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Cited by 728SARS-CoV-2 and COVID-19 ResearchAnimal Virus Infections Studiesvaccines and immunoinformatics approaches

Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies

Open access
Collier, Dami A., De Marco, Anna, Ferreira, Isabella A. T. M., Meng, Bo, Datir, Rawlings P., Walls, Alexandra C., Kemp, Steven A., Bassi, Jessica +1137 more·2021·Nature
DOI 10.1038/s41586-021-03412-7PMC PMC7616976

Published version of a preprint

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Abstract

Transmission of SARS-CoV-2 is uncontrolled in many parts of the world; control is compounded in some areas by the higher transmission potential of the B.1.1.7 variant 1, which has now been reported in 94 countries. It is unclear whether the response of the virus to vaccines against SARS-CoV-2 on the basis of the prototypic strain will be affected by the mutations found in B.1.1.7. Here we assess the immune responses of individuals after vaccination with the mRNA-based vaccine BNT162b2 2. We measured neutralizing antibody responses after the first and second immunizations using pseudoviruses that expressed the wild-type spike protein or a mutated spike protein that contained the eight amino acid changes found in the B.1.1.7 variant. The sera from individuals who received the vaccine exhibited a broad range of neutralizing titres against the wild-type pseudoviruses that were modestly reduced against the B.1.1.7 variant. This reduction was also evident in sera from some patients who had recovered from COVID-19. Decreased neutralization of the B.1.1.7 variant was also observed for monoclonal antibodies that target the N-terminal domain (9 out of 10) and the receptor-binding motif (5 out of 31), but not for monoclonal antibodies that recognize the receptor-binding domain that bind outside the receptor-binding motif. Introduction of the mutation that encodes the E484K substitution in the B.1.1.7 background to reflect a newly emerged variant of concern (VOC 202102/02) led to a more-substantial loss of neutralizing activity by vaccine-elicited antibodies and monoclonal antibodies (19 out of 31) compared with the loss of neutralizing activity conferred by the mutations in B.1.1.7 alone. The emergence of the E484K substitution in a B.1.1.7 background represents a threat to the efficacy of the BNT162b2 vaccine.

AI snapshot

Written from the paper’s full text.

TL;DR

In recipients of the BNT162b2 mRNA vaccine, B.1.1.7 spike mutations modestly reduced neutralization by vaccine-elicited and convalescent sera, while adding E484K caused a larger loss of neutralization. B.1.1.7 also escaped many NTD-specific and some RBM-specific monoclonal antibodies, and its RBD bound human ACE2 with higher affinity than wild type.

Key findings

  • Among 29 vaccinees with wild-type neutralization after a single BNT162b2 dose, 20 showed reduced neutralization against B.1.1.7; mean fold change was approximately 3.2 (SD 5.7) after the first dose and 1.9 (SD 0.9) after the second dose, while wild-type GMT rose from 77 to 318.
  • Convalescent sera from 27 recovered individuals had a wild-type GMT of 1334 and a B.1.1.7 fold change of 4.5; adding E484K to B.1.1.7 increased the mean fold change to 6.7 after second-dose vaccine sera and 11.4 for convalescent sera.
  • Of 60 monoclonal antibodies from 15 recovered individuals, 20/60 (33.3%) showed >2-fold loss of B.1.1.7 neutralization; 8/10 NTD-targeting mAbs fully escaped and 1 additional partially escaped, while 5/31 RBM-targeting mAbs had >100-fold decrease and 6 more had 2-to-10-fold reduction; non-RBM RBD mAbs retained activity.
  • B.1.1.7 RBD bound human ACE2 with an affinity of 22 nM versus 133 nM for wild-type RBD; the K417N/E484K/N501Y triple mutant RBD bound ACE2 at 64 nM.

