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SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway
Nature Microbiology, Volume: 7, Issue: 8, Pages: 1161 - 1179
Swansea University Author: Ronan Lyons
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DOI (Published version): 10.1038/s41564-022-01143-7
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...
Published in: | Nature Microbiology |
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ISSN: | 2058-5276 |
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Springer Science and Business Media LLC
2022
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URI: | https://cronfa.swan.ac.uk/Record/cronfa66418 |
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<?xml version="1.0" encoding="utf-8"?><rfc1807 xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:xsd="http://www.w3.org/2001/XMLSchema"><bib-version>v2</bib-version><id>66418</id><entry>2024-05-14</entry><title>SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway</title><swanseaauthors><author><sid>83efcf2a9dfcf8b55586999d3d152ac6</sid><ORCID>0000-0001-5225-000X</ORCID><firstname>Ronan</firstname><surname>Lyons</surname><name>Ronan Lyons</name><active>true</active><ethesisStudent>false</ethesisStudent></author></swanseaauthors><date>2024-05-14</date><deptcode>MEDS</deptcode><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.</abstract><type>Journal Article</type><journal>Nature Microbiology</journal><volume>7</volume><journalNumber>8</journalNumber><paginationStart>1161</paginationStart><paginationEnd>1179</paginationEnd><publisher>Springer Science and Business Media LLC</publisher><placeOfPublication/><isbnPrint/><isbnElectronic/><issnPrint/><issnElectronic>2058-5276</issnElectronic><keywords/><publishedDay>1</publishedDay><publishedMonth>8</publishedMonth><publishedYear>2022</publishedYear><publishedDate>2022-08-01</publishedDate><doi>10.1038/s41564-022-01143-7</doi><url/><notes>Publisher Correction: SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway available at https://doi.org/10.1038/s41564-022-01241-6</notes><college>COLLEGE NANME</college><department>Medical School</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>MEDS</DepartmentCode><institution>Swansea University</institution><apcterm/><funders>We thank the participants of the DOVE study and T. McSorley and her nursing team at the NHS GG&C clinical research facility; A. Hamilton, L. Stirling and C. Mayor from the NHS GG&C SafeHaven team for their invaluable input in facilitating this study; P. Olmo for administrative support, and C. Robertson and A. Sheikh for statistical advice; and all the researchers who have shared genome data openly via the Global Initiative on Sharing All Influenza Data (GISAID). Funding was provided by Health Data Research UK (HDR UK) for the Evaluation of Variants Affecting Deployed COVID-19 Vaccine (EVADE) study (E.C.T., S.R., O.A.M., C.W. and B.J.W.; grant code: 2021.0155). This research is part of the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant ref MC_PC_20058). This work was also supported by The Alan Turing Institute via ‘Towards Turing 2.0’ EPSRC Grant Funding. COG-UK is supported by funding from the Medical Research Council (MRC, part of UK Research & Innovation (UKRI)), the National Institute of Health Research (NIHR; grant code: MC_PC_19027) and Genome Research Limited, operating as the Wellcome Sanger Institute (R.M.P., D.L.R. and E.C.T.). Medical Research Council (MRC) provided funding for both the COVID-19 DeplOyed VaccinE (DOVE) study (grant code: MCUU1201412) and COG-UK (E.C.T.). A.d.S.F., J.H., R.O., J.G., E.C.T., N.L. and D.L.R. were funded by the Medical Research Council (MRC; grant code: MC_UU_12014/12). W.T.H. was supported by the MRC (grant codes MR/R024758/1 and MR/W005611/1). The G2P-UK National Virology Consortium was funded by UK Research and Innovation (UKRI) award MR/W005611/1 (M.P., E.C.T., A.H.P. and D.L.R.). D.L.R. was funded by Wellcome Trust (grant code: 220977/Z/20/Z). N.L. and B.J.W. were funded by the Biotechnology and Biological Sciences Research Council (grant codes: BBSRC, BB/R004250/1 and BB/R019843/1). J.G. was funded by a Wellcome Trust and Royal Society Sir Henry Dale Fellowship (grant code: 107653/Z/15/A). D.J.P. was funded by UKRI through the JUNIPER consortium (grant number MR/V038613/1). The PITCH Consortium is funded by the United Kingdom Department of Health and Social Care.</funders><projectreference/><lastEdited>2024-06-24T12:09:41.3388831</lastEdited><Created>2024-05-14T15:36:46.9182002</Created><path><level id="1">Faculty of Medicine, Health and Life Sciences</level><level id="2">Swansea University Medical School - Health Data Science</level></path><authors><author><firstname>Brian J.</firstname><surname>Willett</surname><orcid>0000-0001-8912-3266</orcid><order>1</order></author><author><firstname>Joe</firstname><surname>Grove</surname><orcid>0000-0001-5390-7579</orcid><order>2</order></author><author><firstname>Oscar A.</firstname><surname>MacLean</surname><order>3</order></author><author><firstname>Craig</firstname><surname>Wilkie</surname><orcid>0000-0003-0805-0195</orcid><order>4</order></author><author><firstname>Giuditta De</firstname><surname>Lorenzo</surname><orcid>0000-0002-2736-8740</orcid><order>5</order></author><author><firstname>Wilhelm</firstname><surname>Furnon</surname><orcid>0000-0002-5588-4232</orcid><order>6</order></author><author><firstname>Diego</firstname><surname>Cantoni</surname><order>7</order></author><author><firstname>Sam</firstname><surname>Scott</surname><orcid>0000-0001-7080-8038</orcid><order>8</order></author><author><firstname>Nicola</firstname><surname>Logan</surname><order>9</order></author><author><firstname>Shirin</firstname><surname>Ashraf</surname><orcid>0000-0002-6468-0258</orcid><order>10</order></author><author><firstname>Maria</firstname><surname>Manali</surname><order>11</order></author><author><firstname>Agnieszka</firstname><surname>Szemiel</surname><order>12</order></author><author><firstname>Vanessa</firstname><surname>Cowton</surname><orcid>0000-0003-1813-7825</orcid><order>13</order></author><author><firstname>Elen</firstname><surname>Vink</surname><orcid>0000-0001-8535-6214</orcid><order>14</order></author><author><firstname>William T.</firstname><surname>Harvey</surname><order>15</order></author><author><firstname>Chris</firstname><surname>Davis</surname><order>16</order></author><author><firstname>Patawee</firstname><surname>Asamaphan</surname><order>17</order></author><author><firstname>Katherine</firstname><surname>Smollett</surname><order>18</order></author><author><firstname>Lily</firstname><surname>Tong</surname><orcid>0000-0003-3882-3339</orcid><order>19</order></author><author><firstname>Richard</firstname><surname>Orton</surname><order>20</order></author><author><firstname>Joseph</firstname><surname>Hughes</surname><orcid>0000-0003-2556-2563</orcid><order>21</order></author><author><firstname>Poppy</firstname><surname>Holland</surname><orcid>0000-0001-9708-9555</orcid><order>22</order></author><author><firstname>Vanessa</firstname><surname>Silva</surname><order>23</order></author><author><firstname>David J.