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SARS-CoV-2 escape from a highly neutralizing COVID-19 convalescent plasma

Proceedings of the National Academy of Sciences - PNAS, 2021-09, Vol.118 (36) [Peer Reviewed Journal]

Copyright National Academy of Sciences Sep 7, 2021 ;Copyright © 2021 the Author(s). Published by PNAS. 2021 ;ISSN: 0027-8424 ;EISSN: 1091-6490 ;DOI: 10.1073/pnas.2103154118 ;PMID: 34417349

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Title:
SARS-CoV-2 escape from a highly neutralizing COVID-19 convalescent plasma
Author: Andreano, Emanuele ; Piccini, Giulia ; Licastro, Danilo ; Casalino, Lorenzo ; Johnson, Nicole V. ; Paciello, Ida ; Dal Monego, Simeone ; Pantano, Elisa ; Manganaro, Noemi ; Manenti, Alessandro ; Manna, Rachele ; Casa, Elisa ; Hyseni, Inesa ; Benincasa, Linda ; Montomoli, Emanuele ; Amaro, Rommie E. ; McLellan, Jason S. ; Rappuoli, Rino
Subjects: Antibodies ; Binding ; Biological Sciences ; Computer applications ; Coronaviruses ; COVID-19 ; Deletion ; Domains ; Glycan ; Immune response ; Immune system ; Insertion ; Neutralization ; Neutralizing ; Plasma ; Severe acute respiratory syndrome ; Severe acute respiratory syndrome coronavirus 2 ; Stability ; Vaccines ; Viral diseases ; Viruses
Is Part Of: Proceedings of the National Academy of Sciences - PNAS, 2021-09, Vol.118 (36)
Description: Significance This work shows that, under strong immune pressure, SARS-CoV-2 can use mutations in both the N-terminal domain and the receptor-binding domain to escape potent polyclonal neutralizing responses. Indeed, after a long period under immune selective pressure, SARS-CoV-2 evolved to evade the immunity of a potent polyclonal serum from a COVID-19 convalescent donor. Only three mutations were sufficient to generate this escape variant. The new virus was resistant to 70% of the neutralizing antibodies tested and had a decreased susceptibility to all convalescent sera. Our data predict that, as the immunity in the population increases, following infection and vaccination, new variants will emerge, and therefore vaccines and monoclonal antibodies need to be developed to address them. To investigate the evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the immune population, we coincupi bated the authentic virus with a highly neutralizing plasma from a COVID-19 convalescent patient. The plasma fully neutralized the virus for seven passages, but, after 45 d, 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, South Africa, Brazil, and Japan 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.
Publisher: Washington: National Academy of Sciences
Language: English
Identifier: ISSN: 0027-8424
EISSN: 1091-6490
DOI: 10.1073/pnas.2103154118
PMID: 34417349
Source: Geneva Foundation Free Medical Journals at publisher websites
PubMed Central

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SARS-CoV-2 escape from a highly neutralizing COVID-19 convalescent plasma

Copyright National Academy of Sciences Sep 7, 2021 ;Copyright © 2021 the Author(s). Published by PNAS. 2021 ;ISSN: 0027-8424 ;EISSN: 1091-6490 ;DOI: 10.1073/pnas.2103154118 ;PMID: 34417349

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