Methods

  • Serum and PBMC samples were collected from 37 participants three weeks after the first BNT162b2 dose; median age was 63.5 years (IQR 47–84) and 33% were female. Convalescent sera from 27 recovered individuals and 60 mAbs from 15 donors were also tested.
  • Neutralization was measured with lentiviral or MLV pseudoviruses expressing wild-type/D614G spike or B.1.1.7 spike mutations, with or without E484K/K417N, using ACE2/TMPRSS2-expressing target cells and luciferase readout; ID50/IC50 values were summarized as geometric mean titres.
  • Binding and affinity were assessed by biolayer interferometry for mAbs to WT, N501Y, or E484K RBD and for human ACE2 to WT, B.1.1.7, or triple-mutant RBD; statistical comparisons used Wilcoxon signed-rank tests, two-tailed t-tests, and Pearson correlation.

Limitations

  • The paper states the study was limited by modest sample size and notes that pseudotyping may not capture determinants outside spike that influence antibody escape in live replication-competent virus; live virus systems also require rigorous sequencing because mutations can arise during replication.
  • Evident from the text: the study measures in vitro neutralization and binding, not clinical vaccine efficacy or protection endpoints, so the implications for vaccine effectiveness are inferential.
  • Evident from the text: the vaccinated participants were older adults (median 63.5 years), which may limit generalizability to other age groups.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1038/s41586-021-03412-7

Cites

Statistics

Nothing to recompute.

Claims the paper makes

0 of 54 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Introduction of the E484K mutation in a B.1.1.7 background led to a more substantial loss of neutralising activity by vaccine-elicited antibodies and mAbs (19 out of 31) over that conferred by the B.1.1.7 mutations alone.

    “Introduction of the E484K mutation in a B.1.1.7 background to reflect newly emerging viruses in the UK led to a more substantial loss of neutralising activity by vaccine-elicited antibodies and mAbs (19 out of 31) over that conferred by the B.1.1.7 mutations alone.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The antibody responses measured in the 37 vaccinated participants are representative of BNT162b2 vaccine-elicited responses in the wider vaccinated population.
  • Findingown data

    The reduction in neutralisation against B.1.1.7 was also evident in sera from some convalescent patients.

    “This reduction was also evident in sera from some convalescent patients.”
    Quote in the paperNot a substantial claim
  • Findingown data

    The antibody response was heterogeneous with almost 100-fold variation in IgG titres to S and RBD across the vaccinated participants.

    “However, the antibody response was heterogeneous with almost 100-fold variation in IgG titres to S and RBD across the vaccinated participants.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The antibody responses measured in the 37 vaccinated participants are representative of BNT162b2 vaccine-elicited responses in the wider vaccinated population.
  • Findingown data

    Convalescent sera showed additional loss of activity against the mutant B.1.1.7 spike with E484K, with fold change of 11.4 relative to WT.

    “Similarly when we tested a panel of convalescent sera with a range of neutralisation titres (Fig. 1f-g), we observed additional loss of activity against the mutant B.1.1.7 spike with E484K, with fold change of 11.4 relative to WT (Fig. 3f-g).”
    Quote in the paperSubstantial claim
  • Findingown data

    Following the second dose, a significant loss of neutralising activity was observed for the pseudovirus with B.1.1.7 spike mutations and E484K.

    “Following second dose, we observed a significant loss of neutralising activity for the pseudovirus with B.1.1.7 spike mutations and E484K (Fig 3d-e).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The antibody responses measured in the 37 vaccinated participants are representative of BNT162b2 vaccine-elicited responses in the wider vaccinated population.
  • May combine two claims. 38
  • Classified as probably not a substantial claim. 21

  • May combine two claims.

    Findingown data

    Vaccine sera exhibited a broad range of neutralising titres against wild-type pseudoviruses that were modestly reduced against the B.1.1.7 variant.

    “The vaccine sera exhibited a broad range of neutralising titres against the wild-type pseudoviruses that were modestly reduced against B.1.1.7 variant.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The antibody responses measured in the 37 vaccinated participants are representative of BNT162b2 vaccine-elicited responses in the wider vaccinated population.

  • May combine two claims.

    Findingown data

    S and RBD antibody titres in vaccinated participants were much higher than in healthy controls, but lower than in individuals recovered from COVID-19 and therapeutic convalescent plasma.

    “These data showed S and RBD antibody titres much higher than in healthy controls, but lower than in individuals recovered from COVID-19 and titres observed in therapeutic convalescent plasma.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The antibody responses measured in the 37 vaccinated participants are representative of BNT162b2 vaccine-elicited responses in the wider vaccinated population.