</firstname><surname>Pascall</surname><orcid>0000-0002-7543-0860</orcid><order>24</order></author><author><firstname>Kathryn</firstname><surname>Puxty</surname><orcid>0000-0002-5742-6171</orcid><order>25</order></author><author><firstname>Ana da Silva</firstname><surname>Filipe</surname><orcid>0000-0002-9442-2903</orcid><order>26</order></author><author><firstname>Gonzalo</firstname><surname>Yebra</surname><orcid>0000-0002-3472-3667</orcid><order>27</order></author><author><firstname>Sharif</firstname><surname>Shaaban</surname><order>28</order></author><author><firstname>Matthew T. 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P.</firstname><surname>Kidd</surname><order>212</order></author><author><firstname>Lisa J.</firstname><surname>Levett</surname><order>213</order></author><author><firstname>Monika</firstname><surname>Pusok</surname><order>214</order></author><author><firstname>Paul R.</firstname><surname>Grant</surname><order>215</order></author><author><firstname>Stuart</firstname><surname>Kirk</surname><order>216</order></author><author><firstname>Wendy</firstname><surname>Chatterton</surname><order>217</order></author><author><firstname>Li</firstname><surname>Xu-McCrae</surname><order>218</order></author><author><firstname>Darren L.</firstname><surname>Smith</surname><order>219</order></author><author><firstname>Gregory R.</firstname><surname>Young</surname><order>220</order></author><author><firstname>Matthew</firstname><surname>Bashton</surname><order>221</order></author><author><firstname>Katie</firstname><surname>Kitchman</surname><order>222</order></author><author><firstname>Kavitha</firstname><surname>Gajee</surname><order>223</order></author><author><firstname>Kirstine</firstname><surname>Eastick</surname><order>224</order></author><author><firstname>Patrick J.</firstname><surname>Lillie</surname><order>225</order></author><author><firstname>Phillipa J.</firstname><surname>Burns</surname><order>226</order></author><author><firstname>William</firstname><surname>Everson</surname><order>227</order></author><author><firstname>Alison</firstname><surname>Cox</surname><order>228</order></author><author><firstname>Alison H.</firstname><surname>Holmes</surname><order>229</order></author><author><firstname>Frances</firstname><surname>Bolt</surname><order>230</order></author><author><firstname>James R.</firstname><surname>Price</surname><order>231</order></author><author><firstname>Marcus</firstname><surname>Pond</surname><order>232</order></author><author><firstname>Paul A.</firstname><surname>Randell</surname><order>233</order></author><author><firstname>Pinglawathee</firstname><surname>Madona</surname><order>234</order></author><author><firstname>Siddharth</firstname><surname>Mookerjee</surname><order>235</order></author><author><firstname>Erik M.</firstname><surname>Volz</surname><order>236</order></author><author><firstname>Lily</firstname><surname>Geidelberg</surname><order>237</order></author><author><firstname>Manon</firstname><surname>Ragonnet-Cronin</surname><order>238</order></author><author><firstname>Olivia</firstname><surname>Boyd</surname><order>239</order></author><author><firstname>Rob</firstname><surname>Johnson</surname><order>240</order></author><author><firstname>Cassie F.</firstname><surname>Pope</surname><order>241</order></author><author><firstname>Adam A.</firstname><surname>Witney</surname><order>242</order></author><author><firstname>Irene M.</firstname><surname>Monahan</surname><order>243</order></author><author><firstname>Kenneth G.</firstname><surname>Laing</surname><order>244</order></author><author><firstname>Katherine L.</firstname><surname>Smollett</surname><order>245</order></author><author><firstname>Alan</firstname><surname>McNally</surname><order>246</order></author><author><firstname>Claire</firstname><surname>McMurray</surname><order>247</order></author><author><firstname>Joanne</firstname><surname>Stockton</surname><order>248</order></author><author><firstname>Joshua</firstname><surname>Quick</surname><order>249</order></author><author><firstname>Nicholas J.</firstname><surname>Loman</surname><order>250</order></author><author><firstname>Radoslaw</firstname><surname>Poplawski</surname><order>251</order></author><author><firstname>Sam</firstname><surname>Nicholls</surname><order>252</order></author><author><firstname>Will</firstname><surname>Rowe</surname><order>253</order></author><author><firstname>Anibolina</firstname><surname>Castigador</surname><order>254</order></author><author><firstname>Emily</firstname><surname>Macnaughton</surname><order>255</order></author><author><firstname>Kate El</firstname><surname>Bouzidi</surname><order>256</order></author><author><firstname>Malur</firstname><surname>Sudhanva</surname><order>257</order></author><author><firstname>Temi</firstname><surname>Lampejo</surname><order>258</order></author><author><firstname>Rocio T. Martinez</firstname><surname>Nunez</surname><order>259</order></author><author><firstname>Cassie</firstname><surname>Breen</surname><order>260</order></author><author><firstname>Graciela</firstname><surname>Sluga</surname><order>261</order></author><author><firstname>Karen T.</firstname><surname>Withell</surname><order>262</order></author><author><firstname>Nicholas W.</firstname><surname>Machin</surname><order>263</order></author><author><firstname>Ryan P.</firstname><surname>George</surname><order>264</order></author><author><firstname>Shazaad S. 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de</firstname><surname>Angelis</surname><order>273</order></author><author><firstname>David</firstname><surname>Pascall</surname><order>274</order></author><author><firstname>Afrida</firstname><surname>Mukaddas</surname><order>275</order></author><author><firstname>Alice</firstname><surname>Broos</surname><order>276</order></author><author><firstname>Ana da Silva</firstname><surname>Filipe</surname><order>277</order></author><author><firstname>Daniel</firstname><surname>Mair</surname><order>278</order></author><author><firstname>David L.</firstname><surname>Robertson</surname><order>279</order></author><author><firstname>Derek W.</firstname><surname>Wright</surname><order>280</order></author><author><firstname>Emma C.</firstname><surname>Thomson</surname><order>281</order></author><author><firstname>Igor</firstname><surname>Starinskij</surname><order>282</order></author><author><firstname>Ioulia</firstname><surname>Tsatsani</surname><order>283</order></author><author><firstname>James G.</firstname><surname>Shepherd</surname><order>284</order></author><author><firstname>Jenna</firstname><surname>Nichols</surname><order>285</order></author><author><firstname>Joseph</firstname><surname>Hughes</surname><order>286</order></author><author><firstname>Kyriaki</firstname><surname>Nomikou</surname><order>287</order></author><author><firstname>Lily</firstname><surname>Tong</surname><order>288</order></author><author><firstname>Richard J.