, a bio/informatics shared resource is still "open for business" - Visit the CDS website


Construction and immunogenicity in mice of attenuated Salmonella typhi expressing Plasmodium falciparum merozoite surface protein 1 (MSP-1) fused to tetanus toxin fragment C.

Wu S, Beier M, Sztein MB, Galen J, Pickett T, Holder AA, Gómez-Duarte OG, Levine MM
J Biotechnol. 2000 83 (1-2): 125-35

PMID: 11000468 · DOI:10.1016/s0168-1656(00)00306-0

One strategy to develop a multi-antigen malaria vaccine is to employ live vectors to carry putative protective Plasmodium falciparum antigens to the immune system. The 19 kDa carboxyl terminus of P. falciparum merozoite surface protein 1 (MSP-1), which is essential for erythrocyte invasion and is a leading antigen for inclusion in a multivalent malaria vaccine, was genetically fused to fragment C of tetanus toxin and expressed within attenuated Salmonella typhi CVD 908. Under conditions in the bacterial cytoplasm, the fragment C-MSP-1 fusion did not form the epidermal growth factor (EGF)-like domains of MSP-1; monoclonal antibodies failed to recognize these conformational domains in immunoblots of non-denatured protein extracted from live vector sonicates. The MSP-1 was nevertheless immunogenic. One month following intranasal immunization of BALB/c mice with the live vector construct, four out of five mice exhibited > or =four-fold rises in anti-MSP-1 by ELISA (GMT=211); a single intranasal booster raised titers further (GMT=1280). Post-immunization sera recognized native MSP-1 on merozoites as determined by indirect immunofluorescence. These data encourage efforts to optimize MSP-1 expression in S. typhi (e.g. as a secreted protein), so that the EGF-like epitopes, presumably necessary for stimulating protective antibodies, can form.

MeSH Terms (13)

Animals Base Sequence Cloning, Molecular DNA Primers Enzyme-Linked Immunosorbent Assay Immunity, Mucosal Merozoite Surface Protein 1 Mice Mice, Inbred BALB C Peptide Fragments Plasmodium falciparum Salmonella typhi Tetanus Toxin

Connections (1)

This publication is referenced by other Labnodes entities:

Links