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Structural conformers produced during malaria vaccine production in yeast
Author(s) -
Stowers Anthony W.,
Zhang Yanling,
Shimp Richard L.,
Kaslow David C.
Publication year - 2001
Publication title -
yeast
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.923
H-Index - 102
eISSN - 1097-0061
pISSN - 0749-503X
DOI - 10.1002/1097-0061(20010130)18:2<137::aid-yea657>3.0.co;2-x
Subject(s) - biology , epitope , antigen , saccharomyces cerevisiae , malaria vaccine , recombinant dna , plasmodium falciparum , virology , computational biology , microbiology and biotechnology , biochemistry , yeast , immunology , gene , malaria
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.