Abstract

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron, the fifth VOC to be described, harbours 30 amino acid mutations in spike including 15 in the receptor-binding domain. Here, we demonstrate substantial evasion of neutralisation by Omicron in vitro using sera from vaccinated individuals. Importantly, these data are mirrored by a substantial reduction in real-world vaccine effectiveness that is partially restored by booster vaccination. We also demonstrate that Omicron does not induce cell syncytia and favours a TMPRSS2-independent endosomal entry pathway. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant.

Rights

The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. http://creativecommons.org/licenses/by-nc-nd/4.0/

Cite as

Willett, B., Grove, J., MacLean, O., Wilkie, C., Logan, N., De Lorenzo, G., Furnon, W., Scott, S., Manali, M., Szemiel, A., Ashraf, S., Vink, E., Harvey, W., Davis, C., Orton, R., Hughes, J., Holland, P., Silva, V., Pascall, D., Puxty, K., Da Silva Filipe, A., Yebra, G., Shabaan, S., Holden, M., Pinto, R., Gunson, R., Templeton, K., Murcia, P., Patel, A., The COVID-19 Genomics UK (COG-UK) Consortium, Haughney, J., Robertson, D., Palmarini, M., Ray, S. & Thomson, E. 2022, 'The hyper-transmissible SARS-CoV-2 Omicron variant exhibits significant antigenic change, vaccine escape and a switch in cell entry mechanism'. To be published in MedRxiv [Preprint]. Available at: https://doi.org/10.1101/2022.01.03.21268111

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Last updated: 16 June 2022
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