Multivalent S2 subunit vaccines provide broad protection against Clade 1 sarbecoviruses in female mice
Abstract The continuing emergence of immune evasive SARS-CoV-2 variants and the previous SARS-CoV-1 outbreak collectively underscore the need for broadly protective sarbecovirus vaccines. Targeting the conserved S2 subunit of SARS-CoV-2 is a particularly promising approach to elicit broad protection...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-55824-y |
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| author | Peter J. Halfmann Raj S. Patel Kathryn Loeffler Atsuhiro Yasuhara Lee-Ann Van De Velde Jie E. Yang Jordan Chervin Chloe Troxell Min Huang Naiying Zheng Elizabeth R. Wright Paul G. Thomas Patrick C. Wilson Yoshihiro Kawaoka Ravi S. Kane |
| author_facet | Peter J. Halfmann Raj S. Patel Kathryn Loeffler Atsuhiro Yasuhara Lee-Ann Van De Velde Jie E. Yang Jordan Chervin Chloe Troxell Min Huang Naiying Zheng Elizabeth R. Wright Paul G. Thomas Patrick C. Wilson Yoshihiro Kawaoka Ravi S. Kane |
| author_sort | Peter J. Halfmann |
| collection | DOAJ |
| description | Abstract The continuing emergence of immune evasive SARS-CoV-2 variants and the previous SARS-CoV-1 outbreak collectively underscore the need for broadly protective sarbecovirus vaccines. Targeting the conserved S2 subunit of SARS-CoV-2 is a particularly promising approach to elicit broad protection. Here, we describe a nanoparticle vaccine displaying multiple copies of the SARS-CoV-1 S2 subunit. This vaccine alone, or as a cocktail with a SARS-CoV-2 S2 subunit vaccine, protects female transgenic K18-hACE2 mice from challenges with Omicron subvariant XBB as well as several sarbecoviruses identified as having pandemic potential including the bat sarbecovirus WIV1, BANAL-236, and a pangolin sarbecovirus. Challenge studies in female Fc-γ receptor knockout mice reveal that antibody-based cellular effector mechanisms play a role in protection elicited by these vaccines. These results demonstrate that our S2-based vaccines provide broad protection against clade 1 sarbecoviruses and offer insight into the mechanistic basis for protection. |
| format | Article |
| id | doaj-art-a1c9e347c3544ac09d8c2f9779c99ae5 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-a1c9e347c3544ac09d8c2f9779c99ae52025-01-12T12:30:59ZengNature PortfolioNature Communications2041-17232025-01-0116111710.1038/s41467-025-55824-yMultivalent S2 subunit vaccines provide broad protection against Clade 1 sarbecoviruses in female micePeter J. Halfmann0Raj S. Patel1Kathryn Loeffler2Atsuhiro Yasuhara3Lee-Ann Van De Velde4Jie E. Yang5Jordan Chervin6Chloe Troxell7Min Huang8Naiying Zheng9Elizabeth R. Wright10Paul G. Thomas11Patrick C. Wilson12Yoshihiro Kawaoka13Ravi S. Kane14Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of WisconsinWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of TechnologySchool of Chemical & Biomolecular Engineering, Georgia Institute of TechnologyDrukier Institute for Children’s Health, Department of Pediatrics, Weill Cornell MedicineDepartment of Immunology, St. Jude Children’s Research HospitalDepartment of Biochemistry, University of WisconsinDrukier Institute for Children’s Health, Department of Pediatrics, Weill Cornell MedicineDrukier Institute for Children’s Health, Department of Pediatrics, Weill Cornell MedicineDrukier Institute for Children’s Health, Department of Pediatrics, Weill Cornell MedicineDrukier Institute for Children’s Health, Department of Pediatrics, Weill Cornell MedicineDepartment of Biochemistry, University of WisconsinDepartment of Immunology, St. Jude Children’s Research HospitalDrukier Institute for Children’s Health, Department of Pediatrics, Weill Cornell MedicineInfluenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of WisconsinWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of TechnologyAbstract The continuing emergence of immune evasive SARS-CoV-2 variants and the previous SARS-CoV-1 outbreak collectively underscore the need for broadly protective sarbecovirus vaccines. Targeting the conserved S2 subunit of SARS-CoV-2 is a particularly promising approach to elicit broad protection. Here, we describe a nanoparticle vaccine displaying multiple copies of the SARS-CoV-1 S2 subunit. This vaccine alone, or as a cocktail with a SARS-CoV-2 S2 subunit vaccine, protects female transgenic K18-hACE2 mice from challenges with Omicron subvariant XBB as well as several sarbecoviruses identified as having pandemic potential including the bat sarbecovirus WIV1, BANAL-236, and a pangolin sarbecovirus. Challenge studies in female Fc-γ receptor knockout mice reveal that antibody-based cellular effector mechanisms play a role in protection elicited by these vaccines. These results demonstrate that our S2-based vaccines provide broad protection against clade 1 sarbecoviruses and offer insight into the mechanistic basis for protection.https://doi.org/10.1038/s41467-025-55824-y |
| spellingShingle | Peter J. Halfmann Raj S. Patel Kathryn Loeffler Atsuhiro Yasuhara Lee-Ann Van De Velde Jie E. Yang Jordan Chervin Chloe Troxell Min Huang Naiying Zheng Elizabeth R. Wright Paul G. Thomas Patrick C. Wilson Yoshihiro Kawaoka Ravi S. Kane Multivalent S2 subunit vaccines provide broad protection against Clade 1 sarbecoviruses in female mice Nature Communications |
| title | Multivalent S2 subunit vaccines provide broad protection against Clade 1 sarbecoviruses in female mice |
| title_full | Multivalent S2 subunit vaccines provide broad protection against Clade 1 sarbecoviruses in female mice |
| title_fullStr | Multivalent S2 subunit vaccines provide broad protection against Clade 1 sarbecoviruses in female mice |
| title_full_unstemmed | Multivalent S2 subunit vaccines provide broad protection against Clade 1 sarbecoviruses in female mice |
| title_short | Multivalent S2 subunit vaccines provide broad protection against Clade 1 sarbecoviruses in female mice |
| title_sort | multivalent s2 subunit vaccines provide broad protection against clade 1 sarbecoviruses in female mice |
| url | https://doi.org/10.1038/s41467-025-55824-y |
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