  • May combine two claims.

    Findingown data

    Decreased B.1.1.7 neutralisation was observed with monoclonal antibodies targeting the N-terminal domain (9 out of 10) and the Receptor Binding Motif (5 out of 31), but not in neutralising mAbs binding outside the RBM.

    “Decreased B.1.1.7 neutralisation was also observed with monoclonal antibodies targeting the N-terminal domain (9 out of 10), the Receptor Binding Motif (RBM) (5 out of 31), but not in neutralising mAbs binding outside the RBM.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Out of the 19 RBM-specific mAbs that showed reduced or loss of neutralization of the TM mutant, 16 showed complete or partial loss of binding to the E484K RBD mutant, consistent with E484K being an important viral escape mutation.

    “Out of the 19 RBM-specific mAbs that showed reduced or loss of neutralization of TM mutant (Fig. 4d), 16 showed a complete or partial loss of binding to E484K RBD mutant (Fig. 4g-h), consistent with findings that E484K is an important viral escape mutation26, 39, 27.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [26] Gregson, J. et al. Human immunodeficiency virus-1 viral load is elevated in individuals with reverse-transcriptase mutation M184V/I during virological failure of first-line antiretroviral therapy and is associated with compensatory mutation L74I. J. Infect. Dis. 222, 1108–1116 (2019). source

      Not checked in the free run.

    • cites [39] Shu, Y. & McCauley, J. GISAID: global initiative on sharing all influenza data — from vision to reality. Euro Surveill. 22, 30494 (2017). source

      Not checked in the free run.

    • cites [27] Forloni, M., Liu, A. Y. & Wajapeyee, N. Creating insertions or deletions using overlap extension polymerase chain reaction (PCR) mutagenesis. Cold Spring Harb. Protoc. https://doi.org/10.1101/pdb.prot097758 (2018). source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    The B.1.1.7 mutant virus fully escaped neutralization by 8 out of 10 NTD-targeting mAbs (80%), and partially escaped from an additional mAb (10%).

    “Remarkably, the B.1.1.7 mutant virus was found to fully escape neutralization by 8 out of 10 NTD-targeting mAbs (80%), and partial escape from an additional mAb (10%) (Fig. 4c).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The mean fold change for the E484K B.1.1.7 Spike was 6.7 compared to 1.9 for B.1.1.7, relative to WT.

    “The mean fold change for the E484K B.1.1.7 Spike was 6.7 compared to 1.9 for B.1.1.7, relative to WT (Fig. 3a-c).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The antibody responses measured in the 37 vaccinated participants are representative of BNT162b2 vaccine-elicited responses in the wider vaccinated population.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    The number of B.1.1.7 sequences has been increasing since the start of December 2020.

    “The number of B.1.1.7 sequences has been increasing since the start of December 2020 (Fig. 2c).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    3 of the 19 mAbs that lost neutralization of the TM mutant (S2D8, S2H7 and S2X128) were previously shown to lose binding and neutralization to the K417V mutant, and here shown to be sensitive to either N501Y or E484K mutations.

    “Similarly, 3 of the 19 mAbs that lost neutralization of TM mutant (S2D8, S2H7 and S2X128) were previously shown to lose binding and neutralization to the K417V mutant, and here shown to be sensitive to either N501Y or E484K mutations.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Findingnone given

    Substitutions at K417 have been found in 5 sequences from recent viral isolates within the B.1.1.7 lineage (K417 to N, E or R).

    “The inclusion of the K417N substitution was prompted by the observation that substitutions at this position have been found in 5 sequences from recent viral isolates within the B.1.1.7 lineage (K417 to N, E or R).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    A pseudovirus bearing the full set of mutations present in the B.1.1.7 variant resulted in a small reduction in neutralisation by sera from vaccinees that was more marked following the first dose than the second dose.

