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Cited by 931SARS-CoV-2 and COVID-19 Researchvaccines and immunoinformatics approachesAnimal Virus Infections Studies

The DOI matches its Crossref record; 67 of the 73 references it cites were found in a registry or an index.

SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses

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DOI 10.1016/j.cell.2021.12.046PMC PMC8723827
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Abstract

November 2021, the sequence of a new SARS-CoV-2 viral isolate Omicron-B.1.1.529 was announced, containing far more mutations in Spike (S) than previously reported variants. Neutralization titers of Omicron by sera from vaccinees and convalescent subjects infected with early pandemic Alpha, Beta, Gamma, or Delta are substantially reduced, or the sera failed to neutralize. Titers against Omicron are boosted by third vaccine doses and are high in both vaccinated individuals and those infected by Delta. Mutations in Omicron knock out or substantially reduce neutralization by most of the large panel of potent monoclonal antibodies and antibodies under commercial development. Omicron S has structural changes from earlier viruses and uses mutations that confer tight binding to ACE2 to unleash evolution driven by immune escape. This leads to a large number of mutations in the ACE2 binding site and rebalances receptor affinity to that of earlier pandemic viruses.

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Graphical abstract
Graphical abstract CC BY · PubMed Central
Figure 1 Sarbecovirus RBD sequence analysis Shown with Alpha, Beta, Delta, and Omicron variants (Omicron repeated on the lower line for clarity). Binding sites for the early pandemic potent antibodies (Dejnirattisai et al., 2021a) and the potent Beta antibodies (Liu et al., 2021b) are depicted using iron heat colors (black < straw < yellow < white) to indicate relative levels of antibody contact and commercial antibody contacts are depicted with the pairs of antibodies in red and blue (purple denotes common interactions). Totally conserved residues are boxed on a red background on the upper rows, while on the final row Omicron mutations are boxed in red. Secondary elements are denoted above the alignment. Figure produced in part using ESPript (Robert and Gouet, 2014).
Figure 1 Sarbecovirus RBD sequence analysis Shown with Alpha, Beta, Delta, and Omicron variants (Omicron repeated on the lower line for clarity). Binding sites for the early pandemic potent antibodies (Dejnirattisai et al., 2021a) and the potent Beta antibodies (Liu et al., 2021b) are depicted using iron heat colors (black < straw < yellow < white) to indicate relative levels of antibody contact and commercial antibody contacts are depicted with the pairs of antibodies in red and blue (purple denotes common interactions). Totally conserved residues are boxed on a red background on the upper rows, while on the final row Omicron mutations are boxed in red. Secondary elements are denoted above the alignment. Figure produced in part using ESPript (Robert and Gouet, 2014).CC BY · PubMed Central
Figure 2 Distribution of Omicron changes (A) Trimeric S model depicted as a gray surface with one monomer highlighted in pale blue, ACE2 binding site in green and changes in Omicron shown in red, left side view, right top view. (B) RBD depicted as a gray surface with the ACE2 footprint in dark gray and changes in Omicron in red, left: top view, right: front and back views. Epitopes are labeled according to the torso analogy and mutations labeled. (C–F) Top view of RBD depicted as a gray surface with the following: (C) ACE2 binding site in green. (D) Alpha change in yellow, (E) Beta changes in cyan, and (F) Delta changes in purple. Figure produced using chimeraX (Pettersen et al., 2021). Related to Figure S1.
Figure 2 Distribution of Omicron changes (A) Trimeric S model depicted as a gray surface with one monomer highlighted in pale blue, ACE2 binding site in green and changes in Omicron shown in red, left side view, right top view. (B) RBD depicted as a gray surface with the ACE2 footprint in dark gray and changes in Omicron in red, left: top view, right: front and back views. Epitopes are labeled according to the torso analogy and mutations labeled. (C–F) Top view of RBD depicted as a gray surface with the following: (C) ACE2 binding site in green. (D) Alpha change in yellow, (E) Beta changes in cyan, and (F) Delta changes in purple. Figure produced using chimeraX (Pettersen et al., 2021). Related to Figure S1.CC BY · PubMed Central
Figure S1 Omicron mutations, related to Figures 2 and 7E (A) Number of sequenced mutations per position. The line shows the number of mutations per residue, for high to low along the spike protein. In green are mutations D614G, which is fixed from early virus evolution and position 498, which became dominant only in Omicron. Red are mutations in Omicron identified earlier in multiple linages and blue are mutations with Omicron being the only lineage. (B) Location of the S371L, S373P, and S375F mutations in the context of the conformation change occurring on binding lipid. Cartoons of the apo (blue) and lipid bound (pink) early pandemic RBD are shown. The lipid is shown in red.