</firstname><surname>Orton</surname><order>289</order></author><author><firstname>Sreenu</firstname><surname>Vattipally</surname><order>290</order></author><author><firstname>William T.</firstname><surname>Harvey</surname><order>291</order></author><author><firstname>Roy</firstname><surname>Sanderson</surname><order>292</order></author><author><firstname>Sarah</firstname><surname>O’Brien</surname><order>293</order></author><author><firstname>Steven</firstname><surname>Rushton</surname><order>294</order></author><author><firstname>Jon</firstname><surname>Perkins</surname><order>295</order></author><author><firstname>Rachel</firstname><surname>Blacow</surname><order>296</order></author><author><firstname>Rory N.</firstname><surname>Gunson</surname><order>297</order></author><author><firstname>Abbie</firstname><surname>Gallagher</surname><order>298</order></author><author><firstname>Elizabeth</firstname><surname>Wastnedge</surname><order>299</order></author><author><firstname>Kate E.</firstname><surname>Templeton</surname><order>300</order></author><author><firstname>Martin P.</firstname><surname>McHugh</surname><order>301</order></author><author><firstname>Rebecca</firstname><surname>Dewar</surname><order>302</order></author><author><firstname>Seb</firstname><surname>Cotton</surname><order>303</order></author><author><firstname>Lindsay</firstname><surname>Coupland</surname><order>304</order></author><author><firstname>Rachael</firstname><surname>Stanley</surname><order>305</order></author><author><firstname>Samir</firstname><surname>Dervisevic</surname><order>306</order></author><author><firstname>Lewis G.</firstname><surname>Spurgin</surname><order>307</order></author><author><firstname>Louise</firstname><surname>Smith</surname><order>308</order></author><author><firstname>Clive</firstname><surname>Graham</surname><order>309</order></author><author><firstname>Debra</firstname><surname>Padgett</surname><order>310</order></author><author><firstname>Edward</firstname><surname>Barton</surname><order>311</order></author><author><firstname>Garren</firstname><surname>Scott</surname><order>312</order></author><author><firstname>Aidan</firstname><surname>Cross</surname><order>313</order></author><author><firstname>Mariyam</firstname><surname>Mirfenderesky</surname><order>314</order></author><author><firstname>Emma</firstname><surname>Swindells</surname><order>315</order></author><author><firstname>Jane</firstname><surname>Greenaway</surname><order>316</order></author><author><firstname>Rebecca</firstname><surname>Denton-Smith</surname><order>317</order></author><author><firstname>Robyn</firstname><surname>Turnbull</surname><order>318</order></author><author><firstname>Giles</firstname><surname>Idle</surname><order>319</order></author><author><firstname>Kevin</firstname><surname>Cole</surname><order>320</order></author><author><firstname>Amy</firstname><surname>Hollis</surname><order>321</order></author><author><firstname>Andrew</firstname><surname>Nelson</surname><order>322</order></author><author><firstname>Clare M.</firstname><surname>McCann</surname><order>323</order></author><author><firstname>John H.</firstname><surname>Henderson</surname><order>324</order></author><author><firstname>Matthew R.</firstname><surname>Crown</surname><order>325</order></author><author><firstname>Wen C.</firstname><surname>Yew</surname><order>326</order></author><author><firstname>William</firstname><surname>Stanley</surname><order>327</order></author><author><firstname>Nichola</firstname><surname>Duckworth</surname><order>328</order></author><author><firstname>Phillip</firstname><surname>Clarke</surname><order>329</order></author><author><firstname>Sarah</firstname><surname>Walsh</surname><order>330</order></author><author><firstname>Tim J.</firstname><surname>Sloan</surname><order>331</order></author><author><firstname>Kelly</firstname><surname>Bicknell</surname><order>332</order></author><author><firstname>Robert</firstname><surname>Impey</surname><order>333</order></author><author><firstname>Sarah</firstname><surname>Wyllie</surname><order>334</order></author><author><firstname>Scott</firstname><surname>Elliott</surname><order>335</order></author><author><firstname>Sharon</firstname><surname>Glaysher</surname><order>336</order></author><author><firstname>Declan T.</firstname><surname>Bradley</surname><order>337</order></author><author><firstname>Nicholas F.</firstname><surname>Killough</surname><order>338</order></author><author><firstname>Tim</firstname><surname>Wyatt</surname><order>339</order></author><author><firstname>Andrew</firstname><surname>Bosworth</surname><order>340</order></author><author><firstname>Barry B.</firstname><surname>Vipond</surname><order>341</order></author><author><firstname>Clare</firstname><surname>Pearson</surname><order>342</order></author><author><firstname>Elias</firstname><surname>Allara</surname><order>343</order></author><author><firstname>Esther</firstname><surname>Robinson</surname><order>344</order></author><author><firstname>Hannah M.</firstname><surname>Pymont</surname><order>345</order></author><author><firstname>Husam</firstname><surname>Osman</surname><order>346</order></author><author><firstname>Peter</firstname><surname>Muir</surname><order>347</order></author><author><firstname>Richard</firstname><surname>Hopes</surname><order>348</order></author><author><firstname>Stephanie</firstname><surname>Hutchings</surname><order>349</order></author><author><firstname>Martin D.</firstname><surname>Curran</surname><order>350</order></author><author><firstname>Surendra</firstname><surname>Parmar</surname><order>351</order></author><author><firstname>Alicia</firstname><surname>Thornton</surname><order>352</order></author><author><firstname>Angie</firstname><surname>Lackenby</surname><order>353</order></author><author><firstname>Chloe</firstname><surname>Bishop</surname><order>354</order></author><author><firstname>David</firstname><surname>Bibby</surname><order>355</order></author><author><firstname>David</firstname><surname>Lee</surname><order>356</order></author><author><firstname>Eileen</firstname><surname>Gallagher</surname><order>357</order></author><author><firstname>Gavin</firstname><surname>Dabrera</surname><order>358</order></author><author><firstname>Ian</firstname><surname>Harrison</surname><order>359</order></author><author><firstname>Jonathan</firstname><surname>Hubb</surname><order>360</order></author><author><firstname>Katherine A.</firstname><surname>Twohig</surname><order>361</order></author><author><firstname>Meera</firstname><surname>Chand</surname><order>362</order></author><author><firstname>Nicholas</firstname><surname>Ellaby</surname><order>363</order></author><author><firstname>Nikos</firstname><surname>Manesis</surname><order>364</order></author><author><firstname>Richard</firstname><surname>Myers</surname><order>365</order></author><author><firstname>Steven</firstname><surname>Platt</surname><order>366</order></author><author><firstname>Tamyo</firstname><surname>Mbisa</surname><order>367</order></author><author><firstname>Vicki</firstname><surname>Chalker</surname><order>368</order></author><author><firstname>Gonzalo</firstname><surname>Yebra</surname><order>369</order></author><author><firstname>Matthew T. G.