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

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...

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Published inNature communications Vol. 16; no. 1; pp. 4453 - 14
Main Authors Kuroda, Makoto, Halfmann, Peter J., Uraki, Ryuta, Yamayoshi, Seiya, Kim, Taksoo, Armbrust, Tammy A., Spyra, Sam, Dahn, Randall, Babujee, Lavanya, Kawaoka, Yoshihiro
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 14.05.2025
Nature Publishing Group
Nature Portfolio
Subjects
631/1647/334/1874/1535
631/326/590/1867
631/326/596/4130
Animals
Antibodies, Viral - immunology
CD8 antigen
CD8-Positive T-Lymphocytes - immunology
Coronavirus Envelope Proteins
COVID-19
COVID-19 - immunology
COVID-19 - prevention & control
COVID-19 - virology
COVID-19 Vaccines - administration & dosage
COVID-19 Vaccines - genetics
COVID-19 Vaccines - immunology
Cricetinae
Female
Hamsters
Humanities and Social Sciences
Humans
Immunization
Immunization, Secondary
Immunoglobulin A
Lymphocytes
Lymphocytes T
Membranes
Mesocricetus
mRNA
multidisciplinary
Nucleocapsids
Open reading frames
Open Reading Frames - genetics
Proteins
SARS-CoV-2 - genetics
SARS-CoV-2 - immunology
Science
Science (multidisciplinary)
Severe acute respiratory syndrome coronavirus 2
Spike Glycoprotein, Coronavirus - genetics
Spike Glycoprotein, Coronavirus - immunology
Structural proteins
Vaccination
Vaccines
Vaccines, Attenuated - administration & dosage
Vaccines, Attenuated - genetics
Vaccines, Attenuated - immunology
Viral diseases
Viruses
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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. In this study, the authors report a single cycle-replicating SARS-CoV-2 vaccine candidate virus (ΔEM) and show that it induces spike-specific IgA and CD8+ T cells targeting spike and nucleocapsid proteins and provides broad and efficient protection in vaccinated animals.
AbstractList 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.
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.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.
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. In this study, the authors report a single cycle-replicating SARS-CoV-2 vaccine candidate virus (ΔEM) and show that it induces spike-specific IgA and CD8+ T cells targeting spike and nucleocapsid proteins and provides broad and efficient protection in vaccinated animals.
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.
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.In this study, the authors report a single cycle-replicating SARS-CoV-2 vaccine candidate virus (ΔEM) and show that it induces spike-specific IgA and CD8+ T cells targeting spike and nucleocapsid proteins and provides broad and efficient protection in vaccinated animals.
ArticleNumber 4453
Author Kuroda, Makoto
Uraki, Ryuta
Kawaoka, Yoshihiro
Babujee, Lavanya
Kim, Taksoo
Spyra, Sam
Yamayoshi, Seiya
Dahn, Randall
Halfmann, Peter J.
Armbrust, Tammy A.
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Snippet 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...
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...
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SubjectTerms 631/1647/334/1874/1535
631/326/590/1867
631/326/596/4130
Animals
Antibodies, Viral - immunology
CD8 antigen
CD8-Positive T-Lymphocytes - immunology
Coronavirus Envelope Proteins
COVID-19
COVID-19 - immunology
COVID-19 - prevention & control
COVID-19 - virology
COVID-19 Vaccines - administration & dosage
COVID-19 Vaccines - genetics
COVID-19 Vaccines - immunology
Cricetinae
Female
Hamsters
Humanities and Social Sciences
Humans
Immunization
Immunization, Secondary
Immunoglobulin A
Lymphocytes
Lymphocytes T
Membranes
Mesocricetus
mRNA
multidisciplinary
Nucleocapsids
Open reading frames
Open Reading Frames - genetics
Proteins
SARS-CoV-2 - genetics
SARS-CoV-2 - immunology
Science
Science (multidisciplinary)
Severe acute respiratory syndrome coronavirus 2
Spike Glycoprotein, Coronavirus - genetics
Spike Glycoprotein, Coronavirus - immunology
Structural proteins
Vaccination
Vaccines
Vaccines, Attenuated - administration & dosage
Vaccines, Attenuated - genetics
Vaccines, Attenuated - immunology
Viral diseases
Viruses
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Title SARS-CoV-2 virus lacking the envelope and membrane open-reading frames as a vaccine platform
URI https://link.springer.com/article/10.1038/s41467-025-59533-4
https://www.ncbi.nlm.nih.gov/pubmed/40360482
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