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Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing antibodies.
Nat Med. 2021 05; 27(5):917-924.NMed

Abstract

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.

Authors+Show Affiliations

Virus & Immunity Unit, Department of Virology, Institut Pasteur, Paris, France. CNRS UMR 3569, Paris, France. Vaccine Research Institute, Créteil, France.Virus & Immunity Unit, Department of Virology, Institut Pasteur, Paris, France. CNRS UMR 3569, Paris, France. Vaccine Research Institute, Créteil, France.Virus & Immunity Unit, Department of Virology, Institut Pasteur, Paris, France. CNRS UMR 3569, Paris, France. Vaccine Research Institute, Créteil, France. Université de Paris, Sorbonne Paris Cité, Paris, France.Virus & Immunity Unit, Department of Virology, Institut Pasteur, Paris, France. CNRS UMR 3569, Paris, France. Vaccine Research Institute, Créteil, France.Virus & Immunity Unit, Department of Virology, Institut Pasteur, Paris, France. CNRS UMR 3569, Paris, France. Vaccine Research Institute, Créteil, France.Virus & Immunity Unit, Department of Virology, Institut Pasteur, Paris, France. CNRS UMR 3569, Paris, France. Vaccine Research Institute, Créteil, France.Laboratory of Humoral Immunology, Department of Immunology, Institut Pasteur, INSERM U1222, Paris, France.Virus & Immunity Unit, Department of Virology, Institut Pasteur, Paris, France. CNRS UMR 3569, Paris, France. Vaccine Research Institute, Créteil, France.Virus & Immunity Unit, Department of Virology, Institut Pasteur, Paris, France. CNRS UMR 3569, Paris, France. Vaccine Research Institute, Créteil, France. Université de Paris, Sorbonne Paris Cité, Paris, France.Virus & Immunity Unit, Department of Virology, Institut Pasteur, Paris, France. CNRS UMR 3569, Paris, France. Vaccine Research Institute, Créteil, France. Université de Paris, Sorbonne Paris Cité, Paris, France.Molecular Genetics of RNA Viruses, Department of Virology, Institut Pasteur CNRS UMR 3569, Université de Paris, Paris, France. National Reference Center for Respiratory Viruses, Institut Pasteur, Paris, France.Molecular Genetics of RNA Viruses, Department of Virology, Institut Pasteur CNRS UMR 3569, Université de Paris, Paris, France. National Reference Center for Respiratory Viruses, Institut Pasteur, Paris, France.G5 Evolutionary Genomics of RNA Viruses, Institut Pasteur, Paris, France.Molecular Genetics of RNA Viruses, Department of Virology, Institut Pasteur CNRS UMR 3569, Université de Paris, Paris, France. National Reference Center for Respiratory Viruses, Institut Pasteur, Paris, France.Molecular Genetics of RNA Viruses, Department of Virology, Institut Pasteur CNRS UMR 3569, Université de Paris, Paris, France. National Reference Center for Respiratory Viruses, Institut Pasteur, Paris, France.INSERM U1259, Université de Tours, Tours, France.CHI de Créteil, Service de Biologie Médicale, Créteil, France.CHI de Créteil, Service de Biologie Médicale, Créteil, France.CHI de Créteil, Service de Réanimation, Créteil, France.CHI de Créteil, Service des Urgences, Créteil, France.CHU de Strasbourg, Service de Pathologie Professionnelle et Médecine du Travail, Strasbourg, France.Centre d'investigation Clinique INSERM 1434, CHU Strasbourg, France. CHU de Strasbourg, Service de Neurologie, Strasbourg, France.INSERM, Functional Genomics of Solid Tumors (FunGeST), Centre de Recherche des Cordeliers, Université de Paris and Sorbonne Université, Paris, France.INSERM, Functional Genomics of Solid Tumors (FunGeST), Centre de Recherche des Cordeliers, Université de Paris and Sorbonne Université, Paris, France. Hôpital Européen Georges Pompidou, Service de Virologie, Paris, France.CHR d'Orléans, Service de maladies infectieuses, Orléans, France.G5 Evolutionary Genomics of RNA Viruses, Institut Pasteur, Paris, France.CHU de Strasbourg, Laboratoire de Virologie, Strasbourg, France. Université de Strasbourg, INSERM, IRM UMR_S 1109, Strasbourg, France.INSERM U1259, Université de Tours, Tours, France. CHRU de Tours, National Reference Center for HIV-Associated laboratory, Tours, France.Laboratory of Humoral Immunology, Department of Immunology, Institut Pasteur, INSERM U1222, Paris, France.CHR d'Orléans, Service de maladies infectieuses, Orléans, France.Molecular Genetics of RNA Viruses, Department of Virology, Institut Pasteur CNRS UMR 3569, Université de Paris, Paris, France. National Reference Center for Respiratory Viruses, Institut Pasteur, Paris, France.CHR d'Orléans, Service de maladies infectieuses, Orléans, France.Virus & Immunity Unit, Department of Virology, Institut Pasteur, Paris, France. olivier.schwartz@pasteur.fr. CNRS UMR 3569, Paris, France. olivier.schwartz@pasteur.fr. Vaccine Research Institute, Créteil, France. olivier.schwartz@pasteur.fr.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33772244

