and the protein to which the MSP1₁₉ polypeptide is fused. Serum from mice immunized with Salmonella typhimurium C5aroD expressing TetC-MSP1₁₉ recognized native MSP1 as shown by immunofluorescence with P. yoelii-infected erythrocytes. Antibody levels to MSP1₁₉ were highest in out-bred mice immunized with S. typhimurium C5aroD carrying pTECH2-MSP1₁₉ and antibody was mostly directed against reduction-sensitive conformational epitopes. However, antibody levels were lower than in BALB/c mice immunized with a glutathione S-transferase (GST)-MSP1₁₉ fusion protein in Freund's adjuvant, and which were protected against P. yoelii challenge infection. In challenge experiments with P. yoelii the Salmonella-immunized mice were not protected, probably reflecting the magnitude of the antibody response. The results of this study have important implications in the design of live multivalent bacterial vaccines against eukaryotic pathogens.

Present address: Department of Infection and Tropical Medicine, The Lister Unit, Northwick Park Hospital, Harrow HA1 3UJ, UK.

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