Inhalable SARS-CoV-2 vaccine for single-dose dry powder aerosol immunization

Abstract The coronavirus disease pandemic has fostered major advances in vaccination technologies; however, there are urgent needs for vaccines that induce mucosal immune responses and single-dose, noninvasive administration. Here, we develop an inhalable, single-dose, dry powder aerosol SARS-CoV-2 vaccine that induces potent systemic and mucosal immune responses. Our vaccine encapsulates proteinaceous cholera toxin B subunit-assembled nanoparticles displaying the SARS-CoV-2 RBD antigen within microcapsules of optimal aerodynamic size, and this unique nano-micro coupled structure supports efficient alveoli delivery, sustained antigen release, and antigen-presenting cell uptake, which are favourable features for induction of immune responses. Moreover, our vaccine successfully induces strong production of IgG and IgA, as well as a local T-cell response, collectively conferring effective protection against SARS-CoV-2 in mice, hamsters, and nonhuman primates. Finally, we also demonstrate a “mosaic iteration” of our vaccine that codisplays ancestral and Omicron antigens, extending the breadth of antibody response against cocirculating strains and transmission of the Omicron variant. These findings support our inhalable vaccine as a promising multivalent platform for fighting COVID-19 or other respiratory infectious diseases.