A Secreted Subunit SARS-CoV-2 RBD-CpE Yeast Oral Vaccine Induces an Adaptive Immune Response in BALB/c Mice

Despite their differences, all the current COVID-19 vaccines need to be refrigerated and administered intramuscularly by a health care worker. They are also relatively expensive. These characteristics often make COVID-19 vaccine storage, distribution, and administration relatively complex, especially in low- and middle-income countries where refrigeration and healthcare workers are limited. To address these challenges, we are developing a COVID-19 oral vaccine utilizing the yeast Saccharomyces boulardii as a delivery platform. We have successfully engineered recombinant strains of Saccharomyces boulardii to express and secrete the Receptor Binding Domain (RBD) of the Spike protein from the original Wuhan-Hu-1 strain of the SARS- CoV-2 virus, fused to the C-terminal fragment of Clostridium perfringens enterotoxin (CpE). Animal trials suggest that our candidate secreted oral yeast vaccine can elicit detectable RBD- specific IgG and IgA, as well as an IFN-{gamma} but not an IL-4 response, in BALB/c mice. As such, our data suggest that Saccharomyces boulardii remains a promising and novel vaccine delivery platform not only for COVID-19 but also for other infectious diseases.