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He L , Lin X , Wang Y , Abraham C , Sou C , Ngo T , Zhang Y , Wilson IA , Zhu J
Single-component, self-assembling, protein nanoparticles presenting the receptor binding domain and stabilized spike as SARS-CoV-2 vaccine candidates
Sci Adv. 2021 Mar;7(12)
PMID: 33741598    PMCID: PMC7978432    URL: https://www.ncbi.nlm.nih.gov/pubmed/33741598
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Vaccination against SARS-CoV-2 provides an effective tool to combat the COVID-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 (S2GΔHR2), and displayed S2GΔHR2 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). S2GΔHR2 elicited twofold higher NAb titers than S2P, while S2GΔHR2 SApNPs derived from multilayered E2p and I3-01v9 60-mers elicited up to 10-fold higher NAb titers. The S2GΔHR2-presenting I3-01v9 SApNP also induced critically needed T cell immunity, thereby providing a promising vaccine candidate.
2375-2548 He, Linling Orcid: 0000-0001-8846-5352 Lin, Xiaohe Wang, Ying Abraham, Ciril Sou, Cindy Ngo, Timothy Zhang, Yi Wilson, Ian A Orcid: 0000-0002-6469-2419 Zhu, Jiang Orcid: 0000-0003-0259-7157 Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States Sci Adv. 2021 Mar 19;7(12):eabf1591. doi: 10.1126/sciadv.abf1591. Print 2021 Mar.