Figure S1 Omicron mutations, related to Figures 2 and 7E (A) Number of sequenced mutations per position. The line shows the number of mutations per residue, for high to low along the spike protein. In green are mutations D614G, which is fixed from early virus evolution and position 498, which became dominant only in Omicron. Red are mutations in Omicron identified earlier in multiple linages and blue are mutations with Omicron being the only lineage. (B) Location of the S371L, S373P, and S375F mutations in the context of the conformation change occurring on binding lipid. Cartoons of the apo (blue) and lipid bound (pink) early pandemic RBD are shown. The lipid is shown in red.CC BY · PubMed Central
Figure 3 Neutralization assays against Omicron (A–H) FRNT50 values for the indicated viruses using serum from convalescent subjects previously infected with (A) early pandemic virus (n = 32), (B) Alpha (n = 18), (C) Beta (n = 14), (D) Gamma (n = 16), (E) Delta (n = 19), (F) Delta before vaccination or Delta after vaccination (n = 17), (G) before and after the third dose of AZD1222 (n = 41), and (H) 4 weeks, 6 months after the second dose, before the third, and after the third dose of BNT162b2 (n = 20). In (A–E) comparison is made with neutralization titers to Victoria, Alpha, Beta, Gamma, and Delta previously reported in Dejnirattisai et al. (2021a, 2021b), Supasa et al. (2021), Zhou et al. (2021), and Liu et al. (2021b), in (G) the data points for Victoria and Delta titers on BNT162b2 are taken from Flaxman et al. (2021). Geometric mean titers are shown above each column. The Wilcoxon matched-pairs signed rank test was used for the analysis, and two-tailed p values were calculated.
Figure 3 Neutralization assays against Omicron (A–H) FRNT50 values for the indicated viruses using serum from convalescent subjects previously infected with (A) early pandemic virus (n = 32), (B) Alpha (n = 18), (C) Beta (n = 14), (D) Gamma (n = 16), (E) Delta (n = 19), (F) Delta before vaccination or Delta after vaccination (n = 17), (G) before and after the third dose of AZD1222 (n = 41), and (H) 4 weeks, 6 months after the second dose, before the third, and after the third dose of BNT162b2 (n = 20). In (A–E) comparison is made with neutralization titers to Victoria, Alpha, Beta, Gamma, and Delta previously reported in Dejnirattisai et al. (2021a, 2021b), Supasa et al. (2021), Zhou et al. (2021), and Liu et al. (2021b), in (G) the data points for Victoria and Delta titers on BNT162b2 are taken from Flaxman et al. (2021). Geometric mean titers are shown above each column. The Wilcoxon matched-pairs signed rank test was used for the analysis, and two-tailed p values were calculated.CC BY · PubMed Central
Figure S2 FRNT50 values for 7 cases of Delta infection before and after vaccination, related to Figure 4
Figure S2 FRNT50 values for 7 cases of Delta infection before and after vaccination, related to Figure 4CC BY · PubMed Central
Figure 4 mAb neutralization curves (A–C) FRNT curves for mAb from (A) early pandemic, (B) Beta infected cases or (C) commercial sources. Omicron neutralization is compared with curves for Victoria, Alpha, Beta, Gamma, and Delta, which have been previously reported (Dejnirattisai et al., 2021a, 2021b; Supasa et al., 2021; Zhou et al., 2021; Liu et al., 2021b). Neutralization titers are reported in Table S1. Related to Figure S2.
