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Nat Commun . SARS-CoV-2 virus lacking the envelope and membrane open-reading frames as a vaccine platform

tetano

Editor, Senior Moderator
Nat Commun


. 2025 May 14;16(1):4453.
doi: 10.1038/s41467-025-59533-4. SARS-CoV-2 virus lacking the envelope and membrane open-reading frames as a vaccine platform

Makoto Kuroda[SUP] #[/SUP][SUP] 1 [/SUP], Peter J Halfmann[SUP] #[/SUP][SUP] 2 [/SUP], Ryuta Uraki[SUP] #[/SUP][SUP] 3 4 5 [/SUP], Seiya Yamayoshi[SUP] 3 4 5 6 [/SUP], Taksoo Kim[SUP] 1 [/SUP], Tammy A Armbrust[SUP] 1 [/SUP], Sam Spyra[SUP] 1 [/SUP], Randall Dahn[SUP] 1 [/SUP], Lavanya Babujee[SUP] 1 [/SUP], Yoshihiro Kawaoka[SUP] 7 8 9 10 [/SUP]



Affiliations
Abstract

To address the need for broadly protective SARS-CoV-2 vaccines, we developed an attenuated a SARS-CoV-2 vaccine virus that lacks the open reading frames of two viral structural proteins: the envelope (E) and membrane (M) proteins. This vaccine virus (ΔEM) replicates in a cell line stably expressing E and M but not in wild-type cells. Vaccination with ΔEM elicits a CD8 T-cell response against the viral spike and nucleocapsid proteins. Two vaccinations with ΔEM provide better protection of the lower respiratory tissues than a single dose against the Delta and Omicron XBB variants in hamsters. Moreover, ΔEM is effective as a booster in hamsters previously vaccinated with an mRNA-based vaccine, providing higher levels of protection in both respiratory tissues compared to the mRNA vaccine booster. Collectively, our data demonstrate the feasibility of a SARS-CoV-2 ΔEM vaccine candidate virus as a vaccine platform.


 
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