Citation

Planas, Delphine, et al. "Sensitivity of Infectious SARS-CoV-2 B.1.1.7 and B.1.351 Variants to Neutralizing Antibodies." Nature Medicine, vol. 27, no. 5, 2021, pp. 917-924.
Planas D, Bruel T, Grzelak L, et al. Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing antibodies. Nat Med. 2021;27(5):917-924.
Planas, D., Bruel, T., Grzelak, L., Guivel-Benhassine, F., Staropoli, I., Porrot, F., Planchais, C., Buchrieser, J., Rajah, M. M., Bishop, E., Albert, M., Donati, F., Prot, M., Behillil, S., Enouf, V., Maquart, M., Smati-Lafarge, M., Varon, E., Schortgen, F., ... Schwartz, O. (2021). Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing antibodies. Nature Medicine, 27(5), 917-924. https://doi.org/10.1038/s41591-021-01318-5
Planas D, et al. Sensitivity of Infectious SARS-CoV-2 B.1.1.7 and B.1.351 Variants to Neutralizing Antibodies. Nat Med. 2021;27(5):917-924. PubMed PMID: 33772244.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing antibodies. AU - Planas,Delphine, AU - Bruel,Timothée, AU - Grzelak,Ludivine, AU - Guivel-Benhassine,Florence, AU - Staropoli,Isabelle, AU - Porrot,Françoise, AU - Planchais,Cyril, AU - Buchrieser,Julian, AU - Rajah,Maaran Michael, AU - Bishop,Elodie, AU - Albert,Mélanie, AU - Donati,Flora, AU - Prot,Matthieu, AU - Behillil,Sylvie, AU - Enouf,Vincent, AU - Maquart,Marianne, AU - Smati-Lafarge,Mounira, AU - Varon,Emmanuelle, AU - Schortgen,Frédérique, AU - Yahyaoui,Layla, AU - Gonzalez,Maria, AU - De Sèze,Jérôme, AU - Péré,Hélène, AU - Veyer,David, AU - Sève,Aymeric, AU - Simon-Lorière,Etienne, AU - Fafi-Kremer,Samira, AU - Stefic,Karl, AU - Mouquet,Hugo, AU - Hocqueloux,Laurent, AU - van der Werf,Sylvie, AU - Prazuck,Thierry, AU - Schwartz,Olivier, Y1 - 2021/03/26/ PY - 2021/02/12/received PY - 2021/03/11/accepted PY - 2021/3/28/pubmed PY - 2021/5/25/medline PY - 2021/3/27/entrez SP - 917 EP - 924 JF - Nature medicine JO - Nat Med VL - 27 IS - 5 N2 - 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. SN - 1546-170X UR - https://www.unboundmedicine.com/medline/citation/33772244/Sensitivity_of_infectious_SARS_CoV_2_B_1_1_7_and_B_1_351_variants_to_neutralizing_antibodies_ L2 - https://doi.org/10.1038/s41591-021-01318-5 DB - PRIME DP - Unbound Medicine ER -