TY - JOUR
T1 - SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway
AU - The COVID-19 Genomics UK (COG-UK) Consortium
AU - PITCH Consortium
AU - Willett, Brian J.
AU - Grove, Joe
AU - MacLean, Oscar A.
AU - Wilkie, Craig
AU - De Lorenzo, Giuditta
AU - Furnon, Wilhelm
AU - Cantoni, Diego
AU - Scott, Sam
AU - Logan, Nicola
AU - Ashraf, Shirin
AU - Manali, Maria
AU - Szemiel, Agnieszka
AU - Cowton, Vanessa
AU - Vink, Elen
AU - Harvey, William T.
AU - Davis, Chris
AU - Asamaphan, Patawee
AU - Smollett, Katherine
AU - Tong, Lily
AU - Orton, Richard J.
AU - Hughes, Joseph
AU - Holland, Poppy
AU - Silva, Vanessa
AU - Pascall, David J.
AU - Puxty, Kathryn
AU - da Silva Filipe, Ana
AU - Yebra, Gonzalo
AU - Shaaban, Sharif
AU - Holden, Matthew T.G.
AU - Pinto, Rute Maria
AU - Gunson, Rory
AU - Templeton, Kate
AU - Murcia, Pablo R.
AU - Patel, Arvind H.
AU - Klenerman, Paul
AU - Dunachie, Susanna
AU - Klenerman, Paul
AU - Barnes, Eleanor
AU - Brown, Anthony
AU - Adele, Sandra
AU - Kronsteiner, Barbara
AU - Murray, Sam M.
AU - Abraham, Priyanka
AU - Deeks, Alexandra
AU - Ansari, M. Azim
AU - de Silva, Thushan
AU - Turtle, Lance
AU - Moore, Shona
AU - Austin, James
AU - Gutierrez, Bernardo
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/8/1
Y1 - 2022/8/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85133843705&partnerID=8YFLogxK
U2 - 10.1038/s41564-022-01143-7
DO - 10.1038/s41564-022-01143-7
M3 - Artículo
C2 - 35798890
AN - SCOPUS:85133843705
SN - 2058-5276
VL - 7
SP - 1161
EP - 1179
JO - Nature Microbiology
JF - Nature Microbiology
IS - 8
ER -
