All studies complied with the requirements of the Institutional Animal Care and Use Committee (IACUC, 19–806-B). Male CD1 mice (7–8 weeks old) (Crl:CD1(ICR)) were purchased from Charles River Laboratory (Wilmington, MA, USA). RFP-Exo and RFP-Lipo were administered via nebulization (Pari Trek S Portable 459 Compressor Nebulizer Aerosol System; 047F45-LCS, PARI). PBS, Exo, RBD, RBD-Exo treatments (1010 per kg of mouse weight) and RBD-Lipo treatments (1.26 × 1010 per kg of mouse weight) were given in two doses once a week for 2 weeks via nebulization or IV injection. Spike protein (Sino Biological) was modified onto the surface of lentivirus (Cellomics Technology) and the SARS-CoV-2 mimics were synthesized according to our previous report59 (link). Mice were challenged with SARS-CoV-2 mimics labelled with AF647 (106 particles per kg of body weight) by nebulization 1 week after the second treatment dose. Lungs were excised and imaged at days 2 and 6 post vaccination with a Xenogen live imager (PerkinElmer). Blood and all other major organs were collected for further analysis.