Production of Functional Anti-Ebola Antibodies in Pichia pastoris.

TitleProduction of Functional Anti-Ebola Antibodies in Pichia pastoris.
Publication TypeJournal Article
Year of Publication2017
AuthorsPurcell, O, Opdensteinen, P, Chen, W, Lowenhaupt, K, Brown, A, Hermann, M, Cao, J, Tenhaef, N, Kallweit, E, Kastilan, R, Sinskey, AJ, Perez-Pinera, P, Buyel, JF, Lu, TK
JournalACS Synth Biol
Volume6
Issue12
Pagination2183-2190
Date Published2017 Dec 15
ISSN2161-5063
KeywordsAntibodies, Monoclonal, Antibodies, Viral, Ebolavirus, Gene Expression, Humans, Pichia, Recombinant Proteins
Abstract

The 2013-2016 Ebola outbreak highlighted the limited treatment options and lack of rapid response strategies for emerging pathogen outbreaks. Here, we propose an efficient development cycle using glycoengineered Pichia pastoris to produce monoclonal antibody cocktails against pathogens. To enable rapid genetic engineering of P. pastoris, we introduced a genomic landing pad for reliable recombinase-mediated DNA integration. We then created strains expressing each of the three monoclonal antibodies that comprise the ZMapp cocktail, and demonstrated that the secreted antibodies bind to the Ebola virus glycoprotein by immunofluorescence assay. We anticipate that this approach could accelerate the production of therapeutics against future pathogen outbreaks.

DOI10.1021/acssynbio.7b00234
Alternate JournalACS Synth Biol
Citation Key59
PubMed ID28786662