In this article the authors identify four receptor-binding domain targeting antibodies from three early-outbreak convalescent donors with potent neutralizing activity against 23 variants including the B.1.1.7, B.1.351, P.1, B.1.429, B.1.526 and B.1.617 VOCs. Two antibodies are ultrapotent, with sub-nanomolar neutralization titers (IC50 0.3 to 11.1 ng/mL; IC80 1.5 to 34.5 ng/mL). Furthermore, the authors define the structural and functional determinants of binding for all four VOC-targeting antibodies and show that combinations of two antibodies decrease the in vitro generation of escape mutants, suggesting their potential in mitigating resistance development.
Wang L, Zhou T, Zhang Y, Yang ES, Schramm CA, Shi W, Pegu A, Oloniniyi OK, Henry AR, Darko S, Narpala SR, Hatcher C, Martinez DR, Tsybovsky Y, Phung E, Abiona OM, Antia A, Cale EM, Chang LA, Choe M, Corbett KS, Davis RL, DiPiazza AT, Gordon IJ, Helmold Hait S, Hermanus T, Kgagudi P, Laboune F, Leung K, Liu T, Mason RD, Nazzari AF, Novik L, O’Connell S, O’Dell S, Olia AS, Schmidt SD, Stephens T, Stringham CD, Talana CA, Teng IT, Wagner DA, Widge AT, Zhang B, Roederer M, Ledgerwood JE, Ruckwardt TJ, Gaudinski MR, Moore PL, Doria-Rose NA, Baric RS, Graham BS, McDermott AB, Douek DC, Kwong PD, Mascola JR, Sullivan NJ, Misasi J. Ultrapotent antibodies against diverse and highly transmissible SARS-CoV-2 variants. Science. 2021 Jul 1:eabh1766. doi: 10.1126/science.abh1766.