Single-dose immunisation with a multimerised SARS-CoV-2 receptor binding domain (RBD) induces an enhanced and protective response in mice,FEBS Letters

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Single-dose immunisation with a multimerised SARS-CoV-2 receptor binding domain (RBD) induces an enhanced and protective response in mice
FEBS Letters ( IF 3.0 ) Pub Date : 2021-07-31 , DOI: 10.1002/1873-3468.14171
Ralf Salzer ₁ , Jordan J Clark ₂ , Marina Vaysburd ₁ , Veronica T Chang ₁ , Anna Albecka ₁ , Leo Kiss ₁ , Parul Sharma ₂ , Andres Gonzalez Llamazares ₁ , Anja Kipar _{2,

3} , Julian A Hiscox ₂ , Andrew Owen ₄ , A Radu Aricescu ₁ , James P Stewart ₂ , Leo C James ₁ , Jan Löwe ₁

Affiliation

The COVID-19 pandemic, caused by the SARS-CoV-2 coronavirus, has triggered a worldwide health emergency. Here, we show that ferritin-like Dps from hyperthermophilic Sulfolobus islandicus, covalently coupled with SARS-CoV-2 antigens via the SpyCatcher system, forms stable multivalent dodecameric vaccine nanoparticles that remain intact even after lyophilisation. Immunisation experiments in mice demonstrated that the SARS-CoV-2 receptor binding domain (RBD) coupled to Dps (RBD-S-Dps) elicited a higher antibody titre and an enhanced neutralising antibody response compared to monomeric RBD. A single immunisation with RBD-S-Dps completely protected hACE2-expressing mice from serious illness and led to viral clearance from the lungs upon SARS-CoV-2 infection. Our data highlight that multimerised SARS-CoV-2 subunit vaccines are a highly efficacious modality, particularly when combined with an ultra-stable scaffold.

中文翻译：

使用多聚化 SARS-CoV-2 受体结合域 (RBD) 进行单剂量免疫可诱导小鼠产生增强的保护性反应

由 SARS-CoV-2 冠状病毒引起的 COVID-19 大流行引发了全球卫生紧急情况。在这里，我们展示了来自超嗜热岛状硫化叶菌的铁蛋白样 Dps，通过SpyCatcher 系统与 SARS-CoV-2 抗原共价偶联，形成稳定的多价十二聚体疫苗纳米颗粒，即使在冻干后仍保持完整。小鼠免疫实验表明，与单体 RBD 相比，与 Dps (RBD-S-Dps) 偶联的 SARS-CoV-2 受体结合域 (RBD) 能引发更高的抗体滴度和增强的中和抗体反应。 RBD-S-Dps 的单次免疫完全保护表达 hACE2 的小鼠免受严重疾病的影响，并导致 SARS-CoV-2 感染后病毒从肺部清除。我们的数据强调，多聚 SARS-CoV-2 亚单位疫苗是一种非常有效的方式，特别是与超稳定支架结合使用时。

更新日期：2021-09-27

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