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

Collier, D. A. et al. (2021) Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies. Nature, 593(7857), pp. 136-141. (doi: 10.1038/s41586-021-03412-7) (PMID:33706364)

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 variant 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 BNT162b2 . 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.

• Item Type: Articles
• Additional Information: RKG is supported by a Wellcome Trust Senior Fellowship in Clinical Science (WT108082AIA). LEM is supported by a Medical Research Council Career Development Award (MR/R008698/1). SAK is supported by the Bill and Melinda Gates Foundation via PANGEA grant: OPP1175094. DAC is supported by a Wellcome Trust Clinical PhD Research Fellowship. KGCS is the recipient of a Wellcome Investigator Award (200871/Z/16/Z). This research was supported by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, the Cambridge Clinical Trials Unit (CCTU), and the NIHR BioResource. This study was supported by the National Institute of General Medical Sciences (R01GM120553 to D.V.), the National Institute of Allergy and Infectious Diseases (DP1AI158186 and HHSN272201700059C to D.V.), a Pew Biomedical Scholars Award (D.V.), an Investigators in the Pathogenesis of Infectious Disease Awards from the Burroughs Wellcome Fund (D.V.) and Fast Grants (D.V.).
• Keywords: SARS-CoV-2, vaccines, virology.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Harvey, Dr William
• Authors: Collier, D. A., De Marco, A., Ferreira, I. A. T. M., Meng, B., Datir, R., Walls, A. C., Kemp S, S. A., Bassi, J., Pinto, D., Fregni, C. S., Bianchi, S., Tortorici, M. A., Bowen, J., Culap, K., Jaconi, S., Cameroni, E., Snell, G., Pizzuto, M. S., Pellanda, A. F., Garzoni, C., Riva, A., Elmer, A., Kingston, N., Graves, B., McCoy, L. E., Smith, K. G. C., Bradley, J. R., Temperton, N., Lourdes Ceron-Gutierrez, L., Barcenas-Morales, G., Harvey, W., Virgin, H. W., Lanzavecchia, A., Piccoli, L., Doffinger, R., Wills, M., Veesler, D., Corti, D., and Gupta, R. K.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research; College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
• Journal Name: Nature
• Publisher: Nature Research
• ISSN: 0028-0836
• ISSN (Online): 1476-4687
• Published Online: 11 March 2021
• Copyright Holders: Copyright © 2021 The Authors
• First Published: First published in Nature 593(7857): 136-141
• Publisher Policy: Reproduced in accordance with the publisher copyright policy