| Title | Multivalent S2 subunit vaccines provide broad protection against Clade 1 sarbecoviruses in female mice. |
| Publication Type | Journal Article |
| Year of Publication | 2025 |
| Authors | Halfmann PJ, Patel RS, Loeffler K, Yasuhara A, Van De Velde L-A, Yang JE, Chervin J, Troxell C, Huang M, Zheng N, Wright ER, Thomas PG, Wilson PC, Kawaoka Y, Kane RS |
| Journal | Nat Commun |
| Volume | 16 |
| Issue | 1 |
| Pagination | 462 |
| Date Published | 2025 Jan 07 |
| ISSN | 2041-1723 |
| Keywords | Animals, Antibodies, Neutralizing, Antibodies, Viral, COVID-19, COVID-19 Vaccines, Female, Humans, Mice, Mice, Knockout, Mice, Transgenic, Receptors, IgG, SARS-CoV-2, Spike Glycoprotein, Coronavirus, Vaccines, Subunit |
| 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. |
| DOI | 10.1038/s41467-025-55824-y |
| Custom 1 | |
| Alternate Journal | Nat Commun |
| PubMed ID | 39774966 |
| PubMed Central ID | PMC11706982 |
| Grant List | P01AI165077 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) / |