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Production, quality control, stability and pharmacotoxicity of a malaria vaccine comprising three highly similar PfAMA1 protein molecules to overcome antigenic variation

: Faber, B.W.; Hellwig, S.; Houard, S.; Havelange, N.; Drossard, J.; Mertens, H.; Croon, A.; Kastilan, R.; Byrne, R.; Werff, N. van der; Eijk, M. van der; Thomas, A.W.; Kocken, C.H.M.; Remarque, E.J.

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PLoS one. Online journal 11 (2016), Nr.10, Art. e0164053, 32 S.
ISSN: 1932-6203
Zeitschriftenaufsatz, Elektronische Publikation
Fraunhofer IME ()

Plasmodium falciparum apical membrane antigen 1 (PfAMA1) is a leading asexual blood stage vaccine candidate for malaria. In preparation for clinical trials, three Diversity Covering (DiCo) PfAMA1 ectodomain proteins, designed to overcome the intrinsic polymorphism that is present in PfAMA1, were produced under Good Manufacturing Practice (GMP) in Pichia pastoris. Using identical methodology, the 3 strains were cultivated in 70-L scale fed-batch fermentations and PfAMA1-DiCos were purified by two chromatography steps, an ultrafiltration/diafiltration procedure and size exclusion chromatography, resulting in highly pure (>95%) PfAMA1-DiCo1, PfAMA1 DiCo2 and PfAMA1 DiCo3, with final yields of 1.8, 1.9 and 1.3 gram, respectively. N-terminal determinations showed that approximately 50% of each of the proteins lost 12 residues from their N-terminus, in accordance with SDS-PAGE (2 main bands) and MS-data. Under reducing conditions a site of limited proteolytic cleavage within a disulphide bonded region bec