Emily
Editor, Senior Moderator
I'd call this gain-of-function. A new variant was created that resists the immunity we currently have. I don't think this was done in a BSL-4 lab.
https://www.biorxiv.org/content/10.1101/2020.12.28.424451v1.full
SARS-CoV-2 escape in vitro from a highly neutralizing COVID-19 convalescent plasma
Emanuele Andreano, Giulia Piccini, Danilo Licastro, Lorenzo Casalino, Nicole V. Johnson, Ida Paciello, Simeone Dal Monego, Elisa Pantano, Noemi Manganaro, Alessandro Manenti, Rachele Manna, Elisa Casa, Inesa Hyseni, Linda Benincasa, Emanuele Montomoli, Rommie E. Amaro, Jason S. McLellan, Rino Rappuoli
bioRxiv 2020.12.28.424451; doi: https://doi.org/10.1101/2020.12.28.424451 This article is a preprint and has not been certified by peer review [what does this mean?].
ABSTRACT
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.
https://www.biorxiv.org/content/10.1101/2020.12.28.424451v1.full
SARS-CoV-2 escape in vitro from a highly neutralizing COVID-19 convalescent plasma
Emanuele Andreano, Giulia Piccini, Danilo Licastro, Lorenzo Casalino, Nicole V. Johnson, Ida Paciello, Simeone Dal Monego, Elisa Pantano, Noemi Manganaro, Alessandro Manenti, Rachele Manna, Elisa Casa, Inesa Hyseni, Linda Benincasa, Emanuele Montomoli, Rommie E. Amaro, Jason S. McLellan, Rino Rappuoli
bioRxiv 2020.12.28.424451; doi: https://doi.org/10.1101/2020.12.28.424451 This article is a preprint and has not been certified by peer review [what does this mean?].
ABSTRACT
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.
