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

Donald J Tipper,Eva Szomolanyi-Tsuda

doi:10.1155/2016/2743292

Donald J Tipper, Eva Szomolanyi-Tsuda

Open Access

https://doi.org/10.1155/2016/2743292

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Abstract

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%.

Highlights

IntroductionGlucan particles (GPs), prepared from the walls of Saccharomyces cerevisiae cells, are composed primarily of β-1,3-Dglucans (βG) [1, 2]
Glucan particles (GPs), prepared from the walls of Saccharomyces cerevisiae cells, are composed primarily of β-1,3-Dglucans [1, 2]. These are recognized as a fungal cell wall pathogen-associated molecular pattern (PAMP) and GPs serve as an effective adjuvant for IgG antibody production when admixed with free antigens [3]
We demonstrate that Yeast Cell Particle (YCP) made from both U65- and U76LGFP and Apolipoprotein A1 (ApoA1) fusions were highly effective in eliciting IgG responses in mice and determine the minimal % glucan exposure sufficient for optimal immune responses

Summary

Introduction

Glucan particles (GPs), prepared from the walls of Saccharomyces cerevisiae cells, are composed primarily of β-1,3-Dglucans (βG) [1, 2]. The particles have far broader efficacy when the antigen is encapsulated inside GPs, ensuring codelivery of both glucan adjuvant and antigen to the same endosomal compartment in the same antigenpresenting cell (APC) [3]. Robust antibody and both Th1- and Th17-biased CD4 T cell responses result [3]. Recombinant yeast cells expressing protein antigens should have similar advantages for codelivery of antigen and adjuvant, and several reports describe their use as oral vaccines in feed animals [8]. 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%

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