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

被引：212

作者：

Andreano, Emanuele ^{[1
]}

Piccini, Giulia ^{[2
]}

Licastro, Danilo ^{[3
]}

Casalino, Lorenzo ^{[4
]}

Johnson, Nicole, V ^{[5
]}

Paciello, Ida ^{[1
]}

Dal Monego, Simeone ^{[3
]}

Pantano, Elisa ^{[1
]}

Manganaro, Noemi ^{[1
]}

Manenti, Alessandro ^{[2
,6
]}

Manna, Rachele ^{[2
]}

Casa, Elisa ^{[2
,6
]}

Hyseni, Inesa ^{[2
,6
]}

Benincasa, Linda ^{[6
]}

Montomoli, Emanuele ^{[2
,6
,7
]}

Amaro, Rommie E. ^{[4
]}

McLellan, Jason S. ^{[5
]}

Rappuoli, Rino ^{[1
,8
]}

机构：

[1] Fdn Toscana Life Sci, Monoclonal Antibody Discovery Mad Lab, I-53100 Siena, Italy

[2] VisMederi Srl, I-53100 Siena, Italy

[3] ARGO Open Lab Platform Genome Sequencing, I-34149 Trieste, Italy

[4] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA

[5] Univ Texas Austin, Dept Mol Biosci, Austin, TX 78712 USA

[6] VisMederi Res Srl, I-53100 Siena, Italy

[7] Univ Siena, Dept Mol & Dev Med, I-53100 Siena, Italy

[8] Imperial Coll, Fac Med, London SW7 2DD, England

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2021年 / 118卷 / 36期

关键词：

SARS-CoV-2; COVID-19; emerging variants; immune evasion; antibodyresponse;

D O I：

10.1073/pnas.2103154118

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：7

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