Exosomes decorated with a recombinant SARS-CoV-2 receptor-binding domain as an inhalable COVID-19 vaccine

An inhalable virus-like-particle consisting of exosomes decorated with a recombinant SARS-CoV-2 receptor-binding domain is stable at room temperature and elicits systemic and mucosal immune responses in small animals. The 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.

Automated summary

Researchers have developed an inhalable and room-temperature-stable virus-like particle COVID-19 vaccine that induces systemic and mucosal immune responses in small animals. The vaccine, consisting of a recombinant SARS-CoV-2 receptor-binding domain conjugated to lung-derived exosomes, enhanced the retention of the receptor-binding domain in the respiratory airway and lungs, and cleared SARS-CoV-2 pseudovirus in mice. In hamsters, the vaccine attenuated severe pneumonia and reduced inflammatory infiltrates after a challenge with live SARS-CoV-2.