</firstname><surname>Holden</surname><order>370</order></author><author><firstname>Sharif</firstname><surname>Shaaban</surname><order>371</order></author><author><firstname>Stefan</firstname><surname>Rooke</surname><order>372</order></author><author><firstname>Alec</firstname><surname>Birchley</surname><order>373</order></author><author><firstname>Alexander</firstname><surname>Adams</surname><order>374</order></author><author><firstname>Alisha</firstname><surname>Davies</surname><order>375</order></author><author><firstname>Amy</firstname><surname>Gaskin</surname><order>376</order></author><author><firstname>Bree</firstname><surname>Gatica-Wilcox</surname><order>377</order></author><author><firstname>Caoimhe</firstname><surname>McKerr</surname><order>378</order></author><author><firstname>Catherine</firstname><surname>Moore</surname><order>379</order></author><author><firstname>Catryn</firstname><surname>Williams</surname><order>380</order></author><author><firstname>Chris</firstname><surname>Williams</surname><order>381</order></author><author><firstname>David</firstname><surname>Heyburn</surname><order>382</order></author><author><firstname>Elen De</firstname><surname>Lacy</surname><order>383</order></author><author><firstname>Ember</firstname><surname>Hilvers</surname><order>384</order></author><author><firstname>Fatima</firstname><surname>Downing</surname><order>385</order></author><author><firstname>Georgia</firstname><surname>Pugh</surname><order>386</order></author><author><firstname>Hannah</firstname><surname>Jones</surname><order>387</order></author><author><firstname>Hibo</firstname><surname>Asad</surname><order>388</order></author><author><firstname>Jason</firstname><surname>Coombes</surname><order>389</order></author><author><firstname>Jessica</firstname><surname>Hey</surname><order>390</order></author><author><firstname>Jessica</firstname><surname>Powell</surname><order>391</order></author><author><firstname>Joanne</firstname><surname>Watkins</surname><order>392</order></author><author><firstname>Johnathan M.</firstname><surname>Evans</surname><order>393</order></author><author><firstname>Laia</firstname><surname>Fina</surname><order>394</order></author><author><firstname>Laura</firstname><surname>Gifford</surname><order>395</order></author><author><firstname>Lauren</firstname><surname>Gilbert</surname><order>396</order></author><author><firstname>Lee</firstname><surname>Graham</surname><order>397</order></author><author><firstname>Malorie</firstname><surname>Perry</surname><order>398</order></author><author><firstname>Mari</firstname><surname>Morgan</surname><order>399</order></author><author><firstname>Matthew</firstname><surname>Bull</surname><order>400</order></author><author><firstname>Nicole</firstname><surname>Pacchiarini</surname><order>401</order></author><author><firstname>Noel</firstname><surname>Craine</surname><order>402</order></author><author><firstname>Sally</firstname><surname>Corden</surname><order>403</order></author><author><firstname>Sara</firstname><surname>Kumziene-Summerhayes</surname><order>404</order></author><author><firstname>Sara</firstname><surname>Rey</surname><order>405</order></author><author><firstname>Sarah</firstname><surname>Taylor</surname><order>406</order></author><author><firstname>Simon</firstname><surname>Cottrell</surname><order>407</order></author><author><firstname>Sophie</firstname><surname>Jones</surname><order>408</order></author><author><firstname>Sue</firstname><surname>Edwards</surname><order>409</order></author><author><firstname>Tara</firstname><surname>Annett</surname><order>410</order></author><author><firstname>Alexander J.</firstname><surname>Trotter</surname><order>411</order></author><author><firstname>Alison E.</firstname><surname>Mather</surname><order>412</order></author><author><firstname>Alp</firstname><surname>Aydin</surname><order>413</order></author><author><firstname>Andrew J.</firstname><surname>Page</surname><order>414</order></author><author><firstname>David J.</firstname><surname>Baker</surname><order>415</order></author><author><firstname>Ebenezer</firstname><surname>Foster-Nyarko</surname><order>416</order></author><author><firstname>Gemma L.</firstname><surname>Kay</surname><order>417</order></author><author><firstname>Justin</firstname><surname>O’Grady</surname><order>418</order></author><author><firstname>Leonardo de Oliveira</firstname><surname>Martins</surname><order>419</order></author><author><firstname>Lizzie</firstname><surname>Meadows</surname><order>420</order></author><author><firstname>Nabil-Fareed</firstname><surname>Alikhan</surname><order>421</order></author><author><firstname>Sophie J.</firstname><surname>Prosolek</surname><order>422</order></author><author><firstname>Steven</firstname><surname>Rudder</surname><order>423</order></author><author><firstname>Thanh</firstname><surname>Le-Viet</surname><order>424</order></author><author><firstname>Anna</firstname><surname>Casey</surname><order>425</order></author><author><firstname>Liz</firstname><surname>Ratcliffe</surname><order>426</order></author><author><firstname>Aditi</firstname><surname>Singh</surname><order>427</order></author><author><firstname>Arun</firstname><surname>Mariappan</surname><order>428</order></author><author><firstname>Chris</firstname><surname>Baxter</surname><order>429</order></author><author><firstname>Clara</firstname><surname>Radulescu</surname><order>430</order></author><author><firstname>David 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v2 66418 2024-05-14 SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway 83efcf2a9dfcf8b55586999d3d152ac6 0000-0001-5225-000X Ronan Lyons Ronan Lyons true false 2024-05-14 MEDS 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. Journal Article Nature Microbiology 7 8 1161 1179 Springer Science and Business Media LLC 2058-5276 1 8 2022 2022-08-01 10.1038/s41564-022-01143-7 Publisher Correction: SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway available at https://doi.org/10.1038/s41564-022-01241-6 COLLEGE NANME Medical School COLLEGE CODE MEDS Swansea University We thank the participants of the DOVE study and T. McSorley and her nursing team at the NHS GG&C clinical research facility; A. Hamilton, L. Stirling and C. Mayor from the NHS GG&C SafeHaven team for their invaluable input in facilitating this study; P. Olmo for administrative support, and C. Robertson and A. Sheikh for statistical advice; and all the researchers who have shared genome data openly via the Global Initiative on Sharing All Influenza Data (GISAID). Funding was provided by Health Data Research UK (HDR UK) for the Evaluation of Variants Affecting Deployed COVID-19 Vaccine (EVADE) study (E.C.T., S.R., O.A.M., C.W. and B.J.W.; grant code: 2021.0155). This research is part of the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant