TY - JOUR T1 - SARS-CoV-2 escape <em>in vitro</em> from a highly neutralizing COVID-19 convalescent plasma JF - bioRxiv DO - 10.1101/2020.12.28.424451 SP - 2020.12.28.424451 AU - Emanuele Andreano AU - Giulia Piccini AU - Danilo Licastro AU - Lorenzo Casalino AU - Nicole V. Johnson AU - Ida Paciello AU - Simeone Dal Monego AU - Elisa Pantano AU - Noemi Manganaro AU - Alessandro Manenti AU - Rachele Manna AU - Elisa Casa AU - Inesa Hyseni AU - Linda Benincasa AU - Emanuele Montomoli AU - Rommie E. Amaro AU - Jason S. McLellan AU - Rino Rappuoli Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/12/28/2020.12.28.424451.abstract N2 - To investigate the evolution of SARS-CoV-2 in the immune population, we co-incubated authentic virus with a highly neutralizing plasma from a COVID-19 convalescent patient. The plasma fully neutralized the virus for 7 passages, but after 45 days, the deletion of F140 in the spike N-terminal domain (NTD) N3 loop led to partial breakthrough. At day 73, an E484K substitution in the receptor-binding domain (RBD) occurred, followed at day 80 by an insertion in the NTD N5 loop containing a new glycan sequon, which generated a variant completely resistant to plasma neutralization. Computational modeling predicts that the deletion and insertion in loops N3 and N5 prevent binding of neutralizing antibodies. The recent emergence in the United Kingdom and South Africa of natural variants with similar changes suggests that SARS-CoV-2 has the potential to escape an effective immune response and that vaccines and antibodies able to control emerging variants should be developed.One Sentence Summary Three mutations allowed SARS-CoV-2 to evade the polyclonal antibody response of a highly neutralizing COVID-19 convalescent plasma.Competing Interest StatementRino Rappuoli is an employee of GSK group of companies. Emanuele Andreano, Ida Paciello, Elisa Pantano, Noemi Manganaro and Rino Rappuoli are listed as inventors of full-length human monoclonal antibodies described in Italian patent applications n. 102020000015754 filed on June 30th 2020 and 102020000018955 filed on August 3rd 2020. ER -