A public vaccine-induced human antibody protects against SARS-CoV-2 and emerging variants

Schmitz, A. J.; Turner, J. S.; Liu, Z.; Aziati, I. D.; Chen, R. E.; Joshi, A.; Bricker, T. L.; Darling, T. L.; Adelsberg, D. C.; Al Soussi, W. B.; Case, J. B.; Lei, T.; Thapa, M.; Amanat, F.; O'Halloran, J. A.; Shi, P.-Y.; Presti, R. M.; Krammer, F.; Bajic, G.; Whelan, S. P. J.; Diamond, M. S.; Boon, A. C. M.; Ellebedy, A. H.

doi:10.1101/2021.03.24.436864

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bioRxiv · 10.1101/2021.03.24.436864

A public vaccine-induced human antibody protects against SARS-CoV-2 and emerging variants

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Abstract

The emergence of antigenically distinct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with increased transmissibility is a public health threat. Some of these variants show substantial resistance to neutralization by SARS-CoV-2 infection- or vaccination-induced antibodies, which principally target the receptor binding domain (RBD) on the virus spike glycoprotein. Here, we describe 2C08, a SARS-CoV-2 mRNA vaccine-induced germinal center B cell-derived human monoclonal antibody that binds to the receptor binding motif within the RBD. 2C08 broadly neutralizes SARS-CoV-2 variants with remarkable potency and reduces lung inflammation, viral load, and morbidity in hamsters challenged with either an ancestral SARS-CoV-2 strain or a recent variant of concern. Clonal analysis identified 2C08-like public clonotypes among B cell clones responding to SARS-CoV-2 infection or vaccination in at least 20 out of 78 individuals. Thus, 2C08-like antibodies can be readily induced by SARS-CoV-2 vaccines and mitigate resistance by circulating variants of concern. One Sentence SummaryProtection against SARS-CoV-2 variants by a potently neutralizing vaccine-induced human monoclonal antibody.

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Schmitz, A. J., Turner, J. S., Liu, Z., Aziati, I. D., Chen, R. E., Joshi, A., Bricker, T. L., Darling, T. L., Adelsberg, D. C., Al Soussi, W. B., Case, J. B., Lei, T., Thapa, M., Amanat, F., O'Halloran, J. A., Shi, P.-Y., Presti, R. M., Krammer, F., Bajic, G., Whelan, S. P. J., Diamond, M. S., Boon, A. C. M., Ellebedy, A. H.. 2021-03-25. A public vaccine-induced human antibody protects against SARS-CoV-2 and emerging variants. https://doi.org/10.1101/2021.03.24.436864

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