@article{f9928fbdf8f443d6b2bcc712d969709e,
title = "SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway",
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 (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant.",
author = "{PITCH Consortium} and {The COVID-19 Genomics UK (COG-UK) Consortium} and Willett, {Brian J.} and Joe Grove and MacLean, {Oscar A.} and Craig Wilkie and Lorenzo, {Giuditta De} and Wilhelm Furnon and Diego Cantoni and Sam Scott and Nicola Logan and Shirin Ashraf and Maria Manali and Agnieszka Szemiel and Vanessa Cowton and Elen Vink and Harvey, {William T.} and Chris Davis and Patawee Asamaphan and Katherine Smollett and Lily Tong and Richard Orton and Joseph Hughes and Poppy Holland and Vanessa Silva and Pascall, {David J.} and Kathryn Puxty and Filipe, {Ana da Silva} and Gonzalo Yebra and Sharif Shaaban and Holden, {Matthew T. G.} and Pinto, {Rute Maria} and Rory Gunson and Kate Templeton and Murcia, {Pablo R.} and Patel, {Arvind H.} and Paul Klenerman and Susanna Dunachie and Eleanor Barnes and Anthony Brown and Sandra Adele and Barbara Kronsteiner and Murray, {Sam M.} and Priyanka Abraham and Alexandra Deeks and Ansari, {M. Azim} and Silva, {Thushan de} and Lance Turtle and Shona Moore and James Austin and Marta Gallis and John Haughney and Robertson, {David L.} and Massimo Palmarini and Surajit Ray and Thomson, {Emma C.}",
note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = jul,
day = "7",
doi = "10.1038/s41564-022-01143-7",
language = "English",
volume = "7",
pages = "1161--1179",
journal = "Nature Microbiology",
issn = "2058-5276",
publisher = "Nature Research",
number = "8",
}