    “However, we demonstrated that a pseudovirus bearing S protein with the full set of mutations present in the B.1.1.7 variant (i.e., ΔH69/V70, Δ144, N501Y, A570D, P681H, T716I, S982A, D1118H) did result in small reduction in neutralisation by sera from vaccinees that was more marked following the first dose than the second dose.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The antibody responses measured in the 37 vaccinated participants are representative of BNT162b2 vaccine-elicited responses in the wider vaccinated population.

  • May combine two claims.

    Findingown data

    Three of these 16 mAbs also lost binding to an RBD carrying N501Y, indicating that a fraction of RBM antibodies are sensitive to both N501Y and E484K mutations.

    “Three of these 16 mAbs also lost binding to an RBD carrying N501Y, indicating that a fraction of RBM antibodies are sensitive to both N501Y and E484K mutations.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    ACE2 bound with comparable on-rates to both RBDs, but the observed dissociation rate constant was slower for B.1.1.7 than for the WT RBD.

    “Although ACE2 bound with comparable on-rates to both RBDs, the observed dissociation rate constant was slower for B.1.1.7 than for the WT RBD (Table 1).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Amongst sera from 27 recovered individuals, the GMT at 50% neutralisation was 1334 for WT, significantly higher than post second dose vaccination.

    “Amongst sera from 27 recovered individuals, the GMT at 50% neutralisation was 1334 for WT, significantly higher than post second dose vaccination (Fig. 1f-g).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Phylogenetic analysis suggests multiple independent acquisitions of E484K, with one lineage appearing to expand over time, indicating active transmission.

    “Phylogenetic analysis suggests that there have been multiple independent acquisitions, with one lineage appearing to expand over time, indicating active transmission (Fig. 2b).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Following the second dose, GMT was markedly increased compared with first dose titres, and the mean fold change had reduced to 1.9 (SD 0.9).

    “Following the second dose, GMT was markedly increased compared with first dose titres, and the mean fold change had reduced to 1.9 (SD 0.9) (Fig. 1d-e).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The antibody responses measured in the 37 vaccinated participants are representative of BNT162b2 vaccine-elicited responses in the wider vaccinated population.

  • May combine two claims.

    Findingown data

    Out of the 60 mAbs tested, 20 (33.3%) showed >10 fold loss of neutralising activity of the TM mutant compared to WT SARS-CoV-2, and of these 19 are RBM-specific mAbs.

    “Out of the 60 mAbs tested, 20 (33.3%) showed >10 fold loss of neutralising activity of TM mutant compared to WT SARS-CoV-2 (Fig. 4 a-b and Extended Data Fig. 5), and of these 19 are RBM-specific mAbs.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The ACE2 binding affinity of 64 nM for the TM RBD is driven by a faster off-rate than observed for the B.1.1.7 RBD but slower than for the WT RBD.

    “We determined an ACE2 binding affinity of 64 nM for the TM RBD which is driven by a faster off-rate than observed for the B.1.1.7 RBD but slower than for the WT RBD.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    A broad range of T cell responses was measured by IFN gamma FluoroSpot against SARS-CoV-2 peptides in vaccinees.

    “A broad range of T cell responses was measured by IFN gamma FluoroSpot against SARS-CoV-2 peptides in vaccinees.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The antibody responses measured in the 37 vaccinated participants are representative of BNT162b2 vaccine-elicited responses in the wider vaccinated population.

  • May combine two claims.

    Findingown data

    Of the 31 RBM-targeting mAbs, 5 (16.1%) showed more than 100-fold decrease in B.1.1.7 neutralization, and an additional 6 mAbs (19.4%) had a partial 2-to-10-fold reduction.

    “Of the 31 RBM-targeting mAbs, 5 (16.1%) showed more than 100-fold decrease in B.1.1.7 neutralization, and additional 6 mAbs (19.4%) had a partial 2-to-10-fold reduction (Fig. 4d).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The 5 RBM-specific mAbs that failed to neutralize B.1.1.7 showed complete loss of binding to N501Y RBD mutant, demonstrating a role for N501Y as an escape mechanism for certain RBM-targeting mAbs.

    “The 5 RBM-specific mAbs that failed to neutralize B.1.1.7 variant (Fig. 4d) showed a complete loss of binding to N501Y RBD mutant (Fig. 4g-h), demonstrating a role for this mutation as an escape mechanism for certain RBM-targeting mAbs.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Multiple B.1.1.7 sequences in the UK bear E484K, with early evidence of transmission as well as independent acquisitions.

