RT Journal Article
SR Electronic
T1 Self-assembling nanoparticles presenting receptor binding domain and stabilized spike as next-generation COVID-19 vaccines
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.09.14.296715
DO 10.1101/2020.09.14.296715
A1 Linling He
A1 Xiaohe Lin
A1 Ying Wang
A1 Ciril Abraham
A1 Cindy Sou
A1 Timothy Ngo
A1 Yi Zhang
A1 Ian A. Wilson
A1 Jiang Zhu
YR 2020
UL http://biorxiv.org/content/early/2020/09/14/2020.09.14.296715.abstract
AB We present a comprehensive vaccine strategy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by combining antigen optimization and nanoparticle display. We first developed a receptor binding domain (RBD)-specific antibody column for purification and displayed the RBD on self-assembling protein nanoparticles (SApNPs) using the SpyTag/SpyCatcher system. We then identified the heptad repeat 2 (HR2) stalk as a major cause of spike metastability, designed an HR2-deleted glycine-capped spike (S2GΔHR2), and displayed S2GΔHR2 on three SApNPs with high yield, purity, and antigenicity. Compared to the RBD, the RBD-ferritin SApNP elicited a more potent murine neutralizing antibody (NAb) response on par with the spike. S2GΔHR2 elicited two-fold-higher NAb titers than the proline-capped spike (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 next-generation vaccine candidate to battle the COVID-19 pandemic.ONE-SENTENCE SUMMARY The receptor binding domain and stabilized SARS-CoV-2 spike were displayed on nanoparticles as vaccine antigens and elicited potent immune responses.Competing Interest StatementThe authors have declared no competing interest.