The circumsporozoite protein (CSP), present in the sporozoite stage of the malaria parasite’s lifecycle, has long been a target of recombinant antigen development, as both a reagent and in the development of vaccine candidates.
The expression, purification, and stabilization of the full-length CSP molecule has proved cumbersome in common heterologous expression systems, due to the extensive repeat region of CSP and need of proper disulfide bond pairing (to afford proper structure/conformation of the protein).
Statens Serum Institut (SSI) has successfully used Lactococcus lactis, a gram-positive bacterium, for the expression of multiple malaria antigen targets including regions of the Pfs48/45 molecule, and has successfully applied the expression system for the production of full-length CSP. SSI, with the support of PATH, is now undertaking process development of CSP to establish a scalable process for the supply of CSP protein, in addition to conducting stability studies and analytical development of assays to assist in the characterization of the protein. SSI will also develop and evaluate additional CSP constructs, including reduced repeats, to supply PATH and its partners suitable reagent protein to support a multitude of projects.