Polyethyleneimine-complexed charge-reversed yeast cell walls for the enhanced oral delivery of pseudovirus-based antigens.

Oral vaccination has wide applicability in poor areas, particularly during the epidemic periods of infectious diseases. However, successful oral antigen delivery and immune activation remain highly challenging due to the instability of vaccines in gastric acid and the low capture of antigens in the intestine. Here, we present a facile approach for the preparation of a robust oral delivery system via encapsulating antigen-carrying pseudoviruses inside positively charged polyethyleneimine-modified yeast capsules (P-YC). By virtue of the physical barrier role and surface β-glucan of YC, encapsulated pseudoviruses can be protected from gastric insult and delivered into Peyer's patches via uptake mediated by microfold cells located in the intestinal epithelium. Given the ability to carry diverse antigens, the enhanced oral delivery of pseudoviruses achieved by P-YC provides a versatile platform for the development of various oral vaccines.