Norovirus capsid protein expressed in yeast forms virus-like particles and stimulates systemic and mucosal immunity in mice following an oral administration of raw yeast extracts.

Norovirus (NV) gastroenteritis is a widespread disease affecting people of all ages worldwide. A simple, safe, and easily deliverable vaccine may be the key for the control and prevention of NV gastroenteritis. In this study, we demonstrated that a NV recombinant capsid protein (strain VA387, genogroup II.4) expressed in yeast (Pichia pastoris) spontaneously formed virus-like particles (VLPs) like those expressed in other in vitro systems. Oral administration of raw material from the yeast cell lysates containing 0.1 mg of VLPs without an adjuvant resulted in systemic and mucosal immune responses in mice. Significantly higher and earlier responses were observed in mice receiving a higher dose (1 mg per dose) of the antigen. Both the serum and fecal antibodies blocked VA387 VLP binding to its histo-blood group antigen receptors. The animals did not reveal any side effect following the administration of the yeast lysates. Our results indicated that yeast is a simple, effective alternative for NV VLP production. The mice immunization study also indicated that the oral administration of raw yeast extracts without an adjuvant is a safe and simple way which is worth to be studied for vaccine delivery in humans.