Figure 4 mAb neutralization curves (A–C) FRNT curves for mAb from (A) early pandemic, (B) Beta infected cases or (C) commercial sources. Omicron neutralization is compared with curves for Victoria, Alpha, Beta, Gamma, and Delta, which have been previously reported (Dejnirattisai et al., 2021a, 2021b; Supasa et al., 2021; Zhou et al., 2021; Liu et al., 2021b). Neutralization titers are reported in Table S1. Related to Figure S2.CC BY · PubMed Central
Figure 5 Relative antibody contact (A–D) RBD surface produced in PyMOL and rendered in mabscape using iron heat colors (gray < blue < glowing red < yellow < white) to indicate relative levels of antibody contact. Antibody contact is calculated for each surface vertex as the number of antibodies within a 10 Å radius by their known or predicted positions from earlier mapping studies (Dejnirattisai et al., 2021a; Liu et al., 2021b). Outward facing cones are placed at the nearest vertex to each mutated residue on the RBD surface. Drawn back and front views for (A) all RBD-reactive antibodies isolated from early pandemic, (B)strongly neutralizing antibodies (<100 ng/mL) from early pandemic. (C) strongly neutralizing antibodies isolated from Beta infected cases and (D) therapeutic antibodies for clinical use (from PDB: 7BEP, 6XDG, 7L7E, 7KMG, 7KMH). (E–G) Front (right) and back (left) views of the RBD drawn as a gray surface with Omicron changes highlighted in magenta and glycans drawn as sticks. (E–G) (E) Outline footprints of a selection of early pandemic mAbs: 58, 88, 222, 253, and 278 are shown by balls representing the centroid of H3 (red), H1(salmon). L3 (blue) and L1 (slate) loops joined by yellow or cyan sticks. (F) As for (E), showing a selection of Beta antibodies: 27, 47, 49, and 53. (G) As for (E) showing a selection of commercial antibodies: REGN10933, REGN10987, S309, AZD1061, AZD8895, LY-CoV555, and LY-CoV016. Related to Figures S3, S4, and S5.
Figure 5 Relative antibody contact (A–D) RBD surface produced in PyMOL and rendered in mabscape using iron heat colors (gray < blue < glowing red < yellow < white) to indicate relative levels of antibody contact. Antibody contact is calculated for each surface vertex as the number of antibodies within a 10 Å radius by their known or predicted positions from earlier mapping studies (Dejnirattisai et al., 2021a; Liu et al., 2021b). Outward facing cones are placed at the nearest vertex to each mutated residue on the RBD surface. Drawn back and front views for (A) all RBD-reactive antibodies isolated from early pandemic, (B)strongly neutralizing antibodies (<100 ng/mL) from early pandemic. (C) strongly neutralizing antibodies isolated from Beta infected cases and (D) therapeutic antibodies for clinical use (from PDB: 7BEP, 6XDG, 7L7E, 7KMG, 7KMH). (E–G) Front (right) and back (left) views of the RBD drawn as a gray surface with Omicron changes highlighted in magenta and glycans drawn as sticks. (E–G) (E) Outline footprints of a selection of early pandemic mAbs: 58, 88, 222, 253, and 278 are shown by balls representing the centroid of H3 (red), H1(salmon). L3 (blue) and L1 (slate) loops joined by yellow or cyan sticks. (F) As for (E), showing a selection of Beta antibodies: 27, 47, 49, and 53. (G) As for (E) showing a selection of commercial antibodies: REGN10933, REGN10987, S309, AZD1061, AZD8895, LY-CoV555, and LY-CoV016. Related to Figures S3, S4, and S5.CC BY · PubMed Central
Figure S3 Binding modes of early pandemic mAbs and their contacts to Omicron mutation sites, related to Figure 5 (A) Fabs are drawn as ribbons with the heavy chains in red and light chains in blue and RBDs as gray ribbon or surface representation with Omicron mutation sites highlighted in magenta. Side chains are shown as sticks and hydrogen bonds as dashed lines. (A) Fab 58 does not make any close contacts with the Omicron mutation sites. (B–F) Binding modes and contacts with Omicron mutation sites of Fabs 170, 222, 253, 278, and 316, respectively.
Figure S3 Binding modes of early pandemic mAbs and their contacts to Omicron mutation sites, related to Figure 5 (A) Fabs are drawn as ribbons with the heavy chains in red and light chains in blue and RBDs as gray ribbon or surface representation with Omicron mutation sites highlighted in magenta. Side chains are shown as sticks and hydrogen bonds as dashed lines. (A) Fab 58 does not make any close contacts with the Omicron mutation sites. (B–F) Binding modes and contacts with Omicron mutation sites of Fabs 170, 222, 253, 278, and 316, respectively.CC BY · PubMed Central
Figure S4 Binding modes of Beta mAbs and their contacts to Omicron mutation sites, related to Figure 5 (A and B) The drawing and coloring schemes are same as in Figure S3. These are structures of Beta-RBD/Beta-Fab complexes. (A) Beta-24 and (B) Beta-54, examples of Beta mAbs targeting the N501Y mutation site. (C) Beta-38, a representative of Beta mAbs targeting the E484K mutation site. (D) Beta-29, a K417N/T-dependent Beta mAb. (E) Beta-44 binds at the top of left shoulder and is sensitive to T478K mutation. (F–I) Beta-27, -47, -49, and -53, respectively. These four Beta mAbs neutralize all the previous variants of concern, as well as the early pandemic Wuhan strain.
