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

Nature. 2023 Dec;624(7992):630-638. doi: 10.1038/s41586-023-06809-8. Epub 2023 Dec 13.


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.

MeSH terms

  • Administration, Inhalation
  • Aerosols
  • Animals
  • Antibodies, Viral / immunology
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism
  • Antigens, Viral / immunology
  • COVID-19 / immunology
  • COVID-19 / prevention & control
  • COVID-19 Vaccines* / administration & dosage
  • Capsules
  • Cholera Toxin
  • Cricetinae
  • Humans
  • Immunity, Mucosal* / immunology
  • Immunoglobulin A / immunology
  • Immunoglobulin G / immunology
  • Mice
  • Nanoparticles
  • Powders
  • Primates / virology
  • SARS-CoV-2 / classification
  • SARS-CoV-2 / immunology
  • T-Lymphocytes / immunology
  • Vaccination


  • Aerosols
  • Antibodies, Viral
  • Antigens, Viral
  • Cholera Toxin
  • COVID-19 Vaccines
  • Immunoglobulin A
  • Immunoglobulin G
  • Powders
  • Capsules
  • spike protein, SARS-CoV-2

Supplementary concepts

  • SARS-CoV-2 variants