iScience


. 2024 Aug 23;27(10):110624.
doi: 10.1016/j.isci.2024.110624. eCollection 2024 Oct 18. SARS-CoV-2 ferritin nanoparticle vaccines produce hyperimmune equine sera with broad sarbecovirus activity

Elizabeth J Martinez 1 2 , William C Chang 1 2 , Wei-**** Chen 1 2 , Agnes Hajduczki 1 2 , Paul V Thomas 1 2 , Jaime L Jensen 1 2 , Misook Choe 1 2 , Rajeshwer S Sankhala 1 2 , Caroline E Peterson 1 2 , Phyllis A Rees 1 2 , Jordan Kimner 2 3 , Sandrine Soman 3 , Caitlin Kuklis 3 , Letzibeth Mendez-Rivera 2 4 , Vincent Dussupt 2 4 , Jocelyn King 1 2 , Courtney Corbett 1 2 , Sandra V Mayer 1 2 , Aldon Fernandes 5 , Kripa Murzello 6 , Tres Cookenham 6 , Janine Hvizdos 6 , Larry Kummer 6 , Tricia Hart 6 , Kathleen Lanzer 6 , Julian Gambacurta 6 , Matthew Reagan 6 , Debbie Duso 6 , Sandhya Vasan 1 2 , Natalie D Collins 1 , Nelson L Michael 7 , Shelly J Krebs 4 , Gregory D Gromowski 3 , Kayvon Modjarrad 1 , John Kaundinya 8 , M Gordon Joyce 1 2



AffiliationsAbstract

The rapid emergence of SARS-CoV-2 variants of concern (VoC) and the threat of future zoonotic sarbecovirus spillover emphasizes the need for broadly protective next-generation vaccines and therapeutics. We utilized SARS-CoV-2 spike ferritin nanoparticle (SpFN), and SARS-CoV-2 receptor binding domain ferritin nanoparticle (RFN) immunogens, in an equine model to elicit hyperimmune sera and evaluated its sarbecovirus neutralization and protection capacity. Immunized animals rapidly elicited sera with the potent neutralization of SARS-CoV-2 VoC, and SARS-CoV-1 pseudoviruses, and potent binding against receptor binding domains from sarbecovirus clades 1b, 1a, 2, 3, and 4. Purified equine polyclonal IgG provided protection against Omicron XBB.1.5 virus in the K18-hACE2 transgenic mouse model. These results suggest that SARS-CoV-2-based nanoparticle vaccines can rapidly produce a broad and protective sarbecovirus response in the equine model and that equine serum has therapeutic potential against emerging SARS-CoV-2 VoC and diverse sarbecoviruses, presenting a possible alternative or supplement to monoclonal antibody immunotherapies.

Keywords: Immunology; Virology.