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bioRxiv · 10.1101/2020.09.14.296715

Self-assembling nanoparticles presenting receptor binding domain and stabilized spike as next-generation COVID-19 vaccines

He, L.·Lin, X.·Wang, Y.·Abraham, C.·Sou, C.·Ngo, T.·Zhang, Y.·Wilson, I. A.·Zhu, J.
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Abstract

Vaccination against SARS-CoV-2 provides an effective tool to combat the COIVD-19 pandemic. Here, we combined antigen optimization and nanoparticle display to develop vaccine candidates for SARS-CoV-2. We first displayed the receptor-binding domain (RBD) on three self-assembling protein nanoparticle (SApNP) platforms using the SpyTag/SpyCatcher system. We then identified heptad repeat 2 (HR2) in S2 as the cause of spike metastability, designed an HR2-deleted glycine-capped spike (S2G{Delta}HR2), and displayed S2G{Delta}HR2 on SApNPs. An antibody column specific for the RBD enabled tag-free vaccine purification. In mice, the 24-meric RBD-ferritin SApNP elicited a more potent neutralizing antibody (NAb) response than the RBD alone and the spike with two stabilizing proline mutations in S2 (S2P). S2G{Delta}HR2 elicited two-fold-higher NAb titers than S2P, while S2G{Delta}HR2 SApNPs derived from multilayered E2p and I3-01v9 60-mers elicited up to 10-fold higher NAb titers. The S2G{Delta}HR2-presenting I3-01v9 SApNP also induced critically needed T-cell immunity, thereby providing a promising vaccine candidate. ONE-SENTENCE SUMMARYThe SARS-CoV-2 receptor binding domain and S2G{Delta}HR2 spike elicited potent immune responses when displayed on protein nanoparticles as vaccine candidates.

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He, L., Lin, X., Wang, Y., Abraham, C., Sou, C., Ngo, T., Zhang, Y., Wilson, I. A., Zhu, J.. 2020-09-14. Self-assembling nanoparticles presenting receptor binding domain and stabilized spike as next-generation COVID-19 vaccines. https://doi.org/10.1101/2020.09.14.296715

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