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SARS-CoV-2 escape from a highly neutralizing COVID-19 convalescent plasma.
Proc Natl Acad Sci U S A. 2021 09 07; 118(36)PN

Abstract

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.

Authors+Show Affiliations

Monoclonal Antibody Discovery Lab, Fondazione Toscana Life Sciences, 53100 Siena, Italy.VisMederi S.r.l., 53100 Siena, Italy.ARGO Open Lab Platform for Genome Sequencing, 34149 Trieste, Italy.Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093.Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712.Monoclonal Antibody Discovery Lab, Fondazione Toscana Life Sciences, 53100 Siena, Italy.ARGO Open Lab Platform for Genome Sequencing, 34149 Trieste, Italy.Monoclonal Antibody Discovery Lab, Fondazione Toscana Life Sciences, 53100 Siena, Italy.Monoclonal Antibody Discovery Lab, Fondazione Toscana Life Sciences, 53100 Siena, Italy.VisMederi S.r.l., 53100 Siena, Italy. VisMederi Research S.r.l., 53100 Siena, Italy.VisMederi S.r.l., 53100 Siena, Italy.VisMederi S.r.l., 53100 Siena, Italy. VisMederi Research S.r.l., 53100 Siena, Italy.VisMederi S.r.l., 53100 Siena, Italy. VisMederi Research S.r.l., 53100 Siena, Italy.VisMederi Research S.r.l., 53100 Siena, Italy.VisMederi S.r.l., 53100 Siena, Italy. VisMederi Research S.r.l., 53100 Siena, Italy. Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy.Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093.Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712.Monoclonal Antibody Discovery Lab, Fondazione Toscana Life Sciences, 53100 Siena, Italy; rino.r.rappuoli@gsk.com. Faculty of Medicine, Imperial College, SW7 2DD London, United Kingdom.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

34417349

Citation

Andreano, Emanuele, et al. "SARS-CoV-2 Escape From a Highly Neutralizing COVID-19 Convalescent Plasma." Proceedings of the National Academy of Sciences of the United States of America, vol. 118, no. 36, 2021.
Andreano E, Piccini G, Licastro D, et al. SARS-CoV-2 escape from a highly neutralizing COVID-19 convalescent plasma. Proc Natl Acad Sci U S A. 2021;118(36).
Andreano, E., Piccini, G., Licastro, D., Casalino, L., Johnson, N. V., Paciello, I., Dal Monego, S., Pantano, E., Manganaro, N., Manenti, A., Manna, R., Casa, E., Hyseni, I., Benincasa, L., Montomoli, E., Amaro, R. E., McLellan, J. S., & Rappuoli, R. (2021). SARS-CoV-2 escape from a highly neutralizing COVID-19 convalescent plasma. Proceedings of the National Academy of Sciences of the United States of America, 118(36). https://doi.org/10.1073/pnas.2103154118
Andreano E, et al. SARS-CoV-2 Escape From a Highly Neutralizing COVID-19 Convalescent Plasma. Proc Natl Acad Sci U S A. 2021 09 7;118(36) PubMed PMID: 34417349.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - SARS-CoV-2 escape from a highly neutralizing COVID-19 convalescent plasma. AU - Andreano,Emanuele, AU - Piccini,Giulia, AU - Licastro,Danilo, AU - Casalino,Lorenzo, AU - Johnson,Nicole V, AU - Paciello,Ida, AU - Dal Monego,Simeone, AU - Pantano,Elisa, AU - Manganaro,Noemi, AU - Manenti,Alessandro, AU - Manna,Rachele, AU - Casa,Elisa, AU - Hyseni,Inesa, AU - Benincasa,Linda, AU - Montomoli,Emanuele, AU - Amaro,Rommie E, AU - McLellan,Jason S, AU - Rappuoli,Rino, PY - 2021/8/21/entrez PY - 2021/8/22/pubmed PY - 2021/9/1/medline KW - COVID-19 KW - SARS-CoV-2 KW - antibody response KW - emerging variants KW - immune evasion JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc Natl Acad Sci U S A VL - 118 IS - 36 N2 - 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. SN - 1091-6490 UR - https://www.unboundmedicine.com/medline/citation/34417349/SARS_CoV_2_escape_from_a_highly_neutralizing_COVID_19_convalescent_plasma_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=34417349 DB - PRIME DP - Unbound Medicine ER -