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

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.