Biomedical applications of yeast- a patent view, part one: yeasts as workhorses for the production of therapeutics and vaccines

Abstract

Yeasts, as Eukaryotes, offer unique features for ease of growth and genetic manipulation possibilities, making it an exceptional microbial host. Areas covered: This review provides general and patent-oriented insights into production of biopharmaceuticals by yeasts. Patents, wherever possible, were correlated to the original or review articles. The review describes applications of major GRAS (generally regarded as safe) yeasts for the production of therapeutic proteins and subunit vaccines; additionally, immunomodulatory properties of yeast cell wall components were reviewed for use of whole yeast cells as a new vaccine platform. The second part of the review will discuss yeast- humanization strategies and innovative applications. Expert opinion: Biomedical applications of yeasts were initiated by utilization of Saccharomyces cerevisiae, for production of leavened (fermented) products, and advanced to serve to produce biopharmaceuticals. Higher biomass production and expression/secretion yields, more similarity of glycosylation patterns to mammals and possibility of host-improvement strategies through application of synthetic biology might enhance selection of Pichia pastoris (instead of S. cerevisiae) as a host for production of biopharmaceutical in future. Immunomodulatory properties of yeast cell wall β-glucans and possibility of intracellular expression of heterologous pathogen/tumor antigens in yeast cells have expanded their application as a new platform, 'Whole Yeast Vaccines'.

β-Glucan and parasites

“…The overwhelming conclusion reached from this review is that, as an adjuvant, glucan can be as effective as, and at the same time safer than, conventional bacterial or other adjuvants (Roohvand et al, 2017; Li and Wang, 2015; De Smet et al, 2014). In the last decade, our knowledge of glucan and its mechanisms of action have improved tremendously.…”

Saccharomyces cerevisiae (Baker’s Yeast) as an Interfering RNA Expression and Delivery System

“…Saccharomyces cerevisiae , also known as baker’s or budding yeast, is a non-infectious microbe and genetic model organism. Research in S. cerevisiae has provided key insights into the regulation of many fundamental eukaryotic cellular processes, including the cell cycle, signal transduction, chromatin structure, transcription, and genetic inheritance [1, 2]. Despite the many attributes of this model system, RNA interference (RNAi), a regulatory pathway in eukaryotic cells that silences gene expression through the production of small interfering RNAs (siRNAs), has not traditionally been studied in S. cerevisiae [1], which lacks components of the RNAi pathway [3].…”

Oral Administration of Recombinant Saccharomyces boulardii Expressing Ovalbumin-CPE Fusion Protein Induces Antibody Response in Mice

“…Taken together, the results of the present study indicate the use of S. boulardii as a probiotic with the ability of delivering immunogenic or therapeutic proteins to intestinal lumen via oral administration. Similar studies using different engineered yeasts have also shown promising results, leading to the description of “Whole Yeast Vaccine” as a new platform for vaccine development ( Shin et al, 2007 ; Wang et al, 2016 ; Roohvand et al, 2017 ). Although we did not investigate the presence of intact antigens in the intestinal lumen, the induction of both serum IgG and fecal IgA responses indicate the release and accessibility of the recombinant antigen to the immune effector cells.…”