Malaria continues to be one of the devastating diseases affecting a large population of the world and claims an estimated one to two million lives annually. Unfortunately, there is no vaccine available against malaria. Current recombinant vaccine candidates are only of one or of few antigens that block one stage in the malaria life cycle and are proven not to be effective. We propose combinatorial approach by using yeast and baculovirus to express at least 30 antigens using ubiquitin-fusion technology that targets all three steps in malaria life cycle. Multiple antigens can now be expressed rapidly using new cloning technologies. LifeSensors proposes the attachment of ubiquitin to C-terminus of candidate malaria antigens to dramatically enhance quality and quantity of the proteins. Besides the improvement of protein expression and folding, ubiquitin fusion technique allows to generate proteins with different amino termini and a choice to create uncleaved Ub-antigens. The latter has been shown to increase CTL response upon immunization. The pool of antigens will be tested in mice for immune response, as well as immunofluorescence studies with P. falciprum to localize the antigen interaction. Phase II of this SBIR will include an increase in number of antigens, production of clinical grade material, as well as tests in monkey model. We believe that a highly efficient method of expression of multiple and ubiquitinated antigens will be a novel solution in the development of malaria vaccine.
| Marblestone, Jeffrey G; Edavettal, Suzanne C; Lim, Yiting et al. (2006) Comparison of SUMO fusion technology with traditional gene fusion systems: enhanced expression and solubility with SUMO. Protein Sci 15:182-9 |
| Butt, Tauseef R; Edavettal, Suzanne C; Hall, John P et al. (2005) SUMO fusion technology for difficult-to-express proteins. Protein Expr Purif 43:1-9 |