    “Worryingly, we have shown that there are multiple B.1.1.7 sequences in the UK bearing E484K with early evidence of transmission as well as independent aquisitions.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Licensed SARS-CoV-2 vaccines target the spike protein and have protection rates ranging from 62 to 95%.

    “SARS-CoV-2 vaccines have recently been licensed that target the spike (S) protein, either using mRNA or adenovirus vector technology with protection rates ranging from 62 to 95%9–11.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [9] Andreano, E. et al. SARS-CoV-2 escape in vitro from a highly neutralizing COVID-19 convalescent plasma. Preprint at https://doi.org/10.1101/2020.12.28.424451 (2020). source

      Not checked in the free run.

    • cites [10] Kalyaanamoorthy, S., Minh, B. Q., Wong, T. K. F., von Haeseler, A. & Jermiin, L. S. ModelFinder: fast model selection for accurate phylogenetic estimates. Nat. Methods 14, 587–589 (2017). source

      Not checked in the free run.

    • cites [11] Starr, T. N. et al. Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding. Cell 182, 1295–1310 (2020). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Neutralising GMT was below cut-off in most cases after prime dose, but titres substantially increased after boost immunization.

    “Neutralisating geometric mean titre (GMT) was below cut-off in most cases after prime dose, but as anticipated, titres substantially increased after boost immunization18.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [18] Wu, K. et al. mRNA-1273 vaccine induces neutralizing antibodies against spike mutants from global SARS-CoV-2 variants. Preprint at https://doi.org/10.1101/2021.01.25.427948 (2021). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The BNT162b2 vaccine encodes the full-length trimerised S protein of SARS-CoV-2 and is formulated in lipid nanoparticles.

    “The BNT162b2 vaccine encodes the full-length trimerised S protein of SARS CoV-2 and is formulated in lipid nanoparticles for delivery to cells12.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [12] Verschoor, C. P. et al. Microneutralization assay titres correlate with protection against seasonal influenza H1N1 and H3N2 in children. PLoS ONE 10, e0131531 (2015). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In clinical studies of BNT162b2, high levels of protection against infection and severe disease were observed after the second dose.

    “In clinical studies of the Pfizer-BioNTech BNT162b2 vaccine, high levels of protection against infection and severe disease were observed after the second dose10.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [10] Kalyaanamoorthy, S., Minh, B. Q., Wong, T. K. F., von Haeseler, A. & Jermiin, L. S. ModelFinder: fast model selection for accurate phylogenetic estimates. Nat. Methods 14, 587–589 (2017). source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Continued viral evolution led to the emergence and selection of SARS-CoV-2 variants with enhanced infectivity/transmissibility and ability to circumvent drug and immune control.

    “Continued viral evolution led to the emergence and selection of SARS-CoV-2 variants with enhanced infectivity/transmissibility2,3 4,5 and ability to circumvent drug6 and immune control7,8.”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites 2,3 4,5

      Not checked in the free run.

    • cites [6] Public Health England. PHE statement on Variant of Concern and new Variant Under Investigation. https://www.gov.uk/government/news/phe-statement-on-variant-of-concern-and-new-variant-under-investigation (2021).

      Not checked in the free run.

    • cites [7] Thomson, E. C. et al. Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity. Cell 184, 1171–1187 (2021). source

      Not checked in the free run.

    • cites [8] Greaney, A. J. et al. Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies. Cell Host Microbe https://doi.org/10.1016/j.chom.2021.02.003 (2021). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    In older adults mean GMT was only 12 in a preliminary analysis of 12 participants and increased to 109 after the second dose.

    “In older adults mean GMT was only 12 in a preliminary analysis of 12 participants19 and increased to 109 after the second dose.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [19] McCallum, M. et al. N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2. Preprint at https://doi.org/10.1101/2021.01.14.426475 (2021). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    NTD-specific mAbs were suggested to interfere with viral entry based on other accessory receptors, such as DC-SIGN and L-SIGN, and their neutralization potency was found to be dependent on different in vitro culture conditions.