ref MC_PC_20058). This work was also supported by The Alan Turing Institute via ‘Towards Turing 2.0’ EPSRC Grant Funding. COG-UK is supported by funding from the Medical Research Council (MRC, part of UK Research & Innovation (UKRI)), the National Institute of Health Research (NIHR; grant code: MC_PC_19027) and Genome Research Limited, operating as the Wellcome Sanger Institute (R.M.P., D.L.R. and E.C.T.). Medical Research Council (MRC) provided funding for both the COVID-19 DeplOyed VaccinE (DOVE) study (grant code: MCUU1201412) and COG-UK (E.C.T.). A.d.S.F., J.H., R.O., J.G., E.C.T., N.L. and D.L.R. were funded by the Medical Research Council (MRC; grant code: MC_UU_12014/12). W.T.H. was supported by the MRC (grant codes MR/R024758/1 and MR/W005611/1). The G2P-UK National Virology Consortium was funded by UK Research and Innovation (UKRI) award MR/W005611/1 (M.P., E.C.T., A.H.P. and D.L.R.). D.L.R. was funded by Wellcome Trust (grant code: 220977/Z/20/Z). N.L. and B.J.W. were funded by the Biotechnology and Biological Sciences Research Council (grant codes: BBSRC, BB/R004250/1 and BB/R019843/1). J.G. was funded by a Wellcome Trust and Royal Society Sir Henry Dale Fellowship (grant code: 107653/Z/15/A). D.J.P. was funded by UKRI through the JUNIPER consortium (grant number MR/V038613/1). The PITCH Consortium is funded by the United Kingdom Department of Health and Social Care. 2024-06-24T12:09:41.3388831 2024-05-14T15:36:46.9182002 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Health Data Science Brian J. Willett 0000-0001-8912-3266 1 Joe Grove 0000-0001-5390-7579 2 Oscar A. MacLean 3 Craig Wilkie 0000-0003-0805-0195 4 Giuditta De Lorenzo 0000-0002-2736-8740 5 Wilhelm Furnon 0000-0002-5588-4232 6 Diego Cantoni 7 Sam Scott 0000-0001-7080-8038 8 Nicola Logan 9 Shirin Ashraf 0000-0002-6468-0258 10 Maria Manali 11 Agnieszka Szemiel 12 Vanessa Cowton 0000-0003-1813-7825 13 Elen Vink 0000-0001-8535-6214 14 William T. Harvey 15 Chris Davis 16 Patawee Asamaphan 17 Katherine Smollett 18 Lily Tong 0000-0003-3882-3339 19 Richard Orton 20 Joseph Hughes 0000-0003-2556-2563 21 Poppy Holland 0000-0001-9708-9555 22 Vanessa Silva 23 David J. Pascall 0000-0002-7543-0860 24 Kathryn Puxty 0000-0002-5742-6171 25 Ana da Silva Filipe 0000-0002-9442-2903 26 Gonzalo Yebra 0000-0002-3472-3667 27 Sharif Shaaban 28 Matthew T. G. Holden 29 Rute Maria Pinto 30 Rory Gunson 31 Kate Templeton 32 Pablo R. Murcia 0000-0002-4352-394x 33 Arvind H. Patel 0000-0003-4600-2047 34 Paul Klenerman 35 Susanna Dunachie 0000-0001-5665-6293 36 Susanna Dunachie 37 Paul Klenerman 38 Eleanor Barnes 39 Anthony Brown 40 Sandra Adele 41 Barbara Kronsteiner 42 Sam M. Murray 43 Priyanka Abraham 44 Alexandra Deeks 45 M. Azim Ansari 46 Thushan de Silva 47 Lance Turtle 48 Shona Moore 49 James Austin 50 Alex Richter 51 Christopher Duncan 52 Rebecca Payne 53 Amy Ash 54 Cherian Koshy 55 Beatrix Kele 56 Teresa Cutino-Moguel 57 Derek J. Fairley 58 James P. McKenna 59 Tanya Curran 60 Helen Adams 61 Christophe Fraser 62 David Bonsall 63 Helen Fryer 64 Katrina Lythgoe 65 Laura Thomson 66 Tanya Golubchik 67 Abigail Murray 68 Dawn Singleton 69 Shaun M. Beckwith 70 Anna Mantzouratou 71 Magdalena Barrow 72 Sarah L. Buchan 73 Nicola Reynolds 74 Ben Warne 75 Joshua Maksimovic 76 Karla Spellman 77 Kathryn McCluggage 78 Michaela John 79 Robert Beer 80 Safiah Afifi 81 Sian Morgan 82 Andrew Mack 83 Angela Marchbank 84 Anna Price 85 Arthur Morriss 86 Catherine Bresner 87 Christine Kitchen 88 Ian Merrick 89 Joel Southgate 90 Martyn Guest 91 Owen Jones 92 Robert Munn 93 Thomas R. Connor 94 Thomas Whalley 95 Trudy Workman 96 William Fuller 97 Amita Patel 98 Bindi Patel 99 Gaia Nebbia 100 Jonathan Edgeworth 101 Luke B. Snell 102 Rahul Batra 103 Themoula Charalampous 104 Angela H. Beckett 105 Ekaterina Shelest 106 Samuel C. Robson 107 Anthony P. Underwood 108 Ben E. W. Taylor 109 Corin A. Yeats 110 David M. Aanensen 111 Khalil Abudahab 112 Mirko Menegazzo 113 Amelia Joseph 114 Gemma Clark 115 Hannah C. Howson-Wells 116 Louise Berry 117 Manjinder Khakh 118 Michelle M. Lister 119 Tim Boswell 120 Vicki M. Fleming 121 Christopher W. Holmes 122 Claire L. McMurray 123 Jessica Shaw 124 Julian W. Tang 125 Karlie Fallon 126 Mina Odedra 127 Nicholas J. Willford 128 Paul W. Bird 129 Thomas Helmer 130 Lesley-Anne Williams 131 Nicola Sheriff 132 Sharon Campbell 133 Veena Raviprakash 134 Victoria Blakey 135 Christopher Moore 136 Fei Sang 137 Johnny Debebe 138 Matthew Carlile 139 Matthew W. Loose 140 Nadine Holmes 141 Victoria Wright 142 M. Estee Torok 143 William L. Hamilton 144 Alessandro M. Carabelli 145 Andrew Jermy 146 Beth Blane 147 Carol M. Churcher 148 Catherine Ludden 149 Dinesh Aggarwal 150 Elaine Westwick 151 Ellena Brooks 152 Georgina M. McManus 153 Katerina Galai 154 Ken Smith 155 Kim S. Smith 156 MacGregor Cox 157 Mireille Fragakis 158 Patrick Maxwell 159 Sarah Judges 160 Sharon J. Peacock 161 Theresa Feltwell 162 Anita Kenyon 163 Sahar Eldirdiri 164 Thomas Davis 165 Joshua F. Taylor 166 Ngee Keong Tan 167 Alex E. Zarebski 168 Bernardo Gutierrez 169 Jayna Raghwani 170 Louis du Plessis 171 Moritz U. G. Kraemer 172 Oliver G. Pybus 173 Sarah Francois 174 Stephen W. Attwood 175 Tetyana I. Vasylyeva 176 Aminu S. Jahun 177 Ian G. Goodfellow 178 Iliana Georgana 179 Malte L. Pinckert 180 Myra Hosmillo 181 Rhys Izuagbe 182 Yasmin Chaudhry 183 Felicity Ryan 184 Hannah Lowe 185 Samuel Moses 186 Luke Bedford 187 James S. Cargill 188 Warwick Hughes 189 Jonathan Moore 190 Susanne Stonehouse 191 Divya Shah 192 Jack C. D. Lee 193 Julianne R. Brown 194 Kathryn A. Harris 195 Laura Atkinson 196 Nathaniel Storey 197 Moira J. Spyer 198 Flavia Flaviani 199 Adela Alcolea-Medina 200 Jasveen Sehmi 201 John Ramble 202 Natasha Ohemeng-Kumi 203 Perminder Smith 204 Beatrice Bertolusso 205 Claire Thomas 206 Gabrielle Vernet 207 Jessica Lynch 208 Nathan Moore 209 Nicholas Cortes 210 Rebecca Williams 211 Stephen P. Kidd 212 Lisa J. Levett 213 Monika Pusok 214 Paul R. Grant 215 Stuart Kirk 216 Wendy Chatterton 217 Li Xu-McCrae 218 Darren L. Smith 219 Gregory R. Young 220 Matthew Bashton 221 Katie Kitchman 222 Kavitha Gajee 223 Kirstine Eastick 224 Patrick J. Lillie 225 Phillipa J. Burns 226 William Everson 227 Alison Cox 228 Alison H. Holmes 229 Frances Bolt 230 James R. Price 231 Marcus Pond 232 Paul A. Randell 233 Pinglawathee Madona 234 Siddharth Mookerjee 235 Erik M. Volz 236 Lily Geidelberg 237 Manon Ragonnet-Cronin 238 Olivia Boyd 239 Rob Johnson 240 Cassie F. Pope 241 Adam A. Witney 242 Irene M. Monahan 243 Kenneth G. Laing 244 Katherine L. Smollett 245 Alan McNally 246 Claire McMurray 247 Joanne Stockton 248 Joshua Quick 249 Nicholas J. Loman 250 Radoslaw Poplawski 251 Sam Nicholls 252 Will Rowe 253 Anibolina Castigador 254 Emily Macnaughton 255 Kate El Bouzidi 256 Malur Sudhanva 257 Temi Lampejo 258 Rocio T. Martinez Nunez 259 Cassie Breen 260 Graciela Sluga 261 Karen T. Withell 262 Nicholas W. Machin 263 Ryan P. George 264 Shazaad S. Y. Ahmad 265 David T. Pritchard 266 Debbie Binns 267 Nick Wong 268 Victoria James 269 Cheryl Williams 270 