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

Salzer, R.; Clark, J. J.; Vaysburd, M.; Chang, V. T.; Albecka-Moreau, A.; Kiss, L.; Sharma, P.; Gonzalez Llamazares, A.; Kipar, A.; Hiscox, J. A.; Owen, A.; Aricescu, A. R.; Stewart, J. P.; James, L. C.; Lowe, J.

doi:10.1101/2021.05.18.444622

bioRxiv · 10.1101/2021.05.18.444622

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

Salzer, R.·Clark, J. J.·Vaysburd, M.·Chang, V. T.·Albecka-Moreau, A.·Kiss, L.·Sharma, P.·Gonzalez Llamazares, A.·Kipar, A.·Hiscox, J. A.·Owen, A.·Aricescu, A. R.·Stewart, J. P.·James, L. C.·Lowe, J.

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Abstract

The COVID-19 pandemic, caused by the SARS-CoV-2 coronavirus, has triggered a worldwide health emergency. So far, several different types of vaccines have shown strong efficacy. However, both the emergence of new SARS-CoV-2 variants and the need to vaccinate a large fraction of the worlds population necessitate the development of alternative vaccines, especially those that are simple and easy to store, transport and administer. Here, we showed that ferritin-like Dps protein from hyperthermophilic Sulfolobus islandicus can be covalently coupled with different SARS-CoV-2 antigens via the SpyCatcher system, to form extremely stable and defined 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) shows particular promise as it elicited a higher antibody titre and an enhanced neutralising antibody response compared to the monomeric RBD. Furthermore, we showed that a single immunisation with the multivalent RBD-S-Dps completely protected hACE2-expressing mice from serious illness and led to efficient 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.

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Salzer, R., Clark, J. J., Vaysburd, M., Chang, V. T., Albecka-Moreau, A., Kiss, L., Sharma, P., Gonzalez Llamazares, A., Kipar, A., Hiscox, J. A., Owen, A., Aricescu, A. R., Stewart, J. P., James, L. C., Lowe, J.. 2021-05-18. Single-dose immunisation with a multimerised SARS-CoV-2 receptor binding domain (RBD) induces an enhanced and protective response in mice. https://doi.org/10.1101/2021.05.18.444622

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