Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing antibodies

被引：519

作者：

Planas, Delphine ^{[1
,2
,3
]}

Bruel, Timothee ^{[1
,2
,3
]}

Grzelak, Ludivine ^{[1
,2
,3
,4
]}

Guivel-Benhassine, Florence ^{[1
,2
,3
]}

Staropoli, Isabelle ^{[1
,2
,3
]}

Porrot, Francoise ^{[1
,2
,3
]}

Planchais, Cyril ^{[5
]}

Buchrieser, Julian ^{[1
,2
,3
]}

Rajah, Maaran Michael ^{[1
,2
,3
,4
]}

Bishop, Elodie ^{[1
,2
,3
,4
]}

Albert, Melanie ^{[6
,7
]}

Donati, Flora ^{[6
,7
]}

Prot, Matthieu ^{[8
]}

Behillil, Sylvie ^{[6
,7
]}

Enouf, Vincent ^{[6
,7
]}

Maquart, Marianne ^{[9
]}

Smati-Lafarge, Mounira ^{[10
]}

Varon, Emmanuelle ^{[10
]}

Schortgen, Frederique ^{[11
]}

Yahyaoui, Layla ^{[12
]}

Gonzalez, Maria ^{[13
]}

De Seze, Jerome ^{[14
,15
]}

Pere, Helene ^{[16
,17
]}

Veyer, David ^{[16
,17
,18
]}

Seve, Aymeric ^{[19
]}

Simon-Loriere, Etienne ^{[8
]}

Fafi-Kremer, Samira ^{[20
,21
]}

Stefic, Karl ^{[9
,22
]}

Mouquet, Hugo ^{[5
]}

Hocqueloux, Laurent ^{[19
]}

van der Werf, Sylvie ^{[6
,7
]}

Prazuck, Thierry ^{[19
]}

Schwartz, Olivier ^{[1
,2
,3
]}

机构：

[1] Inst Pasteur, Dept Virol, Virus & Immun Unit, Paris, France

[2] CNRS UMR 3569, Paris, France

[3] Vaccine Res Inst, Creteil, France

[4] Univ Paris, Sorbonne Paris Cite, Paris, France

[5] Inst Pasteur, Dept Immunol, Lab Humoral Immunol, INSERM U1222, Paris, France

[6] Univ Paris, Inst Pasteur CNRS UMR 3569, Dept Virol, Mol Genet RNA Viruses, Paris, France

[7] Inst Pasteur, Natl Reference Ctr Resp Viruses, Paris, France

[8] Inst Pasteur, G5 Evolutionary Genom RNA Viruses, Paris, France

[9] Univ Tours, INSERM U1259, Tours, France

[10] CHI Creteil, Serv Biol Med, Creteil, France

[11] CHI Creteil, Serv Reanimat, Creteil, France

[12] CHI Creteil, Serv Urgences, Creteil, France

[13] CHU Strasbourg, Serv Pathol Profess & Med Travail, Strasbourg, France

[14] CHU Strasbourg, Ctr Invest Clin INSERM 1434, Strasbourg, France

[15] CHU Strasbourg, Serv Neurol, Strasbourg, France

[16] Univ Paris, Ctr Rech Cordeliers, INSERM, Funct Genom Solid Tumors FunGeST, Paris, France

[17] Sorbonne Univ, Paris, France

[18] Hop Europeen Georges Pompidou, Serv Virol, Paris, France

[19] CHR Orleans, Serv Malad Infect, Orleans, France

[20] CHU Strasbourg, Lab Virol, Strasbourg, France

[21] Univ Strasbourg, INSERM, IRM UMR S 1109, Strasbourg, France

[22] CHRU Tours, Natl Reference Ctr HIV Associated Lab, Tours, France

来源：

NATURE MEDICINE | 2021年 / 27卷 / 05期

关键词：

MUTATIONS;

D O I：

10.1038/s41591-021-01318-5

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Sera from convalescent individuals with coronavirus disease 2019 and from individuals vaccinated with BNT162b2 have reduced ability to neutralize SARS-CoV-2 variants B1.1.7 and B.1.351, but antibody potency against the variants increases after two vaccine doses. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.7 and B.1.351 variants were first identified in the United Kingdom and South Africa, respectively, and have since spread to many countries. These variants harboring diverse mutations in the gene encoding the spike protein raise important concerns about their immune evasion potential. Here, we isolated infectious B.1.1.7 and B.1.351 strains from acutely infected individuals. We examined sensitivity of the two variants to SARS-CoV-2 antibodies present in sera and nasal swabs from individuals infected with previously circulating strains or who were recently vaccinated, in comparison with a D614G reference virus. We utilized a new rapid neutralization assay, based on reporter cells that become positive for GFP after overnight infection. Sera from 58 convalescent individuals collected up to 9 months after symptoms, similarly neutralized B.1.1.7 and D614G. In contrast, after 9 months, convalescent sera had a mean sixfold reduction in neutralizing titers, and 40% of the samples lacked any activity against B.1.351. Sera from 19 individuals vaccinated twice with Pfizer Cominarty, longitudinally tested up to 6 weeks after vaccination, were similarly potent against B.1.1.7 but less efficacious against B.1.351, when compared to D614G. Neutralizing titers increased after the second vaccine dose, but remained 14-fold lower against B.1.351. In contrast, sera from convalescent or vaccinated individuals similarly bound the three spike proteins in a flow cytometry-based serological assay. Neutralizing antibodies were rarely detected in nasal swabs from vaccinees. Thus, faster-spreading SARS-CoV-2 variants acquired a partial resistance to neutralizing antibodies generated by natural infection or vaccination, which was most frequently detected in individuals with low antibody levels. Our results indicate that B1.351, but not B.1.1.7, may increase the risk of infection in immunized individuals.

引用

页码：917 / +

页数：16

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