Chris J. Illingworth 271 Chris Jackson 272 Daniela de Angelis 273 David Pascall 274 Afrida Mukaddas 275 Alice Broos 276 Ana da Silva Filipe 277 Daniel Mair 278 David L. Robertson 279 Derek W. Wright 280 Emma C. Thomson 281 Igor Starinskij 282 Ioulia Tsatsani 283 James G. Shepherd 284 Jenna Nichols 285 Joseph Hughes 286 Kyriaki Nomikou 287 Lily Tong 288 Richard J. Orton 289 Sreenu Vattipally 290 William T. Harvey 291 Roy Sanderson 292 Sarah O’Brien 293 Steven Rushton 294 Jon Perkins 295 Rachel Blacow 296 Rory N. Gunson 297 Abbie Gallagher 298 Elizabeth Wastnedge 299 Kate E. Templeton 300 Martin P. McHugh 301 Rebecca Dewar 302 Seb Cotton 303 Lindsay Coupland 304 Rachael Stanley 305 Samir Dervisevic 306 Lewis G. Spurgin 307 Louise Smith 308 Clive Graham 309 Debra Padgett 310 Edward Barton 311 Garren Scott 312 Aidan Cross 313 Mariyam Mirfenderesky 314 Emma Swindells 315 Jane Greenaway 316 Rebecca Denton-Smith 317 Robyn Turnbull 318 Giles Idle 319 Kevin Cole 320 Amy Hollis 321 Andrew Nelson 322 Clare M. McCann 323 John H. Henderson 324 Matthew R. Crown 325 Wen C. Yew 326 William Stanley 327 Nichola Duckworth 328 Phillip Clarke 329 Sarah Walsh 330 Tim J. Sloan 331 Kelly Bicknell 332 Robert Impey 333 Sarah Wyllie 334 Scott Elliott 335 Sharon Glaysher 336 Declan T. Bradley 337 Nicholas F. Killough 338 Tim Wyatt 339 Andrew Bosworth 340 Barry B. Vipond 341 Clare Pearson 342 Elias Allara 343 Esther Robinson 344 Hannah M. Pymont 345 Husam Osman 346 Peter Muir 347 Richard Hopes 348 Stephanie Hutchings 349 Martin D. Curran 350 Surendra Parmar 351 Alicia Thornton 352 Angie Lackenby 353 Chloe Bishop 354 David Bibby 355 David Lee 356 Eileen Gallagher 357 Gavin Dabrera 358 Ian Harrison 359 Jonathan Hubb 360 Katherine A. Twohig 361 Meera Chand 362 Nicholas Ellaby 363 Nikos Manesis 364 Richard Myers 365 Steven Platt 366 Tamyo Mbisa 367 Vicki Chalker 368 Gonzalo Yebra 369 Matthew T. G. Holden 370 Sharif Shaaban 371 Stefan Rooke 372 Alec Birchley 373 Alexander Adams 374 Alisha Davies 375 Amy Gaskin 376 Bree Gatica-Wilcox 377 Caoimhe McKerr 378 Catherine Moore 379 Catryn Williams 380 Chris Williams 381 David Heyburn 382 Elen De Lacy 383 Ember Hilvers 384 Fatima Downing 385 Georgia Pugh 386 Hannah Jones 387 Hibo Asad 388 Jason Coombes 389 Jessica Hey 390 Jessica Powell 391 Joanne Watkins 392 Johnathan M. Evans 393 Laia Fina 394 Laura Gifford 395 Lauren Gilbert 396 Lee Graham 397 Malorie Perry 398 Mari Morgan 399 Matthew Bull 400 Nicole Pacchiarini 401 Noel Craine 402 Sally Corden 403 Sara Kumziene-Summerhayes 404 Sara Rey 405 Sarah Taylor 406 Simon Cottrell 407 Sophie Jones 408 Sue Edwards 409 Tara Annett 410 Alexander J. Trotter 411 Alison E. Mather 412 Alp Aydin 413 Andrew J. Page 414 David J. Baker 415 Ebenezer Foster-Nyarko 416 Gemma L. Kay 417 Justin O’Grady 418 Leonardo de Oliveira Martins 419 Lizzie Meadows 420 Nabil-Fareed Alikhan 421 Sophie J. Prosolek 422 Steven Rudder 423 Thanh Le-Viet 424 Anna Casey 425 Liz Ratcliffe 426 Aditi Singh 427 Arun Mariappan 428 Chris Baxter 429 Clara Radulescu 430 David A. Simpson 431 Deborah Lavin 432 Fiona Rogan 433 Julia Miskelly 434 Marc Fuchs 435 Miao Tang 436 Sílvia F. Carvalho 437 Stephen Bridgett 438 Timofey Skvortsov 439 Zoltan Molnar 440 Newara A. Ramadan 441 Bridget A. Knight 442 Christopher R. Jones 443 Cressida Auckland 444 Helen Morcrette 445 Jennifer Poyner 446 Dianne Irish-Tavares 447 Eric Witele 448 Jennifer Hart 449 Tabitha W. Mahungu 450 Tanzina Haque 451 Yann Bourgeois 452 Christopher Fearn 453 Kate F. Cook 454 Katie F. Loveson 455 Salman Goudarzi 456 Cariad Evans 457 David G. Partridge 458 Kate Johnson 459 Mehmet Yavus 460 Mohammad Raza 461 Craig Mower 462 Paul Baker 463 Sarah Essex 464 Stephen Bonner 465 Leanne J. Murray 466 Louisa K. Watson 467 Steven Liggett 468 Andrew I. Lawton 469 Ronan A. Lyons 470 Brendan A. I. Payne 471 Gary Eltringham 472 Jennifer Collins 473 Sheila Waugh 474 Shirelle Burton-Fanning 475 Yusri Taha 476 Christopher Jeanes 477 Andrea N. Gomes 478 Darren R. Murray 479 Maimuna Kimuli 480 Donald Dobie 481 Paula Ashfield 482 Angus Best 483 Benita Percival 484 Emma Moles-Garcia 485 Fiona Ashford 486 Jeremy Mirza 487 Liam Crawford 488 Megan Mayhew 489 Nicola Cumley 490 Oliver Megram 491 Dan Frampton 492 Judith Heaney 493 Matthew Byott 494 Catherine Houlihan 495 Charlotte A. Williams 496 Eleni Nastouli 497 Helen L. Lowe 498 John A. Hartley 499 Judith Breuer 500 Laurentiu Maftei 501 Leah Ensell 502 Marius Cotic 503 Matteo Mondani 504 Megan Driscoll 505 Nadua Bayzid 506 Rachel J. Williams 507 Sunando Roy 508 Adhyana I. K. Mahanama 509 Buddhini Samaraweera 510 Eleri Wilson-Davies 511 Emanuela Pelosi 512 Helen Umpleby 513 Helen Wheeler 514 Jacqui A. Prieto 515 Kordo Saeed 516 Matthew Harvey 517 Sarah Jeremiah 518 Siona Silviera 519 Stephen Aplin 520 Thea Sass 521 Ben Macklin 522 Dorian Crudgington 523 Liz A. Sheridan 524 Benjamin J. Cogger 525 Cassandra S. Malone 526 Florence Munemo 527 Hannah Huckson 528 Jonathan Lewis 529 Lisa J. Easton 530 Manasa Mutingwende 531 Michelle J. Erkiert 532 Mohammed O. Hassan-Ibrahim 533 Nicola J. Chaloner 534 Olga Podplomyk 535 Paul Randell 536 Roberto Nicodemi 537 Sarah Lowdon 538 Thomas Somassa 539 Alex Richter 540 Andrew Beggs 541 Andrew R. Hesketh 542 Colin P. Smith 543 Giselda Bucca 544 Chris Ruis 545 Claire Cormie 546 Ellen E. Higginson 547 Jamie Young 548 Joana Dias 549 Leanne M. Kermack 550 Mailis Maes 551 Ravi K. Gupta 552 Sally Forrest 553 Sophia T. Girgis 554 Rose K. Davidson 555 Áine O’Toole 556 Andrew Rambaut 557 Ben Jackson 558 Carlos E. Balcazar 559 Daniel Maloney 560 Emily Scher 561 J. T. McCrone 562 Kathleen A. Williamson 563 Michael D. Gallagher 564 Nathan Medd 565 Rachel Colquhoun 566 Thomas D. Stanton 567 Thomas Williams 568 Verity Hill 569 Aaron R. Jeffries 570 Ben Temperton 571 Christine M. Sambles 572 David J. Studholme 573 Joanna Warwick-Dugdale 574 Leigh M. Jackson 575 Michelle L. Michelsen 576 Robin Manley 577 Stephen L. Michell 578 Alistair C. Darby 579 Anita O. Lucaci 580 Charlotte Nelson 581 Claudia Wierzbicki 582 Edith E. Vamos 583 Hermione J. Webster 584 Kathryn A. Jackson 585 Lucille Rainbow 586 Margaret Hughes 587 Mark Whitehead 588 Matthew Gemmell 589 Miren Iturriza-Gomara 590 Richard Eccles 591 Richard Gregory 592 Sam T. Haldenby 593 Steve Paterson 594 Adrienn Angyal 595 Alexander J. Keeley 596 Benjamin H. Foulkes 597 Benjamin B. Lindsey 598 Dennis Wang 599 Hailey R. Hornsby 600 Luke R. Green 601 Manoj Pohare 602 Marta Gallis 603 Matthew D. Parker 604 Max Whiteley 605 Nikki Smith 606 Paige Wolverson 607 Peijun Zhang 608 Samantha E. Hansford 609 Sharon N. Hsu 610 Stavroula F. Louka 611 Thushan I. de Silva 612 Timothy M. Freeman 613 Matilde Mori 614 Emily J. Park 615 Jack D. Hill 616 Jayasree Dey 617 Jonathan Ball 618 Joseph G. Chappell 619 Patrick C. McClure 620 Timothy Byaruhanga 621 Arezou Fanaie 622 Geraldine Yaze 623 Rachel A. Hilson 624 Amy Trebes 625 Angie Green 626 David Buck 627 George MacIntyre-Cockett 628 John A. Todd 629 Andrew R. Bassett 630 Andrew Whitwham 631 Cordelia F. Langford 632 Diana Rajan 633 Dominic Kwiatkowski 