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Nat Commun
. 2025 Jan 7;16(1):462.
doi: 10.1038/s41467-025-55824-y. Multivalent S2 subunit vaccines provide broad protection against Clade 1 sarbecoviruses in female mice
Peter J Halfmann # 1 , Raj S Patel # 2 , Kathryn Loeffler 3 , Atsuhiro Yasuhara 4 , Lee-Ann Van De Velde 5 , Jie E Yang 6 7 8 , Jordan Chervin 4 , Chloe Troxell 4 , Min Huang 4 , Naiying Zheng 4 , Elizabeth R Wright 6 7 8 , Paul G Thomas 5 , Patrick C Wilson 4 , Yoshihiro Kawaoka 9 10 11 12 , Ravi S Kane 13 14
Affiliations
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.
. 2025 Jan 7;16(1):462.
doi: 10.1038/s41467-025-55824-y. Multivalent S2 subunit vaccines provide broad protection against Clade 1 sarbecoviruses in female mice
Peter J Halfmann # 1 , Raj S Patel # 2 , Kathryn Loeffler 3 , Atsuhiro Yasuhara 4 , Lee-Ann Van De Velde 5 , Jie E Yang 6 7 8 , Jordan Chervin 4 , Chloe Troxell 4 , Min Huang 4 , Naiying Zheng 4 , Elizabeth R Wright 6 7 8 , Paul G Thomas 5 , Patrick C Wilson 4 , Yoshihiro Kawaoka 9 10 11 12 , Ravi S Kane 13 14
Affiliations
- PMID: 39774966
- PMCID: PMC11706982
- DOI: 10.1038/s41467-025-55824-y
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.