Figure S4 Binding modes of Beta mAbs and their contacts to Omicron mutation sites, related to Figure 5 (A and B) The drawing and coloring schemes are same as in Figure S3. These are structures of Beta-RBD/Beta-Fab complexes. (A) Beta-24 and (B) Beta-54, examples of Beta mAbs targeting the N501Y mutation site. (C) Beta-38, a representative of Beta mAbs targeting the E484K mutation site. (D) Beta-29, a K417N/T-dependent Beta mAb. (E) Beta-44 binds at the top of left shoulder and is sensitive to T478K mutation. (F–I) Beta-27, -47, -49, and -53, respectively. These four Beta mAbs neutralize all the previous variants of concern, as well as the early pandemic Wuhan strain.CC BY · PubMed Central
Figure S5 Binding modes of the therapeutic mAbs and their contacts to Omicron mutation sites, related to Figure 5 (A–E) The drawing and coloring schemes are same as in Figure S3. (A) REGN10987 and REGN10933, (B) AZD8895 and AZD1061, (C) Vir S309, (D) LY-CoV016, and (E) LY-CoV555.
Figure S5 Binding modes of the therapeutic mAbs and their contacts to Omicron mutation sites, related to Figure 5 (A–E) The drawing and coloring schemes are same as in Figure S3. (A) REGN10987 and REGN10933, (B) AZD8895 and AZD1061, (C) Vir S309, (D) LY-CoV016, and (E) LY-CoV555.CC BY · PubMed Central
Figure S6 SPR measurement and crystal structure of the Omicron RBD complexed with Beta-55 and EY6A Fabs, related to Figure 7 (A) SPR measurements. (B) Ternary complex of the Omicron RBD (gray)/Beta-55 (heavy chain red, light chain blue)/EY6A (heavy chain salmon, light chain cyan). (C) Electron density map showing the density for the mutated residues at 446, 498, 501, and 505, and their interactions with the CDR-H3 of Beta-55. (D and E) Comparison of the slightly different binding mode of Beta-55 to Beta-24 (cyan in D) and Beta-40 (cyan in E), the close-up boxes show details of the interactions with Beta-24 and Beta-40 explaining the knockout of Beta-24 and the resilience of Beta-40.
Figure S6 SPR measurement and crystal structure of the Omicron RBD complexed with Beta-55 and EY6A Fabs, related to Figure 7 (A) SPR measurements. (B) Ternary complex of the Omicron RBD (gray)/Beta-55 (heavy chain red, light chain blue)/EY6A (heavy chain salmon, light chain cyan). (C) Electron density map showing the density for the mutated residues at 446, 498, 501, and 505, and their interactions with the CDR-H3 of Beta-55. (D and E) Comparison of the slightly different binding mode of Beta-55 to Beta-24 (cyan in D) and Beta-40 (cyan in E), the close-up boxes show details of the interactions with Beta-24 and Beta-40 explaining the knockout of Beta-24 and the resilience of Beta-40.CC BY · PubMed Central
Figure 6 Affinity driving mutations in Omicron RBD have previously been identified by in vitro evolution for tighter binding (A) Analysis of the occurrence and prevalence of Omicron-variant mutations. The background is colored according to S-protein functional domains. The four positions critical for the high affinity of RBD-62 are highlighted in bold. Mutation frequencies within individual lineages are denoted in green (100%–75%), blue (75%–50%), and magenta (50%–25%). Information about the distribution and frequency of S-protein mutations and the spatiotemporal characterization of SARS-CoV-2 lineages were retrieved from www.outbreak.info (Mullen et al., 2020) and GISAID database (Elbe and Buckland-Merrett, 2017).∗ Same evolutionary origin, anumber of evolutionary non-related lineages with given or similar mutation (Zahradnik et al., 2021c), blog(10) number of the observed Omicron mutation at the given position as determined on 14th November 2021, csame as bbut total log(10) number of changes at the given position. dFold-change in binding as determined by yeast-surface display. Fold-change is the ratio between original RBD KD and the mutant RBD KD for binding human ACE2. (B) Comparison of fold-change in binding affinity among selected mutations and their combinations as determined by titrating ACE2 on yeast surface displayed RBD mutations. For Omicron, yeast titration is denoted in violet, SPR (this study) is dark red, SPR as determined in Cameroni et al. (2021) is gray and ELISA as determined in Schubert et al. (2021) is in orange. Data denoted by black dots have been reported previously (Zahradník et al., 2021b). (C) RBD-62 (blue)/ACE2 (green) structure (PDB: 7BH9) overlaid on Omicron RBD structure (orange) as determined bound to Beta-55. All Omicron mutations are shown, overlaid on relevant RBD-62 mutations. (D) Electrostatic potential surface depictions calculated using PyMol. Blue is positive and red negative potential (scale bar shown below).