634 Ewan M. Harrison 635 Iraad F. Bronner 636 Jaime M. Tovar-Corona 637 Jennifier Liddle 638 Jillian Durham 639 Katherine L. Bellis 640 Kevin Lewis 641 Louise Aigrain 642 Nicholas M. Redshaw 643 Robert M. Davies 644 Robin J. Moll 645 Shane A. McCarthy 646 Stefanie V. Lensing 647 Steven Leonard 648 Ben W. Farr 649 Carol Scott 650 Charlotte Beaver 651 Cristina V. Ariani 652 Danni Weldon 653 David K. Jackson 654 Emma Betteridge 655 Gerry Tonkin-Hill 656 Ian Johnston 657 Inigo Martincorena 658 James Bonfield 659 Jeffrey C. Barrett 660 John Sillitoe 661 Jon-Paul Keatley 662 Karen Oliver 663 Keith James 664 Lesley Shirley 665 Liam Prestwood 666 Luke Foulser 667 Marina Gourtovaia 668 Matthew J. Dorman 669 Michael A. Quail 670 Michael H. Spencer Chapman 671 Naomi R. Park 672 Rich Livett 673 Roberto Amato 674 Sally Kay 675 Scott Goodwin 676 Scott A. J. Thurston 677 Shavanthi Rajatileka 678 Sónia Gonçalves 679 Stephanie Lo 680 Theo Sanderson 681 Alasdair Maclean 682 Emily J. Goldstein 683 Lynne Ferguson 684 Rachael Tomb 685 Jana Catalan 686 Neil Jones 687 John Haughney 688 David L. Robertson 0000-0001-6338-0221 689 Massimo Palmarini 690 Surajit Ray 0000-0003-3965-8136 691 Emma C. Thomson 0000-0003-1482-0889 692 (PITCH Consortium) 693 (The COVID-19 Genomics UK (COG-UK) Consortium) 694 Ronan Lyons 0000-0001-5225-000X 695 66418__30364__1dfaddab9c2d4e83a63e8cc984280d05.pdf 66418.pdf 2024-05-14T15:39:21.8224062 Output 4213204 application/pdf Version of Record true This article is licensed under a Creative Commons Attribution 4.0 International License. true eng https://creativecommons.org/licenses/by/4.0/ |
title |
SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway |
spellingShingle |
SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway Ronan Lyons |
title_short |
SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway |
title_full |
SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway |
title_fullStr |
SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway |
title_full_unstemmed |
SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway |
title_sort |
SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway |
author_id_str_mv |
83efcf2a9dfcf8b55586999d3d152ac6 |
author_id_fullname_str_mv |
83efcf2a9dfcf8b55586999d3d152ac6_***_Ronan Lyons |
author |
Ronan Lyons |
author2 |
Brian J. Willett Joe Grove Oscar A. MacLean Craig Wilkie Giuditta De Lorenzo Wilhelm Furnon Diego Cantoni Sam Scott Nicola Logan Shirin Ashraf Maria Manali Agnieszka Szemiel Vanessa Cowton Elen Vink William T. Harvey Chris Davis Patawee Asamaphan Katherine Smollett Lily Tong Richard Orton Joseph Hughes Poppy Holland Vanessa Silva David J. Pascall Kathryn Puxty Ana da Silva Filipe Gonzalo Yebra Sharif Shaaban Matthew T. G. Holden Rute Maria Pinto Rory Gunson Kate Templeton Pablo R. Murcia Arvind H. Patel Paul Klenerman Susanna Dunachie Susanna Dunachie Paul Klenerman Eleanor Barnes Anthony Brown Sandra Adele Barbara Kronsteiner Sam M. Murray Priyanka Abraham Alexandra Deeks M. Azim Ansari Thushan de Silva Lance Turtle Shona Moore James Austin Alex Richter Christopher Duncan Rebecca Payne Amy Ash Cherian Koshy Beatrix Kele Teresa Cutino-Moguel Derek J. Fairley James P. McKenna Tanya Curran Helen Adams Christophe Fraser David Bonsall Helen Fryer Katrina Lythgoe Laura Thomson Tanya Golubchik Abigail Murray Dawn Singleton Shaun M. Beckwith Anna Mantzouratou Magdalena Barrow Sarah L. Buchan Nicola Reynolds Ben Warne Joshua Maksimovic Karla Spellman Kathryn McCluggage Michaela John Robert Beer Safiah Afifi Sian Morgan Andrew Mack Angela Marchbank Anna Price Arthur Morriss Catherine Bresner Christine Kitchen Ian Merrick Joel Southgate Martyn Guest Owen Jones Robert Munn Thomas R. Connor Thomas Whalley Trudy Workman William Fuller Amita Patel Bindi Patel Gaia Nebbia Jonathan Edgeworth Luke B. Snell Rahul Batra Themoula Charalampous Angela H. Beckett Ekaterina Shelest Samuel C. Robson Anthony P. Underwood Ben E. W. Taylor Corin A. Yeats David M. Aanensen Khalil Abudahab Mirko Menegazzo Amelia Joseph Gemma Clark Hannah C. Howson-Wells Louise Berry Manjinder Khakh Michelle M. Lister Tim Boswell Vicki M. Fleming Christopher W. Holmes Claire L. McMurray Jessica Shaw Julian W. Tang Karlie Fallon Mina Odedra Nicholas J. Willford Paul W. Bird Thomas Helmer Lesley-Anne Williams Nicola Sheriff Sharon Campbell Veena Raviprakash Victoria Blakey Christopher Moore Fei Sang Johnny Debebe Matthew Carlile Matthew W. Loose Nadine Holmes Victoria Wright M. Estee Torok William L. Hamilton Alessandro M. Carabelli Andrew Jermy Beth Blane Carol M. Churcher Catherine Ludden Dinesh Aggarwal Elaine Westwick Ellena Brooks Georgina M. McManus Katerina Galai Ken Smith Kim S. Smith MacGregor Cox Mireille Fragakis Patrick Maxwell Sarah Judges Sharon J. Peacock Theresa Feltwell Anita Kenyon Sahar Eldirdiri Thomas Davis Joshua F. Taylor Ngee Keong Tan Alex E. Zarebski Bernardo Gutierrez Jayna Raghwani Louis du Plessis Moritz U. G. Kraemer Oliver G. Pybus Sarah Francois Stephen W. Attwood Tetyana I. Vasylyeva Aminu S. Jahun Ian G. Goodfellow Iliana Georgana Malte L. Pinckert Myra Hosmillo Rhys Izuagbe Yasmin Chaudhry Felicity Ryan Hannah Lowe Samuel Moses Luke Bedford James S. Cargill Warwick Hughes Jonathan Moore Susanne Stonehouse Divya Shah Jack C. D. Lee Julianne R. Brown Kathryn A. Harris Laura Atkinson Nathaniel Storey Moira J. Spyer Flavia Flaviani Adela Alcolea-Medina Jasveen Sehmi John Ramble Natasha Ohemeng-Kumi Perminder Smith Beatrice Bertolusso Claire Thomas Gabrielle Vernet Jessica Lynch Nathan Moore Nicholas Cortes Rebecca Williams Stephen P. Kidd Lisa J. Levett Monika Pusok Paul R. Grant Stuart Kirk Wendy Chatterton Li Xu-McCrae Darren L. Smith Gregory R. Young Matthew Bashton Katie Kitchman Kavitha Gajee Kirstine Eastick Patrick J. Lillie Phillipa J. Burns William Everson Alison Cox Alison H. Holmes Frances Bolt James R. Price Marcus Pond Paul A. Randell Pinglawathee Madona Siddharth Mookerjee Erik M. Volz Lily Geidelberg Manon Ragonnet-Cronin Olivia Boyd Rob Johnson Cassie F. Pope Adam A. Witney Irene M. Monahan Kenneth G. Laing Katherine L. Smollett Alan McNally Claire McMurray Joanne Stockton Joshua Quick Nicholas J. Loman Radoslaw Poplawski Sam Nicholls Will Rowe Anibolina Castigador Emily Macnaughton Kate El Bouzidi Malur Sudhanva Temi Lampejo Rocio T. Martinez Nunez Cassie Breen Graciela Sluga Karen T. Withell Nicholas W. Machin Ryan P. George Shazaad S. Y. Ahmad David T. Pritchard Debbie Binns Nick Wong Victoria James Cheryl Williams Chris J. Illingworth Chris Jackson Daniela de Angelis David Pascall Afrida Mukaddas Alice Broos Ana da Silva Filipe Daniel Mair David L. Robertson Derek W. Wright Emma C. Thomson Igor Starinskij Ioulia Tsatsani James G. Shepherd Jenna Nichols Joseph Hughes Kyriaki Nomikou Lily Tong Richard J. Orton Sreenu Vattipally William T. Harvey Roy Sanderson Sarah O’Brien Steven Rushton Jon Perkins Rachel Blacow Rory N. Gunson Abbie Gallagher Elizabeth Wastnedge Kate E. Templeton Martin P. McHugh Rebecca Dewar Seb Cotton Lindsay Coupland Rachael Stanley Samir