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

Author

Listed:
  • Makoto Kuroda

    (University of Wisconsin)

  • Peter J. Halfmann

    (University of Wisconsin)

  • Ryuta Uraki

    (University of Tokyo
    National Center for Global Health and Medicine Research Institute
    University of Tokyo)

  • Seiya Yamayoshi

    (University of Tokyo
    National Center for Global Health and Medicine Research Institute
    University of Tokyo
    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
    University of Tokyo
    National Center for Global Health and Medicine Research Institute
    University of Tokyo)

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.

Suggested Citation

  • Makoto Kuroda & Peter J. Halfmann & Ryuta Uraki & Seiya Yamayoshi & Taksoo Kim & Tammy A. Armbrust & Sam Spyra & Randall Dahn & Lavanya Babujee & Yoshihiro Kawaoka, 2025. "SARS-CoV-2 virus lacking the envelope and membrane open-reading frames as a vaccine platform," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59533-4
    DOI: 10.1038/s41467-025-59533-4
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