Multivalent S2 Subunit Vaccines Provide Broad Protection Against Clade 1 Sarbecoviruses in Female Mice

Overview

Journal Nat Commun

Specialty Biology

Date 2025 Jan 8

PMID 39774966

Authors

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

Affiliations

Soon will be listed here.

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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