Structural conformers produced during malaria vaccine production in yeast

Abstract

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