Structural conformers produced during malaria vaccine production in yeast

A recombinant protein expression system based on Saccharomyces cerevisiae h as been used to express malarial vaccine candidate antigens, The antigens s o produced have been used in three Phase 1 clinical trials and numerous pre clinical non-human primate trials, Further Phase I trials are planned using these candidate vaccine antigens, These molecules were identified as attra ctive candidates for antimalarial vaccines, as they are all surface-exposed at some stage in the parasite's life cycle. They all share an unusual stru ctural feature: epidermal growth factor (EGF)-like motifs, When these prote ins are expressed in our S, cerevisiae expression system, they are produced as a series of stable structural conformers, each with a different disulph ide bonding pattern. This leads to both biochemical and, more importantly, antigenic differences between the conformers (e.g. presence or absence of a n antibody B cell epitope), These findings have important ramifications for other EGF-domain-containing proteins expressed in S, cerevisiae, or for pr oteins which contain other cysteine-folding motifs not normally expressed b y this organism, both for vaccine production or for research/reagent purpos es. Copyright (C) 2000 John Wiley & Sons, Ltd.