Dervisevic Lewis G. Spurgin Louise Smith Clive Graham Debra Padgett Edward Barton Garren Scott Aidan Cross Mariyam Mirfenderesky Emma Swindells Jane Greenaway Rebecca Denton-Smith Robyn Turnbull Giles Idle Kevin Cole Amy Hollis Andrew Nelson Clare M. McCann John H. Henderson Matthew R. Crown Wen C. Yew William Stanley Nichola Duckworth Phillip Clarke Sarah Walsh Tim J. Sloan Kelly Bicknell Robert Impey Sarah Wyllie Scott Elliott Sharon Glaysher Declan T. Bradley Nicholas F. Killough Tim Wyatt Andrew Bosworth Barry B. Vipond Clare Pearson Elias Allara Esther Robinson Hannah M. Pymont Husam Osman Peter Muir Richard Hopes Stephanie Hutchings Martin D. Curran Surendra Parmar Alicia Thornton Angie Lackenby Chloe Bishop David Bibby David Lee Eileen Gallagher Gavin Dabrera Ian Harrison Jonathan Hubb Katherine A. Twohig Meera Chand Nicholas Ellaby Nikos Manesis Richard Myers Steven Platt Tamyo Mbisa Vicki Chalker Gonzalo Yebra Matthew T. G. Holden Sharif Shaaban Stefan Rooke Alec Birchley Alexander Adams Alisha Davies Amy Gaskin Bree Gatica-Wilcox Caoimhe McKerr Catherine Moore Catryn Williams Chris Williams David Heyburn Elen De Lacy Ember Hilvers Fatima Downing Georgia Pugh Hannah Jones Hibo Asad Jason Coombes Jessica Hey Jessica Powell Joanne Watkins Johnathan M. Evans Laia Fina Laura Gifford Lauren Gilbert Lee Graham Malorie Perry Mari Morgan Matthew Bull Nicole Pacchiarini Noel Craine Sally Corden Sara Kumziene-Summerhayes Sara Rey Sarah Taylor Simon Cottrell Sophie Jones Sue Edwards Tara Annett Alexander J. Trotter Alison E. Mather Alp Aydin Andrew J. Page David J. Baker Ebenezer Foster-Nyarko Gemma L. Kay Justin O’Grady Leonardo de Oliveira Martins Lizzie Meadows Nabil-Fareed Alikhan Sophie J. Prosolek Steven Rudder Thanh Le-Viet Anna Casey Liz Ratcliffe Aditi Singh Arun Mariappan Chris Baxter Clara Radulescu David A. Simpson Deborah Lavin Fiona Rogan Julia Miskelly Marc Fuchs Miao Tang Sílvia F. Carvalho Stephen Bridgett Timofey Skvortsov Zoltan Molnar Newara A. Ramadan Bridget A. Knight Christopher R. Jones Cressida Auckland Helen Morcrette Jennifer Poyner Dianne Irish-Tavares Eric Witele Jennifer Hart Tabitha W. Mahungu Tanzina Haque Yann Bourgeois Christopher Fearn Kate F. Cook Katie F. Loveson Salman Goudarzi Cariad Evans David G. Partridge Kate Johnson Mehmet Yavus Mohammad Raza Craig Mower Paul Baker Sarah Essex Stephen Bonner Leanne J. Murray Louisa K. Watson Steven Liggett Andrew I. Lawton Ronan A. Lyons Brendan A. I. Payne Gary Eltringham Jennifer Collins Sheila Waugh Shirelle Burton-Fanning Yusri Taha Christopher Jeanes Andrea N. Gomes Darren R. Murray Maimuna Kimuli Donald Dobie Paula Ashfield Angus Best Benita Percival Emma Moles-Garcia Fiona Ashford Jeremy Mirza Liam Crawford Megan Mayhew Nicola Cumley Oliver Megram Dan Frampton Judith Heaney Matthew Byott Catherine Houlihan Charlotte A. Williams Eleni Nastouli Helen L. Lowe John A. Hartley Judith Breuer Laurentiu Maftei Leah Ensell Marius Cotic Matteo Mondani Megan Driscoll Nadua Bayzid Rachel J. Williams Sunando Roy Adhyana I. K. Mahanama Buddhini Samaraweera Eleri Wilson-Davies Emanuela Pelosi Helen Umpleby Helen Wheeler Jacqui A. Prieto Kordo Saeed Matthew Harvey Sarah Jeremiah Siona Silviera Stephen Aplin Thea Sass Ben Macklin Dorian Crudgington Liz A. Sheridan Benjamin J. Cogger Cassandra S. Malone Florence Munemo Hannah Huckson Jonathan Lewis Lisa J. Easton Manasa Mutingwende Michelle J. Erkiert Mohammed O. Hassan-Ibrahim Nicola J. Chaloner Olga Podplomyk Paul Randell Roberto Nicodemi Sarah Lowdon Thomas Somassa Alex Richter Andrew Beggs Andrew R. Hesketh Colin P. Smith Giselda Bucca Chris Ruis Claire Cormie Ellen E. Higginson Jamie Young Joana Dias Leanne M. Kermack Mailis Maes Ravi K. Gupta Sally Forrest Sophia T. Girgis Rose K. Davidson Áine O’Toole Andrew Rambaut Ben Jackson Carlos E. Balcazar Daniel Maloney Emily Scher J. T. McCrone Kathleen A. Williamson Michael D. Gallagher Nathan Medd Rachel Colquhoun Thomas D. Stanton Thomas Williams Verity Hill Aaron R. Jeffries Ben Temperton Christine M. Sambles David J. Studholme Joanna Warwick-Dugdale Leigh M. Jackson Michelle L. Michelsen Robin Manley Stephen L. Michell Alistair C. Darby Anita O. Lucaci Charlotte Nelson Claudia Wierzbicki Edith E. Vamos Hermione J. Webster Kathryn A. Jackson Lucille Rainbow Margaret Hughes Mark Whitehead Matthew Gemmell Miren Iturriza-Gomara Richard Eccles Richard Gregory Sam T. Haldenby Steve Paterson Adrienn Angyal Alexander J. Keeley Benjamin H. Foulkes Benjamin B. Lindsey Dennis Wang Hailey R. Hornsby Luke R. Green Manoj Pohare Marta Gallis Matthew D. Parker Max Whiteley Nikki Smith Paige Wolverson Peijun Zhang Samantha E. Hansford Sharon N. Hsu Stavroula F. Louka Thushan I. de Silva Timothy M. Freeman Matilde Mori Emily J. Park Jack D. Hill Jayasree Dey Jonathan Ball Joseph G. Chappell Patrick C. McClure Timothy Byaruhanga Arezou Fanaie Geraldine Yaze Rachel A. Hilson Amy Trebes Angie Green David Buck George MacIntyre-Cockett John A. Todd Andrew R. Bassett Andrew Whitwham Cordelia F. Langford Diana Rajan Dominic Kwiatkowski Ewan M. Harrison Iraad F. Bronner Jaime M. Tovar-Corona Jennifier Liddle Jillian Durham Katherine L. Bellis Kevin Lewis Louise Aigrain Nicholas M. Redshaw Robert M. Davies Robin J. Moll Shane A. McCarthy Stefanie V. Lensing Steven Leonard Ben W. Farr Carol Scott Charlotte Beaver Cristina V. Ariani Danni Weldon David K. Jackson Emma Betteridge Gerry Tonkin-Hill Ian Johnston Inigo Martincorena James Bonfield Jeffrey C. Barrett John Sillitoe Jon-Paul Keatley Karen Oliver Keith James Lesley Shirley Liam Prestwood Luke Foulser Marina Gourtovaia Matthew J. Dorman Michael A. Quail Michael H. Spencer Chapman Naomi R. Park Rich Livett Roberto Amato Sally Kay Scott Goodwin Scott A. J. Thurston Shavanthi Rajatileka Sónia Gonçalves Stephanie Lo Theo Sanderson Alasdair Maclean Emily J. Goldstein Lynne Ferguson Rachael Tomb Jana Catalan Neil Jones John Haughney David L. Robertson Massimo Palmarini Surajit Ray Emma C. Thomson (PITCH Consortium) (The COVID-19 Genomics UK (COG-UK) Consortium) Ronan Lyons |
format |
Journal article |
container_title |
Nature Microbiology |
container_volume |
7 |
container_issue |
8 |
container_start_page |
1161 |
publishDate |
2022 |
institution |
Swansea University |
issn |
2058-5276 |
doi_str_mv |
10.1038/s41564-022-01143-7 |
publisher |
Springer Science and Business Media LLC |
college_str |
Faculty of Medicine, Health and Life Sciences |
hierarchytype |
|
hierarchy_top_id |
facultyofmedicinehealthandlifesciences |
hierarchy_top_title |
Faculty of Medicine, Health and Life Sciences |
hierarchy_parent_id |
facultyofmedicinehealthandlifesciences |
hierarchy_parent_title |
Faculty of Medicine, Health and Life Sciences |
department_str |
Swansea University Medical School - Health Data Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Health Data Science |
document_store_str |
1 |
active_str |
0 |
description |
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. |
published_date |
2022-08-01T12:09:45Z |
_version_ |
1802740574885773312 |
score |
11.036815 |