    “NTD-specific mAbs were suggested to interfere with viral entry based on other accessory receptors, such as DC-SIGN and L-SIGN46, and their neutralization potency was found to be dependent on different in vitro culture conditions24.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [46]

      Not checked in the free run.

    • cites [24] Weisblum, Y. et al. Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants. eLife 9, e61312 (2020). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Neutralising antibody titres appeared highly correlated with vaccine protection against SARS-CoV-2 rechallenge in non-human primates, and there was no correlation between T cell responses and protection.

    “Neutralising antibody titres appeared to be highly correlated with vaccine protection against SARS-CoV-2 rechallenge in non-human primates, and importantly, there was no correlation between T cell responses (as measured by ELISpot) and protection38.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [38] Walls, A. C. et al. Elicitation of potent neutralizing antibody responses by designed protein nanoparticle vaccines for SARS-CoV-2. Cell 183, 1367–1382 (2020). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    SARS-CoV-2 and SARS-CoV enter host cells through binding of the S glycoprotein to angiotensin converting enzyme 2 (ACE2).

    “SARS-CoV-2 and SARS-CoV enter host cells through binding of the S glycoprotein to angiotensin converting enzyme 2 (ACE2)1,28.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [1] Volz, E. et al. Transmission of SARS-CoV-2 lineage B.1.1.7 in England: insights from linking epidemiological and genetic data. Preprint at https://doi.org/10.1101/2020.12.30.20249034 (2021). source

      Not checked in the free run.

    • cites [28] Case, J. B. et al. Neutralizing antibody and soluble ACE2 inhibition of a replication-competent VSV-SARS-CoV-2 and a clinical isolate of SARS-CoV-2. Cell Host Microbe 28, 475–485 (2020). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationown data

    The greater reduction in neutralisation after the first dose than after the second dose could be related to increased breadth, potency or concentration of antibodies following the boost dose.

    “This could be related to increased breadth/potency/concentration of antibodies following the boost dose.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Enhanced binding of the B.1.1.7 RBD to human ACE2 resulting from the N501Y mutation might participate in the efficient ongoing transmission of this newly emergent SARS-CoV-2 lineage, and possibly reduced opportunity for antibody binding.

    “Enhanced binding of the B.1.1.7 RBD to human ACE2 resulting from the N501Y mutation might participate in the efficient ongoing transmission of this newly emergent SARS-CoV-2 lineage, and possibly reduced opportunity for antibody binding.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Deletion of residue 144 abrogates binding by 4 out of 6 NTD-specific mAbs tested, possibly accounting for viral neutralization escape by most NTD-specific antibodies.

    “We previously showed that the deletion of residue 144 abrogates binding by 4 out of 6 NTD-specific mAbs tested, possibly accounting for viral neutralization escape by most NTD-specific antibodies24.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [24] Weisblum, Y. et al. Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants. eLife 9, e61312 (2020). source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The observation that 9 out of 10 NTD-specific neutralising antibodies failed to show a complete or near-complete loss of neutralising activity against B.1.1.7 indicates that this new variant may have evolved also to escape from this class of antibodies, which may have a yet unrecognized role in protective immunity.

    “The observation that 9 out of 10 NTD-specific neutralising antibodies failed to show a complete or near-complete loss of neutralising activity against B.1.1.7 indicates that this new variant may have evolved also to escape from this class of antibodies, that may have a yet unrecognized role in protective immunity.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Other studies reported small reduction of neutralization against the B.1.1.7 variant against sera from individuals vaccinated with two doses of BNT162b2 and mRNA-1273.

    “Other studies also reported small reduction of neutralization against the B.1.1.7 variant against sera from individuals vaccinated with two doses of BNT162b242 and mRNA-127343.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [42] Minh, B. Q., Nguyen, M. A. & von Haeseler, A. Ultrafast approximation for phylogenetic bootstrap. Mol. Biol. Evol. 30, 1188–1195 (2013). source

      Not checked in the free run.