Figure 6 Affinity driving mutations in Omicron RBD have previously been identified by in vitro evolution for tighter binding (A) Analysis of the occurrence and prevalence of Omicron-variant mutations. The background is colored according to S-protein functional domains. The four positions critical for the high affinity of RBD-62 are highlighted in bold. Mutation frequencies within individual lineages are denoted in green (100%–75%), blue (75%–50%), and magenta (50%–25%). Information about the distribution and frequency of S-protein mutations and the spatiotemporal characterization of SARS-CoV-2 lineages were retrieved from www.outbreak.info (Mullen et al., 2020) and GISAID database (Elbe and Buckland-Merrett, 2017).∗ Same evolutionary origin, anumber of evolutionary non-related lineages with given or similar mutation (Zahradnik et al., 2021c), blog(10) number of the observed Omicron mutation at the given position as determined on 14th November 2021, csame as bbut total log(10) number of changes at the given position. dFold-change in binding as determined by yeast-surface display. Fold-change is the ratio between original RBD KD and the mutant RBD KD for binding human ACE2. (B) Comparison of fold-change in binding affinity among selected mutations and their combinations as determined by titrating ACE2 on yeast surface displayed RBD mutations. For Omicron, yeast titration is denoted in violet, SPR (this study) is dark red, SPR as determined in Cameroni et al. (2021) is gray and ELISA as determined in Schubert et al. (2021) is in orange. Data denoted by black dots have been reported previously (Zahradník et al., 2021b). (C) RBD-62 (blue)/ACE2 (green) structure (PDB: 7BH9) overlaid on Omicron RBD structure (orange) as determined bound to Beta-55. All Omicron mutations are shown, overlaid on relevant RBD-62 mutations. (D) Electrostatic potential surface depictions calculated using PyMol. Blue is positive and red negative potential (scale bar shown below).CC BY · PubMed Central
Figure 7 Antigenic map from neutralization data for Omicron (A) Neutralization data (log titers) showing sera as columns against challenge variants as rows. Sera are grouped into blocks according to the eliciting variant. The reference neutralization titer for each block is calculated as the average of all titers when challenged with the variant that elicited the serum. In the case of vaccine sera this was taken as the average of all best neutralization titers. Therefore, colors within a single block express the relative neutralization titer with respect to this reference. (B) Shows an example of the equivalent model generated from one run of antigenic map refinement using the same reference offsets as calculated for (A). (C) Shows a view of the three-dimensional antigenic map for variants of concern. The distance between two points corresponds to the drop-off in neutralization titer used in (B). (D) Same antigenic space as (C) but rotated 90°, to look downward form Omicron. (E) Overlay of the X-ray structure of Omicron (red) on the early pandemic (Wuhan) RBD (gray) and the predicted model of the Omicron RBD in black, drawn as cartoons. The structural change effected by the S371L, S373P, and S375F mutations is shown enlarged in the inset. (F) X-ray structure of ternary complex of Omicron RBD with Beta-55 and EY6A Fabs. The Omicron RBD is shown as a gray semi-transparent surface with mutated residues in magenta. Fabs are drawn as cartoons, heavy chain in magenta and light chain in blue. Related to Figures S1 and S6 and Video S1.
