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Mechanism of a COVID-19 nanoparticle vaccine candidate that elicits a broadly neutralizing antibody response to SARS-CoV-2 variants
Zhang, Yi-Nan Paynter, Jennifer Sou, Cindy Fourfouris, Tatiana Abraham, Ciril Ngo, Timothy Zhang, Yi He, Linling Zhu, Jiang
Zhang, Yi-Nan
Paynter, Jennifer
Sou, Cindy
Fourfouris, Tatiana
Abraham, Ciril
Ngo, Timothy
Zhang, Yi
He, Linling
Zhu, Jiang
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Pre-print
Date
2021-09-09
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Microbiology and Immunology
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https://doi.org/10.1101/2021.03.26.437274
Abstract
Vaccines that induce potent neutralizing antibody (NAb) responses against emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are essential for combating the coronavirus disease 2019 (COVID-19) pandemic. We demonstrated that mouse plasma induced by self-assembling protein nanoparticles (SApNPs) that present 20 rationally designed S2GΔHR2 spikes of the ancestral Wuhan-Hu-1 strain can neutralize the B.1.1.7, B.1.351, P.1, and B.1.617 variants with the same potency. The adjuvant effect on vaccine-induced immunity was investigated by testing 16 formulations for the multilayered I3-01v9 SApNP. Using single-cell sorting, monoclonal antibodies (mAbs) with diverse neutralization breadth and potency were isolated from mice immunized with the receptor binding domain (RBD), S2GΔHR2 spike, and SApNP vaccines. The mechanism of vaccine-induced immunity was examined in mice. Compared with the soluble spike, the I3-01v9 SApNP showed 6-fold longer retention, 4-fold greater presentation on follicular dendritic cell dendrites, and 5-fold stronger germinal center reactions in lymph node follicles.
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