    • cites [43]

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    K417N is slightly detrimental to ACE2 binding, explaining the intermediate affinity determined for the TM RBD compared to the B.1.1.7 and WT RBDs, likely by disrupting the salt bridge formed with ACE2 residue D30.

    “Based on our previous deep-mutational scanning measurements using dimeric ACE2, we propose that the K417N mutation is slightly detrimental to ACE2 binding explaining the intermediate affinity determined for the TM RBD compared to the B.1.17 and WT RBDs, likely as a result of disrupting the salt bridge formed with ACE2 residue D30.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Passive transfer of purified polyclonal IgGs from convalescent macaques protected naïve macaques against subsequent SARS-CoV-2 challenge.

    “Moreover, passive transfer of purified polyclonal IgGs from convalescent macaques protected naïve macaques against subsequent SARS-CoV-2 challenge39.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [39] Shu, Y. & McCauley, J. GISAID: global initiative on sharing all influenza data — from vision to reality. Euro Surveill. 22, 30494 (2017). source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    RBD antibodies against N501Y could play a role in decreased neutralisation by sera, with the overall impact possibly modulated by other mutations present in B.1.1.7 and by the relative dominance of NTD versus RBM antibodies in polyclonal sera.

    “RBD antibodies against N501Y could play a role in decreased neutralisation by sera, with the overall impact possibly modulated by other mutations present in B.1.1.7, as well as the relative dominance of NTD versus RBM antibodies in polyclonal sera.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    The decreased neutralising activity of immune sera from vaccinees and convalescent patients against B.1.1.7, but not against the Δ69/70-501Y-570D mutant, could result from loss of neutralising activity of both RBD- and NTD-targeting antibodies, and suggests that the key mutation is Δ144.

    “The decreased neutralising activity of the immune sera from vaccinees and convalescent patients against B.1.1.7, but not against Δ69/70-501Y-570D mutant (Fig. 1 and Extended Data Fig. 2), could be the result of a loss of neutralising activity of both RBD- and NTD-targeting antibodies, and suggests that the key mutation is Δ144.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    The contribution of N501Y to loss of neutralisation activity of polyclonal vaccine and convalescent sera is less clear, and interactions with other mutations are likely.

    “However, the contribution of N501Y to loss of neutralisation activity of polyclonal vaccine and convalescent sera is less clear, and interactions with other mutations likely.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The E484K substitution is antigenically important and has been reported as an escape mutation for several monoclonal antibodies including C121, C144, REGN10933 and Ly-CoV555.

    “The E484K substitution (Fig. 2a) is antigenically important, and has been reported as an escape mutation for several monoclonal antibodies including C121, C144, REGN10933 and Ly-CoV555 22.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [22] Tegally, H. et al. Detection of a SARS-CoV-2 variant of concern in South Africa. Nature https://doi.org/10.1038/s41586-021-03402-9 (2021). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In Wang et al., 6 out of 17 RBD-specific mAbs isolated from mRNA-1273 vaccinated individuals showed more than 100-fold neutralisation loss against N501Y mutant, consistent with the loss of neutralisation by 5 out of 29 RBM-specific mAbs described in this study.

    “In the study by Wang et al., 6 out 17 RDB-specific mAbs isolated from mRNA-1273 vaccinated individuals showed more than 100-fold neutralisation loss against N501Y mutant, a finding that is consistent with the loss of neutralisation by 5 out 29 RBM-specific mAbs described in this study.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [41] Minh, B. Q. et al. IQ-TREE 2: new models and efficient methods for phylogenetic inference in the genomic era. Mol. Biol. Evol. 37, 1530–1534 (2020). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Previous studies showed that the binding affinity of SARS-CoV for human ACE2 correlated with the rate of viral replication in distinct species, transmissibility and disease severity.

    “Previous studies showed that the binding affinity of SARS-CoV for human ACE2 correlated with the rate of viral replication in distinct species, transmissibility and disease severity 29–31.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [29] Naldini, L., Blömer, U., Gage, F. H., Trono, D. & Verma, I. M. Efficient transfer, integration, and sustained long-term expression of the transgene in adult rat brains injected with a lentiviral vector. Proc. Natl Acad. Sci. USA 93, 11382–11388 (1996). source

      Not checked in the free run.

