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

The COVID-19 pandemic has fostered major advances in vaccination technologies1–4; however, there are urgent needs for vaccines that induce mucosal immune responses and for single-dose, non-invasive administration4–6. Here we develop an inhalable, single-dose, dry powder aerosol SARS-CoV-2 vaccine that induces potent systemic and mucosal immune responses. The vaccine encapsulates assembled nanoparticles comprising proteinaceous cholera toxin B subunits 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 the induction of immune responses. Moreover, this vaccine 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 the vaccine that co-displays ancestral and Omicron antigens, extending the breadth of antibody response against co-circulating strains and transmission of the Omicron variant. These findings support the use of this inhaled vaccine as a promising multivalent platform for fighting COVID-19 and other respiratory infectious diseases. An inhalable, single-dose dry powder aerosol SARS-CoV-2 vaccine shows good storage stability, results in sustained antigen delivery to antigen-presenting cells in the lungs and induces a potent antiviral immune response.