Several genes encoding the Plasmodium falciparum Circumsporozoite (CS) protein has been designed, synthesized, and cloned into an E. coli and P. pastoris expression vectors. One recombinant CS protein (rCSP) with sequence corresponding to P. falciparum strain India was produced. The protein will be conjugated to carrier proteins, e.g. a recombinant exoprotein A from Pseudomonas aruginosa, and conjugated Pfs25. Efforts continue to produce the CSP in the Pichia pastoris expression system. A mouse model using a transgenic berghei parasite expressing falciparum CSP on its sporozoite surface is being developed and tested as an assay to evaluate protection imparted by a CSP-based vaccine. We are also creating a transgenic knowelsi parasite, expressing falciparum CSP on its sporozoite surface, to establish a monkey challenge model for evaluating protective efficacy of CSP-based vaccines.

Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2009
Total Cost
$1,793,249
Indirect Cost
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State
Country
Zip Code
Kubler-Kielb, Joanna; Majadly, Fathy; Biesova, Zuzana et al. (2010) A bicomponent Plasmodium falciparum investigational vaccine composed of protein-peptide conjugates. Proc Natl Acad Sci U S A 107:1172-7
Plassmeyer, Matthew L; Reiter, Karine; Shimp Jr, Richard L et al. (2009) Structure of the Plasmodium falciparum circumsporozoite protein, a leading malaria vaccine candidate. J Biol Chem 284:26951-63