DeMarco Jennifer K, Royal Joshua M, Severson William E, Gabbard Jon D, Hume Steve, Morton Josh, Swope Kelsi, Simpson Carrie A, Shepherd John W, Bratcher Barry, Palmer Kenneth E, Pogue Gregory P
Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville, Louisville, KY 40202, USA.
Department of Microbiology and Immunology, University of Louisville, Louisville, KY 40202, USA.
Vaccines (Basel). 2021 Nov 17;9(11):1346. doi: 10.3390/vaccines9111346.
We developed a SARS-CoV-2 vaccine candidate (CoV-RBD121-NP) comprised of a tobacco mosaic virus-like nanoparticle conjugated to the receptor-binding domain of the spike glycoprotein of SARS-CoV-2 fused to a human IgG1 Fc domain. CoV-RBD121-NP elicits strong antibody responses in C57BL/6 mice and is stable for up to 12 months at 2-8 or 22-28 °C. Here, we showed that this vaccine induces a strong neutralizing antibody response in K18-hACE2 mice. Furthermore, we demonstrated that immunization protects mice from virus-associated mortality and symptomatic disease. Our data indicated that a sufficient pre-existing pool of neutralizing antibodies is required to restrict SARS-CoV-2 replication upon exposure and prevent induction of inflammatory mediators associated with severe disease. Finally, we identified a potential role for CXCL5 as a protective cytokine in SARS-CoV-2 infection. Our results suggested that disruption of the CXCL5 and CXCL1/2 axis may be important early components of the inflammatory dysregulation that is characteristic of severe cases of COVID-19.
我们研发了一种新型冠状病毒2型疫苗候选物（CoV-RBD121-NP），它由与新型冠状病毒刺突糖蛋白受体结合域偶联的烟草花叶病毒样纳米颗粒组成，并与人IgG1 Fc结构域融合。CoV-RBD121-NP在C57BL/6小鼠中引发强烈的抗体反应，在2-8℃或22-28℃下可稳定保存长达12个月。在此，我们表明这种疫苗在K18-hACE2小鼠中诱导出强烈的中和抗体反应。此外，我们证明免疫可保护小鼠免受病毒相关的死亡和症状性疾病。我们的数据表明，需要足够的预先存在的中和抗体库来限制新型冠状病毒暴露后的复制，并防止诱导与严重疾病相关的炎症介质。最后，我们确定了CXCL5作为新型冠状病毒感染中一种保护性细胞因子的潜在作用。我们的结果表明，CXCL5与CXCL1/2轴的破坏可能是新冠肺炎重症病例所特有的炎症失调的重要早期组成部分。
