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Nat Commun . Multivalent S2 subunit vaccines provide broad protection against Clade 1 sarbecoviruses in female mice

tetano

Editor, Senior Moderator
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[SUP] #[/SUP][SUP] 1 [/SUP], Raj S Patel[SUP] #[/SUP][SUP] 2 [/SUP], Kathryn Loeffler[SUP] 3 [/SUP], Atsuhiro Yasuhara[SUP] 4 [/SUP], Lee-Ann Van De Velde[SUP] 5 [/SUP], Jie E Yang[SUP] 6 7 8 [/SUP], Jordan Chervin[SUP] 4 [/SUP], Chloe Troxell[SUP] 4 [/SUP], Min Huang[SUP] 4 [/SUP], Naiying Zheng[SUP] 4 [/SUP], Elizabeth R Wright[SUP] 6 7 8 [/SUP], Paul G Thomas[SUP] 5 [/SUP], Patrick C Wilson[SUP] 4 [/SUP], Yoshihiro Kawaoka[SUP] 9 10 11 12 [/SUP], Ravi S Kane[SUP] 13 14 [/SUP]



Affiliations
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.


 
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