Scaffolded Antigens in Yeast Cell Particle Vaccines Provide Protection against Systemic Polyoma Virus Infection

Background. u65,a self-aggregating peptide scaffold,traps fused protein antigens in yeast cells. conversion to yeast cell particle (ycp) vaccines by partial removal of surface mannoproteins exposes β-glucan,mediating efficient uptake by antigen-presenting cells (apcs). ycp vaccines are inexpensive,capable of rapid large-scale production and have potential for both parenteral and oral use. results. ycp processing by alkaline hydrolysis exposes up to 20% of the glucan but converts scaffolded antigen and internal yeast proteins into a common aggregate,preventing selective yeast protein removal. for u65-green fluorescent protein (gfp) or u65-apolipoprotein a1 (apoa1) subcutaneous vaccines,maximal igg responses in mice required 10% glucan exposure. igg responses to yeast proteins were 5-fold lower. proteolytic mannoprotein removal produced ycps with only 6% glucan exposure,insufficiently porous for selective removal of even native yeast proteins. vaccine efficacy was reduced 10-fold. current ycp formulations,therefore,are not suitable for human use but have considerable potential for use in feed animal vaccines. significantly,a ycp vaccine expressing a gfp fusion to vp1,the murine polyoma virus major capsid protein,after either oral or subcutaneous administration,protected mice against an intraperitoneal polyoma virus challenge,reducing viral dna levels in spleen and liver by >98%. � 2016 donald j. tipper and eva szomolanyi-tsuda.