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

Collier, Dami A., De Marco, Anna, Ferreira, Isabella A.T.M., Meng, Bo, Datir, Rawlings, Walls, Alexandra C., Kemp S, Steven A., Bassi, Jessica, Pinto, Dora, Fregni, Chiara Silacci, Bianchi, Siro, Tortorici, M. Alejandra, Bowen, John, Culap, Katja, Jaconi, Stefano, Cameroni, Elisabetta, Snell, Gyorgy, Pizzuto, Matteo S., Pellanda, Alessandra Franzetti, Garzoni, Christian, Riva, Agostino, Elmer, Anne, Kingston, Nathalie, Graves, Barbara, McCoy, Laura E., Smith, Kenneth G. C., Bradley, John R., Temperton, Nigel, Lourdes Ceron-Gutierrez, L., Barcenas-Morales, Gabriela, Harvey, William, Virgin, Herbert W., Lanzavecchia, Antonio, Piccoli, Luca, Doffinger, Rainer, Wills, Mark, Veesler, David, Corti, Davide, Gupta, Ravindra K., The CITIID-NIHR BioResource COVID-19 Collaboration, , The COVID-19 Genomics UK (COG-UK) consortium, , Bashton, Matthew, Young, Greg, McCann, Clare, Nelson, Andrew and Smith, Darren (2021) Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies. Nature, 593 (7857). pp. 136-141. ISSN 0028-0836

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Abstract

SARS-CoV-2 transmission is uncontrolled in many parts of the world, compounded in some areas by higher transmission potential of the B1.1.7 variant1 now reported in 94 countries. It is unclear whether responses to SARS-CoV-2 vaccines based on the prototypic strain will be impacted by mutations found in B.1.1.7. Here we assessed immune responses following vaccination with mRNA-based vaccine BNT162b22. We measured neutralising antibody responses following first and second immunisations using pseudoviruses expressing the wild-type Spike protein or the 8 amino acid mutations found in the B.1.1.7 spike protein. The vaccine sera exhibited a broad range of neutralising titres against the wild-type pseudoviruses that were modestly reduced against B.1.1.7 variant. This reduction was also evident in sera from some convalescent patients. Decreased B.1.1.7 neutralisation was also observed with monoclonal antibodies targeting the N-terminal domain (9 out of 10), the RBM (5 out of 31), but not in RBD neutralising mAbs binding outside the RBM. Introduction of the E484K mutation in a B.1.1.7 background to reflect a newly emergent Variant of Concern (VOC 202102/02) led to a more substantial loss of neutralising activity by vaccine-elicited antibodies and mAbs (19 out of 31) over that conferred by the B.1.1.7 mutations alone. E484K emergence on a B.1.1.7 background represents a threat to the vaccine BNT162b.

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