Figure 7 Antigenic map from neutralization data for Omicron (A) Neutralization data (log titers) showing sera as columns against challenge variants as rows. Sera are grouped into blocks according to the eliciting variant. The reference neutralization titer for each block is calculated as the average of all titers when challenged with the variant that elicited the serum. In the case of vaccine sera this was taken as the average of all best neutralization titers. Therefore, colors within a single block express the relative neutralization titer with respect to this reference. (B) Shows an example of the equivalent model generated from one run of antigenic map refinement using the same reference offsets as calculated for (A). (C) Shows a view of the three-dimensional antigenic map for variants of concern. The distance between two points corresponds to the drop-off in neutralization titer used in (B). (D) Same antigenic space as (C) but rotated 90°, to look downward form Omicron. (E) Overlay of the X-ray structure of Omicron (red) on the early pandemic (Wuhan) RBD (gray) and the predicted model of the Omicron RBD in black, drawn as cartoons. The structural change effected by the S371L, S373P, and S375F mutations is shown enlarged in the inset. (F) X-ray structure of ternary complex of Omicron RBD with Beta-55 and EY6A Fabs. The Omicron RBD is shown as a gray semi-transparent surface with mutated residues in magenta. Fabs are drawn as cartoons, heavy chain in magenta and light chain in blue. Related to Figures S1 and S6 and Video S1.CC BY · PubMed Central

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  1. Cele, 2021, SARS-CoV-2 evolved during advanced HIV disease immunosuppression has Beta-like escape of vaccine and Delta infection elicited immunity, medRxiv, medRxiv
  2. Schubert, 2021, Human serum from SARS-CoV-2 vaccinated and COVID-19 patients shows reduced binding to the RBD of SARS-CoV-2 Omicron variant in comparison to the original Wuhan strain and the Beta and Delta variants, medRxiv

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Dejnirattisai, W., Huo, J., Zhou, D., Zahradník, J., Supasa, P., Liu, C., Duyvesteyn, H. M. E., Ginn, H. M., Mentzer, A. J., Tuekprakhon, A., Nutalai, R., Wang, B., Dijokaite, A., Khan, S., Avinoam, O., Bahar, M., Skelly, D., Adele, S., Johnson, S. A., Amini, A., Ritter, T. G., Mason, C., Dold, C., Pan, D., Assadi, S., Bellass, A., Omo-Dare, N., Koeckerling, D., Flaxman, A., Jenkin, D., Aley, P. K., Voysey, M., Costa Clemens, S. A., Naveca, F. G., Nascimento, V., Nascimento, F., Fernandes da Costa, C., Resende, P. C., Pauvolid-Correa, A., Siqueira, M. M., Baillie, V., Serafin, N., Kwatra, G., Da Silva, K., Madhi, S. A., Nunes, M. C., Malik, T., Openshaw, P. J. M., Baillie, J. K., Semple, M. G., Townsend, A. R., Huang, K.-Y. A., Tan, T. K., Carroll, M. W., Klenerman, P., Barnes, E., Dunachie, S. J., Constantinides, B., Webster, H., Crook, D., Pollard, A. J., Lambe, T., Conlon, C., Deeks, A. S., Frater, J., Frending, L., Gardiner, S., Jämsén, A., Jeffery, K., Malone, T., Phillips, E., Rothwell, L., Stafford, L., Baillie, J. K., Semple, M. G., Openshaw, P. J., Carson, G., Alex, B., Andrikopoulos, P., Bach, B., Barclay, W. S., Bogaert, D., Chand, M., Chechi, K., Cooke, G. S., da Silva Filipe, A., de Silva, T., Docherty, A. B., dos Santos Correia, G., Dumas, M.