Wang, ZhenzhenPopowski, Kristen DZhu, Dashuaide Juan Abad, Blanca LópezWang, XianyunLiu, MengruiLutz, HalleDe Naeyer, NicoleDeMarco, C ToddDenny, Thomas NDinh, Phuong-Uyen CLi, ZhenhuaCheng, Ke2022-08-082022-08-082022-07-042157-846X2157-846Xhttps://hdl.handle.net/10161/25587The first two mRNA vaccines against infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that were approved by regulators require a cold chain and were designed to elicit systemic immunity via intramuscular injection. Here we report the design and preclinical testing of an inhalable virus-like-particle as a COVID-19 vaccine that, after lyophilisation, is stable at room temperature for over three months. The vaccine consists of a recombinant SARS-CoV-2 receptor-binding domain (RBD) conjugated to lung-derived exosomes which, with respect to liposomes, enhance the retention of the RBD in both the mucus-lined respiratory airway and in lung parenchyma. In mice, the vaccine elicited RBD-specific IgG antibodies, mucosal IgA responses and CD4⁺ and CD8⁺ T cells with a Th1-like cytokine expression profile in the animals' lungs, and cleared them of SARS-CoV-2 pseudovirus after a challenge. In hamsters, two doses of the vaccine attenuated severe pneumonia and reduced inflammatory infiltrates after a challenge with live SARS-CoV-2. Inhalable and room-temperature-stable virus-like particles may become promising vaccine candidates.CD8-Positive T-LymphocytesAnimalsMice, Inbred BALB CHumansMiceViral VaccinesExosomesAntibodies, NeutralizingCOVID-19SARS-CoV-2COVID-19 VaccinesJournal article2022-08-08