Production of Functional Anti-Ebola Antibodies in Pichia pastoris

ACS Synth Biol. 2017 Dec 15;6(12):2183-2190. doi: 10.1021/acssynbio.7b00234. Epub 2017 Aug 17.

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.

Keywords: Ebola; Pichia pastoris; antibodies; biologics.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antibodies, Monoclonal* / biosynthesis
  • Antibodies, Monoclonal* / genetics
  • Antibodies, Monoclonal* / immunology
  • Antibodies, Viral* / biosynthesis
  • Antibodies, Viral* / genetics
  • Antibodies, Viral* / immunology
  • Ebolavirus / immunology*
  • Gene Expression*
  • Humans
  • Pichia* / genetics
  • Pichia* / immunology
  • Pichia* / metabolism
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology

Substances

  • Antibodies, Monoclonal
  • Antibodies, Viral
  • Recombinant Proteins