VACCINE. Development of a novel yeast-based oral subunit vaccine against Eimeria spp. in chickens

点击翻译按钮获取中文摘要

Yeast species such as Saccharomyces cerevisiae are useful tools for the high yield production of recombinant proteins and have a Generally Regarded As Safe (GRAS) status. They are capable of performing several complex post-translational modifications that are not achieved in many other expression systems, and are easily grown to very high densities producing large quantities of stable particles. Recently, the idea of using S. cerevisiae as a delivery vehicle for cancer, viral, and bacterial vaccines has been explored, inducing robust humoral and cellular immune responses. In addition to using yeast to produce a vaccine antigen of interest, the yeast cell itself has been shown to have adjuvant-like properties and has the potential to activate both inflammatory and phagocytic receptors expressed on antigen-presenting cells. Our preliminary data demonstrates that freeze-drying recombinant yeast cultures expressing viral protein at their surface renders the recombinant yeast completely non-viable (unpublished). However, the freeze-drying process does not alter conformation of these proteins, as surface expression is equal in live and freeze-dried yeast as quantified by flow cytometry and Western blotting. This has interesting implications in vaccine design as a non-viable S. cerevisiae is not categorised as a genetically modified organism (GMO) and such a killed vaccine would not be subject to GMO regulations. Additionally there would be no need for refrigeration of the freeze-dried yeast, reducing transport and storage costs. Vaccines based upon S. cerevisiae are likely to be particularly valuable against diseases of farmed poultry, where safety, scalability, stability, delivery and cost are crucial. In one example modern poultry production relies on effective control of Eimeria, but current approaches using drugs and live vaccines require improvement. In recent years a panel of coccidial antigens have been identified as vaccine candidates, each individually capable of inducing up to a 65% reduction in oocyst output. Now, the focus is shifting from antigen discovery to antigen formulation and delivery with yeast being a leading option, especially given the importance of T-cell mediated responses in anticoccidial immunity.