Establishment of a Novel Platform for Developing Oral Vaccines Based on the Surface Display System of Yeast Spores

Oral vaccines are currently the focus of vaccine development because they are convenient to administer, easy to distribute, and capable of activating mucosal immunity. However, the complexity of the gastrointestinal environment and the lack of delivery vehicles severely limit the stability and effectiveness of oral vaccines. This study established a novel platform for developing oral vaccines based on the surface display system of yeast spores. As a specific example, oral vaccines for COVID-19, designed by displaying the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein on the surface of three <i>Saccharomyces cerevisiae</i> spore types, including AN120, <i>osw2</i>Δ, and <i>dit1</i>Δ, were constructed and evaluated. The displayed RBD showed perfect gastrointestinal stability in vitro and was validated in animal studies to produce effective humoral immunity and significant mucosal immune responses after the vaccination. Notably, the displayed RBD elicited a cellular immune response skewed towards a T-helper type 1 (Th1) cell direction in a mouse model. Our findings proved that the oral vaccines of <i>S. cerevisiae</i> spores could rapidly induce a comprehensive and protective immune response to SARS-CoV-2. This study aims to provide a promising and potentially useful system that can be used to develop other oral vaccines.