Martinez Elizabeth J, Chang William C, Chen Wei-Hung, Hajduczki Agnes, Thomas Paul V, Jensen Jaime L, Choe Misook, Sankhala Rajeshwer S, Peterson Caroline E, Rees Phyllis A, Kimner Jordan, Soman Sandrine, Kuklis Caitlin, Mendez-Rivera Letzibeth, Dussupt Vincent, King Jocelyn, Corbett Courtney, Mayer Sandra V, Fernandes Aldon, Murzello Kripa, Cookenham Tres, Hvizdos Janine, Kummer Larry, Hart Tricia, Lanzer Kathleen, Gambacurta Julian, Reagan Matthew, Duso Debbie, Vasan Sandhya, Collins Natalie D, Michael Nelson L, Krebs Shelly J, Gromowski Gregory D, Modjarrad Kayvon, Kaundinya John, Joyce M Gordon
Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
iScience. 2024 Aug 23;27(10):110624. doi: 10.1016/j.isci.2024.110624. eCollection 2024 Oct 18.
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.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）变异株（VoC）的迅速出现以及未来人畜共患的沙贝病毒溢出的威胁，凸显了开发具有广泛保护作用的下一代疫苗和治疗方法的必要性。我们在马模型中使用了SARS-CoV-2刺突铁蛋白纳米颗粒（SpFN）和SARS-CoV-2受体结合域铁蛋白纳米颗粒（RFN）免疫原，以诱导产生超免疫血清，并评估其对沙贝病毒的中和及保护能力。免疫动物迅速产生了能有效中和SARS-CoV-2变异株和SARS-CoV-1假病毒的血清，以及能有效结合沙贝病毒1b、1a、2、3和4分支受体结合域的血清。纯化的马多克隆IgG在K18-hACE2转基因小鼠模型中对奥密克戎XBB.1.5病毒提供了保护。这些结果表明，基于SARS-CoV-2的纳米颗粒疫苗能够在马模型中迅速产生广泛的、具有保护性的沙贝病毒反应，并且马血清对新出现的SARS-CoV-2变异株和多种沙贝病毒具有治疗潜力，这为单克隆抗体免疫疗法提供了一种可能的替代或补充。
