SARS-CoV-2 ferritin nanoparticle vaccines produce hyperimmune equine sera with broad sarbecovirus activity

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

doi:10.1016/j.isci.2024.110624

SARS-CoV-2 ferritin nanoparticle vaccines produce hyperimmune equine sera with broad sarbecovirus activity

iScience. 2024 Aug 23;27(10):110624. doi: 10.1016/j.isci.2024.110624. eCollection 2024 Oct 18.

Authors

Elizabeth J Martinez^{1

2}, William C Chang^{1

2}, Wei-Hung 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 Soman³, Caitlin Kuklis³, Letzibeth Mendez-Rivera^{2

4}, Vincent Dussupt^{2

4}, Jocelyn King^{1

2}, Courtney Corbett^{1

2}, Sandra V Mayer^{1

2}, Aldon Fernandes⁵, Kripa Murzello⁶, Tres Cookenham⁶, Janine Hvizdos⁶, Larry Kummer⁶, Tricia Hart⁶, Kathleen Lanzer⁶, Julian Gambacurta⁶, Matthew Reagan⁶, Debbie Duso⁶, Sandhya Vasan^{1

2}, Natalie D Collins¹, Nelson L Michael⁷, Shelly J Krebs⁴, Gregory D Gromowski³, Kayvon Modjarrad¹, John Kaundinya⁸, M Gordon Joyce^{1

2}

Affiliations

¹ Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
² Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
³ Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
⁴ U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
⁵ Bharat Serums and Vaccines Ltd., Mumbai, Maharashtra, India.
⁶ Trudeau Institute, Saranac Lake, NY, USA.
⁷ Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
⁸ BSV Biosciences, Inc., Morgan Hill, CA, USA.

Abstract

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.