Inhalable SARS-CoV-2 Mimetic Particles Induce Pleiotropic Antigen Presentation

Covid-19 has caused over 4.5 million deaths worldwide and continues to ravage communities with limited access to injectable vaccines, or high rates of vaccine hesitancy. Inhalable vaccines have the potential to address these distribution and compliance issues as they are less likely to require cold storage, avoid the use of needles, and can elicit potent localized immune responses with only a single dose. Alveolar macrophages represent attractive targets for inhalable vaccines as they are abundant within lung mucosa (90-95% of all immune cells), are important mediators of mucosal immunity, and evidence suggests may be key cellular players in early Covid-19 pathogenesis. Here, we report inhalable coronavirus mimetic particles (CoMiP) designed to rapidly bind to, and be internalized by, alveolar macrophages to deliver nucleic acid encoded viral antigens. Inspired by the SARS-CoV-2 virion structure, CoMiPs package nucleic acid cargo within an endosomolytic peptide envelope that is wrapped in a macrophage-targeting glycosaminoglycan coating. Through this design, CoMiP carriers mimic several important features of the SARS-CoV-2 virion, particularly surface topography and macromolecular chemistry. As a result, CoMiPs effect pleiotropic transfection of macrophage and lung epithelial cells in vitro with multiple antigen-encoding plasmids. In vivo immunization yields increased mucosal IgA levels within the respiratory tract of CoMIP vaccinated mice.Funding: Funding for this work was provided by the COVID Research Seed Fund from the Huck Institutes of the Life Sciences and Materials Research Institute at the Pennsylvania State University.Declaration of Interests: None to declare. Ethics Approval Statement: Animal care committee is PSU IACUC, under protocol number 001552.