-E., Dunning, J., Fletcher, T., Green, C. A., Greenhalf, W., Griffin, J. L., Gupta, R. K., Harrison, E. M., Hiscox, J. A., Wai Ho, A. Y., Horby, P. W., Ijaz, S., Khoo, S., Klenerman, P., Law, A., Lewis, M. R., Liggi, S., Lim, W. S., Maslen, L., Mentzer, A. J., Merson, L., Meynert, A. M., Moore, S. C., Noursadeghi, M., Olanipekun, M., Osagie, A., Palmarini, M., Palmieri, C., Paxton, W. A., Pollakis, G., Price, N., Rambaut, A., Robertson, D. L., Russell, C. D., Sancho-Shimizu, V., Sands, C. J., Scott, J. T., Sigfrid, L., Solomon, T., Sriskandan, S., Stuart, D., Summers, C., Swann, O. V., Takats, Z., Takis, P., Tedder, R. S., Thompson, A. R., Thomson, E. C., Thwaites, R. S., Turtle, L. C., Zambon, M., Hardwick, H., Donohue, C., Griffiths, F., Oosthuyzen, W., Donegan, C., Spencer, R. G., Norman, L., Pius, R., Drake, T. M., Fairfield, C. J., Knight, S. R., Mclean, K. A., Murphy, D., Shaw, C. A., Dalton, J., Girvan, M., Saviciute, E., Roberts, S., Harrison, J., Marsh, L., Connor, M., Halpin, S., Jackson, C., Gamble, C., Plotkin, D., Lee, J., Leeming, G., Law, A., Wham, M., Clohisey, S., Hendry, R., Scott-Brown, J., Shaw, V., McDonald, S. E., Keating, S., Ahmed, K. A., Armstrong, J. A., Ashworth, M., Asiimwe, I. G., Bakshi, S., Barlow, S. L., Booth, L., Brennan, B., Bullock, K., Catterall, B. W., Clark, J. J., Clarke, E. A., Cole, S., Cooper, L., Cox, H., Davis, C., Dincarslan, O., Dunn, C., Dyer, P., Elliott, A., Evans, A., Finch, L., Fisher, L. W., Foster, T., Garcia-Dorival, I., Gunning, P., Hartley, C., Jensen, R. L., Jones, C. B., Jones, T. R., Khandaker, S., King, K., Kiy, R. T., Koukorava, C., Lake, A., Lant, S., Latawiec, D., Lavelle-Langham, L., Lefteri, D., Lett, L., Livoti, L. A., Mancini, M., McDonald, S., McEvoy, L., McLauchlan, J., Metelmann, S., Miah, N. S., Middleton, J., Mitchell, J., Moore, S. C., Murphy, E. G., Penrice-Randal, R., Pilgrim, J., Prince, T., Reynolds, W., Ridley, P. M., Sales, D., Shaw, V. E., Shears, R. K., Small, B., Subramaniam, K. S., Szemiel, A., Taggart, A., Tanianis-Hughes, J., Thomas, J., Trochu, E., van Tonder, L., Wilcock, E., Zhang, J. E., Flaherty, L., Maziere, N., Cass, E., Carracedo, A. D., Carlucci, N., Holmes, A., Massey, H., Murphy, L., McCafferty, S., Clark, R., Fawkes, A., Morrice, K., Maclean, A., Wrobel, N., Donnelly, L., Coutts, A., Hafezi, K., MacGillivray, L., Gilchrist, T., Adeniji, K., Agranoff, D., Agwuh, K., Ail, D., Aldera, E. L., Alegria, A., Allen, S., Angus, B., Ashish, A., Atkinson, D., Bari, S., Barlow, G., Barnass, S., Barrett, N., Bassford, C., Basude, S., Baxter, D., Beadsworth, M., Bernatoniene, J., Berridge, J., Berry, C., Best, N., Bothma, P., Chadwick, D., Brittain-Long, R., Bulteel, N., Burden, T., Burtenshaw, A., Caruth, V., Chadwick, D., Chambler, D., Chee, N., Child, J., Chukkambotla, S., Clark, T., Collini, P., Cosgrove, C., Cupitt, J., Cutino-Moguel, M.-T., Dark, P., Dawson, C., Dervisevic, S., Donnison, P., Douthwaite, S., Drummond, A., DuRand, I., Dushianthan, A., Dyer, T., Evans, C., Eziefula, C., Fegan, C., Finn, A., Fullerton, D., Garg, S., Garg, S., Garg, A., Gkrania-Klotsas, E., Godden, J., Goldsmith, A., Graham, C., Hardy, E., Hartshorn, S., Harvey, D., Havalda, P., Hawcutt, D. B., Hobrok, M., Hodgson, L., Hormis, A., Jacobs, M., Jain, S., Jennings, P., Kaliappan, A., Kasipandian, V., Kegg, S., Kelsey, M., Kendall, J., Kerrison, C., Kerslake, I., Koch, O., Koduri, G., Koshy, G., Laha, S., Laird, S., Larkin, S., Leiner, T., Lillie, P., Limb, J., Linnett, V., Little, J., Lyttle, M., MacMahon, M., MacNaughton, E., Mankregod, R., Masson, H., Matovu, E., McCullough, K., McEwen, R., Meda, M., Mills, G., Minton, J., Mirfenderesky, M., Mohandas, K., Mok, Q., Moon, J., Moore, E., Morgan, P., Morris, C., Mortimore, K., Moses, S., Mpenge, M., Mulla, R., Murphy, M., Nagel, M., Nagarajan, T., Nelson, M., Norris, L., O’Shea, M. K., Otahal, I., Ostermann, M., Pais, M., Palmieri, C., Panchatsharam, S., Papakonstantinou, D., Paraiso, H., Patel, B., Pattison, N., Pepperell, J., Peters, M., Phull, M., Pintus, S., Pooni, J. S., Planche, T., Post, F., Price, D., Prout, R., Rae, N., Reschreiter, H., Reynolds, T., Richardson, N., Roberts, M., Roberts, D., Rose, A