tetano
Editor, Senior Moderator
Nat Biomed Eng
. 2022 Jul 4.
doi: 10.1038/s41551-022-00902-5. Online ahead of print.
Exosomes decorated with a recombinant SARS-CoV-2 receptor-binding domain as an inhalable COVID-19 vaccine
Zhenzhen Wang[SUP] #[/SUP][SUP] 1 2 [/SUP], Kristen D Popowski[SUP] #[/SUP][SUP] 1 [/SUP], Dashuai Zhu[SUP] 1 2 [/SUP], Blanca López de Juan Abad[SUP] 1 [/SUP], Xianyun Wang[SUP] 1 2 [/SUP], Mengrui Liu[SUP] 1 2 [/SUP], Halle Lutz[SUP] 1 [/SUP], Nicole De Naeyer[SUP] 3 [/SUP], C Todd DeMarco[SUP] 3 [/SUP], Thomas N Denny[SUP] 3 [/SUP], Phuong-Uyen C Dinh[SUP] 1 [/SUP], Zhenhua Li[SUP] #[/SUP][SUP] 4 5 6 [/SUP], Ke Cheng[SUP] 7 8 9 [/SUP]
Affiliations
Abstract
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[SUP]+[/SUP] and CD8[SUP]+[/SUP] 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.
. 2022 Jul 4.
doi: 10.1038/s41551-022-00902-5. Online ahead of print.
Exosomes decorated with a recombinant SARS-CoV-2 receptor-binding domain as an inhalable COVID-19 vaccine
Zhenzhen Wang[SUP] #[/SUP][SUP] 1 2 [/SUP], Kristen D Popowski[SUP] #[/SUP][SUP] 1 [/SUP], Dashuai Zhu[SUP] 1 2 [/SUP], Blanca López de Juan Abad[SUP] 1 [/SUP], Xianyun Wang[SUP] 1 2 [/SUP], Mengrui Liu[SUP] 1 2 [/SUP], Halle Lutz[SUP] 1 [/SUP], Nicole De Naeyer[SUP] 3 [/SUP], C Todd DeMarco[SUP] 3 [/SUP], Thomas N Denny[SUP] 3 [/SUP], Phuong-Uyen C Dinh[SUP] 1 [/SUP], Zhenhua Li[SUP] #[/SUP][SUP] 4 5 6 [/SUP], Ke Cheng[SUP] 7 8 9 [/SUP]
Affiliations
- PMID: 35788687
- DOI: 10.1038/s41551-022-00902-5
Abstract
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[SUP]+[/SUP] and CD8[SUP]+[/SUP] 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.