Monoclonal antibodies (mAbs) are the most rapidly growing class of therapeutics for a wide range
of human diseases. Up-to now CHO cells have been the best compromise between production
capacity and quality because of their capacity to perform close-to-human glycosylation, which is
important proper folding and function of mAbs. Microbial hosts are historically preferred for
recombinant proteins production because of faster and cheaper processes. In the last 15 years, we
have engineered P. pastoris secretory system to perform human-type N-glycosylation. This opens
up the possibility to switch from mammalian cells to yeast for mAbs production. In potential, this
system offers order-of-magnitude enhanced space time yield, which can be exploited either for
more rapid manufacturing response to outbreaks emergencies, or to obtain much larger
production volumes than is presently possible. Our project aims at investigating whether glycoengineered
P. pastoris strains can be engineered with the required fitness, productivity and quality
attributes to disrupt this area of therapeutic production. We will use both rational secretory
system engineering and directed strain evolution strategies. As a first valuable target for this
widely applicable platform, we will focus on the production of a broadly neutralizing anti-influenza
VHH-Fc antibody, based on the conserved N-terminal ectodomain of influenza A M2 protein,
where the speed of the production cycle is critical in case of an outbreak.