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bioRxiv · 10.1101/2021.03.26.437274

Mechanism of a COVID-19 nanoparticle vaccine candidate that elicits a broadly neutralizing antibody response to SARS-CoV-2 variants

Zhang, Y.-N.·Paynter, J.·Fourfouris, T.·Sou, C.·Ngo, T.·He, L.·Zhu, J.
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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 S2G{Delta}HR2 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), S2G{Delta}HR2 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. ONE-SENTENCE SUMMARYWith a well-defined mechanism, spike nanoparticle vaccines can effectively counter SARS-CoV-2 variants.

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Zhang, Y.-N., Paynter, J., Fourfouris, T., Sou, C., Ngo, T., He, L., Zhu, J.. 2021-03-27. Mechanism of a COVID-19 nanoparticle vaccine candidate that elicits a broadly neutralizing antibody response to SARS-CoV-2 variants. https://doi.org/10.1101/2021.03.26.437274

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