Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies

Dami A. Collier, Anna Marco, Isabella A. T. M. Ferreira, Bo Meng, Rawlings P. Datir, Alexandra C. Walls, Steven A. Kemp, Jessica Bassi, Dora Pinto, Chiara Silacci-Fregni, Siro Bianchi, M. Alejandra Tortorici, John Bowen, Katja Culap, Stefano Jaconi, Elisabetta Cameroni, Gyorgy Snell, Matteo S. Pizzuto, Alessandra Franzetti Pellanda, Christian Garzoni, Agostino Riva, Anne Elmer, Nathalie Kingston, Barbara Graves, Laura E. McCoy, Kenneth G. C. Smith, John R. Bradley, Nigel Temperton, Lourdes Ceron-Gutierrez, Gabriela Barcenas-Morales, William Harvey, Herbert W. Virgin, Antonio Lanzavecchia, Luca Piccoli, Rainer Doffinger, Mark Wills, David Veesler, Davide Corti () and Ravindra K. Gupta ()
Additional contact information
Dami A. Collier: Cambridge Institute of Therapeutic Immunology & Infectious Disease
Anna Marco: Humabs Biomed SA, a subsidiary of Vir Biotechnology
Isabella A. T. M. Ferreira: Cambridge Institute of Therapeutic Immunology & Infectious Disease
Bo Meng: Cambridge Institute of Therapeutic Immunology & Infectious Disease
Rawlings P. Datir: Cambridge Institute of Therapeutic Immunology & Infectious Disease
Alexandra C. Walls: University of Washington
Steven A. Kemp: Cambridge Institute of Therapeutic Immunology & Infectious Disease
Jessica Bassi: Humabs Biomed SA, a subsidiary of Vir Biotechnology
Dora Pinto: Humabs Biomed SA, a subsidiary of Vir Biotechnology
Chiara Silacci-Fregni: Humabs Biomed SA, a subsidiary of Vir Biotechnology
Siro Bianchi: Humabs Biomed SA, a subsidiary of Vir Biotechnology
M. Alejandra Tortorici: University of Washington
John Bowen: University of Washington
Katja Culap: Humabs Biomed SA, a subsidiary of Vir Biotechnology
Stefano Jaconi: Humabs Biomed SA, a subsidiary of Vir Biotechnology
Elisabetta Cameroni: Humabs Biomed SA, a subsidiary of Vir Biotechnology
Gyorgy Snell: Vir Biotechnology
Matteo S. Pizzuto: Humabs Biomed SA, a subsidiary of Vir Biotechnology
Alessandra Franzetti Pellanda: Clinica Luganese Moncucco
Christian Garzoni: Clinica Luganese Moncucco
Agostino Riva: University of Milan
Anne Elmer: NIHR Cambridge Clinical Research Facility
Nathalie Kingston: NIHR Bioresource
Barbara Graves: NIHR Bioresource
Laura E. McCoy: University College London
Kenneth G. C. Smith: Cambridge Institute of Therapeutic Immunology & Infectious Disease
John R. Bradley: University of Cambridge
Nigel Temperton: University of Kent
Lourdes Ceron-Gutierrez: Addenbrooke’s Hospital
Gabriela Barcenas-Morales: Addenbrooke’s Hospital
William Harvey: University of Glasgow
Herbert W. Virgin: Vir Biotechnology
Antonio Lanzavecchia: Humabs Biomed SA, a subsidiary of Vir Biotechnology
Luca Piccoli: Humabs Biomed SA, a subsidiary of Vir Biotechnology
Rainer Doffinger: Addenbrooke’s Hospital
Mark Wills: University of Cambridge
David Veesler: University of Washington
Davide Corti: Humabs Biomed SA, a subsidiary of Vir Biotechnology
Ravindra K. Gupta: Cambridge Institute of Therapeutic Immunology & Infectious Disease

Nature, 2021, vol. 593, issue 7857, 136-141

Abstract: Abstract Transmission of SARS-CoV-2 is uncontrolled in many parts of the world; control is compounded in some areas by the higher transmission potential of the B.1.1.7 variant1, which has now been reported in 94 countries. It is unclear whether the response of the virus to vaccines against SARS-CoV-2 on the basis of the prototypic strain will be affected by the mutations found in B.1.1.7. Here we assess the immune responses of individuals after vaccination with the mRNA-based vaccine BNT162b22. We measured neutralizing antibody responses after the first and second immunizations using pseudoviruses that expressed the wild-type spike protein or a mutated spike protein that contained the eight amino acid changes found in the B.1.1.7 variant. The sera from individuals who received the vaccine exhibited a broad range of neutralizing titres against the wild-type pseudoviruses that were modestly reduced against the B.1.1.7 variant. This reduction was also evident in sera from some patients who had recovered from COVID-19. Decreased neutralization of the B.1.1.7 variant was also observed for monoclonal antibodies that target the N-terminal domain (9 out of 10) and the receptor-binding motif (5 out of 31), but not for monoclonal antibodies that recognize the receptor-binding domain that bind outside the receptor-binding motif. Introduction of the mutation that encodes the E484K substitution in the B.1.1.7 background to reflect a newly emerged variant of concern (VOC 202102/02) led to a more-substantial loss of neutralizing activity by vaccine-elicited antibodies and monoclonal antibodies (19 out of 31) compared with the loss of neutralizing activity conferred by the mutations in B.1.1.7 alone. The emergence of the E484K substitution in a B.1.1.7 background represents a threat to the efficacy of the BNT162b2 vaccine.

Date: 2021
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DOI: 10.1038/s41586-021-03412-7

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