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

Makoto Kuroda, Peter J. Halfmann (), Ryuta Uraki, Seiya Yamayoshi, Taksoo Kim, Tammy A. Armbrust, Sam Spyra, Randall Dahn, Lavanya Babujee and Yoshihiro Kawaoka ()
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Makoto Kuroda: University of Wisconsin
Peter J. Halfmann: University of Wisconsin
Ryuta Uraki: University of Tokyo
Seiya Yamayoshi: University of Tokyo
Taksoo Kim: University of Wisconsin
Tammy A. Armbrust: University of Wisconsin
Sam Spyra: University of Wisconsin
Randall Dahn: University of Wisconsin
Lavanya Babujee: University of Wisconsin
Yoshihiro Kawaoka: University of Wisconsin

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-59533-4

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