., Rousseau, G., Ruge, B., Ryan, B., Saluja, T., Schmid, M. L., Shah, A., Shanmuga, P., Sharma, A., Shawcross, A., Sizer, J., Shankar-Hari, M., Smith, R., Snelson, C., Spittle, N., Staines, N., Stambach, T., Stewart, R., Subudhi, P., Szakmany, T., Tatham, K., Thomas, J., Thompson, C., Thompson, R., Tridente, A., Tupper-Carey, D., Twagira, M., Vallotton, N., Vancheeswaran, R., Vincent-Smith, L., Visuvanathan, S., Vuylsteke, A., Waddy, S., Wake, R., Walden, A., Welters, I., Whitehouse, T., Whittaker, P., Whittington, A., Papineni, P., Wijesinghe, M., Williams, M., Wilson, L., Cole, S., Winchester, S., Wiselka, M., Wolverson, A., Wootton, D. G., Workman, A., Yates, B., Young, P., Paterson, N. G., Williams, M. A., Hall, D. R., Fry, E. E., Mongkolsapaya, J., Ren, J., Schreiber, G., Stuart, D. I., & Screaton, G. R.
Affiliations
  • Centre for Human Genetics (GB)
  • Weizmann Institute of Science (IL)
  • Diamond Light Source (GB)
  • University of Oxford (GB)
  • Medawar Building for Pathogen Research (GB)
  • Oxford University Hospitals NHS Trust (GB)
  • University of Leicester (GB)
  • University Hospitals of Leicester NHS Trust (GB)
  • Fiocruz Amazônia (BR)
  • Fundação Oswaldo Cruz (BR)
  • South African Medical Research Council (ZA)
  • Public Health England (GB)
  • John Radcliffe Hospital (GB)
  • Chang Gung University (TW)
  • Siriraj Hospital (TH)
  • Roslin Institute (GB)
  • University of Liverpool (GB)
  • Imperial College London (GB)
Corresponding author
  • Mongkolsapaya, Juthathip
  • Ren, Jingshan
  • Schreiber, Gideon
  • Screaton, Gavin R.
ORCID
Venue
Cell
Publisher
Elsevier BV
Published
2022-02
Volume
185
Issue
3
Pages
467-484.e15
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2021.12.046
PMC
PMC8723827
OpenAlex
W4206153788
Cited by
930
References
73
Citations by year
2026: 30 · 2025: 73 · 2024: 121 · 2023: 246 · 2022: 455
FWCI
109.39
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Edinburgh Research Explorer (University of Edinburgh) (publishedVersion, cc-by)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion, other-oa)
  • White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
  • HAL (submittedVersion)
  • Arca - Repositório Institucional da Fiocruz (submittedVersion, other-oa)
  • Figshare (submittedVersion, cc-by)
  • Research Explorer (The University of Manchester) (submittedVersion, cc-by)
  • University of Birmingham Research Portal (University of Birmingham) (submittedVersion, other-oa)
  • Spiral (Imperial College London) (submittedVersion, other-oa)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
  • Apollo (cc-by)
Funders
  • Israel Science Foundation (3814/19)
  • National Institute for Health Research (63/125,984, 277,546, PCT/GB2012/000467)
  • MRC (MC_PC_19059)
  • Fundação Oswaldo Cruz (VPPCB-007- FIO-18-2-30)
  • NIHR Oxford Biomedical Research Centre
  • Department of Health and Social Care
  • Wellcome Trust (203141/Z/16/Z, 101122/Z/13/Z, 090532/Z/09/Z)
  • Bill &amp; Melinda Gates Foundation (INV-016202)
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico (403276/2020-9)
  • National Institutes of Health (U19 I082360)
  • Oak Foundation
  • Coalition for Epidemic Preparedness Innovations
  • Chinese Academy of Medical Sciences
  • Public Health England
  • UK Research and Innovation
  • CAMS (2018-I2M-2-002)
  • Fundação de Amparo à Pesquisa do Estado do Amazonas
Topics
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
  • Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
Keywords
Omicron variant, spike protein mutations, neutralizing antibodies, immune evasion, vaccine escape, monoclonal antibodies, ACE2 binding site, receptor binding affinity, SARS-CoV-2 variants, COVID-19 pandemic

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