Saccharomyces cerevisiae cells that display norovirus P induce both systemic and mucosal neutralizing antibodies

The human norovirus (HuNov) is the leading cause of acute gastroenteritis (AGE) worldwide. Mucosal secretory IgA (sIgA) in the gastrointestinal tract interrupts the interaction between host cells and HuNov, thus inhibiting viral infection. In this study, we constructed a recombinant Saccharomyces cerevisiae (S. cerevisiae) expressing the HuNov P protein (GII. 4) and evaluated its immunogenicity in mice after oral delivery. First, the recombinant S. cerevisiae (EBY100/pYD1-P) efficiently expressed P, as evidenced by western blotting and indirect fluorescent assay. Second, after oral administration, EBY100/pYD1-P, especially the high-dose group (5 × 10⁹ clone formation units), elicited systemic and mucosal immune responses characterized by significant sera IgG, IgA, and mucosal sIgA. More importantly, these antibodies showed a substantial neutralization effect against P. Lastly, EBY100/pYD1-P induced significant P-specific IFN-γ-secreting T cells and IL4-secreting T cells. Collectively, the recombinant S. cerevisiae expressing HuNov P is a promising mucosal vaccine candidate against HuNov.