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Publications

Journal Article Epublish

PubMed: 40360482 DOI: 10.1038/s41467-025-59533-4

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

Nat Commun 16(1):4453

Authors: Makoto Kuroda, Peter J Halfmann, Ryuta Uraki, Seiya Yamayoshi, Taksoo Kim, Tammy A Armbrust, Sam Spyra, Randall Dahn, Lavanya Babujee, Yoshihiro Kawaoka

Affiliations

  • Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, 53711, USA.
  • Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, 53711, USA.
  • Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, 108-8639, Japan.
  • The Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute, Tokyo, 162-8655, Japan.
  • Pandemic Preparedness, Infection and Advanced Research Center (UTOPIA), University of Tokyo, Tokyo, 162-8655, Japan.
  • International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, 162-8655, Japan.
  • Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, 53711, USA.
  • Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, 108-8639, Japan.
  • The Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute, Tokyo, 162-8655, Japan.
  • Pandemic Preparedness, Infection and Advanced Research Center (UTOPIA), University of Tokyo, Tokyo, 162-8655, Japan.

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.

MeSH

Cells, Sars-Cov-2, Reading, Vaccines, Biological Science Disciplines, Covid-19 Vaccines, Open Reading Frames, Vaccination, Viruses, Severe Acute Respiratory Syndrome-Related Coronavirus, Tissues, Reading Frames, Membranes