    • cites [30] Gupta, R. K. et al. Full-length HIV-1 Gag determines protease inhibitor susceptibility within in-vitro assays. AIDS 24, 1651–1655 (2010). source

      Not checked in the free run.

    • cites [31] Kemp, S. A. et al. SARS-CoV-2 evolution during treatment of chronic infection. Nature https://doi.org/10.1038/s41586-021-03291-y (2021). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Limit of detection for 50% neutralization set at 10.

    “Limit of detection for 50% neutralization set at 10.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The Δ140 mutant subsequently acquired E484K, which resulted in a further 4-fold drop in neutralization titre, indicating that a two residue change across NTD and RBD represents an effective pathway of escape that can dramatically inhibit the polyclonal response.

    “This Δ140 mutant subsequently acquired E484K which resulted in a further 4-fold drop in neutralization titre indicating a two residue change across NTD and RBD represents an effective pathway of escape that can dramatically inhibit the polyclonal response.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [27] Forloni, M., Liu, A. Y. & Wajapeyee, N. Creating insertions or deletions using overlap extension polymerase chain reaction (PCR) mutagenesis. Cold Spring Harb. Protoc. https://doi.org/10.1101/pdb.prot097758 (2018). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Data are representative of 2 independent experiments.

    “Data are representative of 2 independent experiments.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Study design and conductnone given

    Although the spike pseudotyping system has been shown to faithfully represent full length infectious virus, there may be determinants outside S that influence escape from antibody neutralization either directly or indirectly in a live replication competent system.

    “Although the spike pseudotyping system has been shown to faithfully represent full length infectious virus, there may be determinants outside the S that influence escape from antibody neutralization either directly or indirectly in a live replication competent system.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Andreano et al. describe the emergence of Δ140 in virus co-incubated with potently neutralising convalescent plasma, causing a 4-fold reduction in neutralization titre.

    “Evidence for the importance role of NTD deletions in combination with E484K in immune escape is provided by Andreano et al.27 who describe the emergence of Δ140 in virus co-incubated with potently neutralising convalescent plasma, causing a 4-fold reduction in neutralization titre.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [27] Forloni, M., Liu, A. Y. & Wajapeyee, N. Creating insertions or deletions using overlap extension polymerase chain reaction (PCR) mutagenesis. Cold Spring Harb. Protoc. https://doi.org/10.1101/pdb.prot097758 (2018). source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The data suggest that vaccine escape to current Spike-directed vaccines designed against the Wuhan strain will be inevitable, particularly given that E484K is emerging independently and recurrently on a B.1.1.7 background and given the rapid global spread of B.1.1.7.

    “Our data suggest that vaccine escape to current Spike directed vaccines designed against the Wuhan strain will be inevitable, particularly given that E484K is emerging independently and recurrently on a B.1.1.7 (501Y.V1) background, and given the rapid global spread of B.1.1.7.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The antibody responses measured in the 37 vaccinated participants are representative of BNT162b2 vaccine-elicited responses in the wider vaccinated population.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The study was limited by modest sample size.

    “Our study was limited by modest sample size.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    An unstimulated and positive control mix was included in the FluoroSpot assay.

    “and an unstimulated and positive control mix (containing anti-CD3 (Mabtech AB),Staphylococcus Enterotoxin B (SEB), Phytohaemagglutinin (PHA) (all Sigma Aldrich))”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Interpretationnone given

    Where a curve is shifted to the right this indicates the virus is less sensitive to the neutralizing antibodies in the serum.

    “Where a curve is shifted to the right this indicates the virus is less sensitive to the neutralizing antibodies in the serum.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    An antibody of irrelevant specificity was included as negative control.

    “An antibody of irrelevant specificity was included as negative control.”
    Quote in the paperNot a substantial claim
53 of 53

  • The paper relies on this without support.

    The antibody responses measured in the 37 vaccinated participants are representative of BNT162b2 vaccine-elicited responses in the wider vaccinated population.

    “Thirty seven participants had received the first dose of BNT162b2 mRNA vaccine three weeks prior to blood draw for serum and peripheral blood monocnulear cells (PBMC) collection.”
    “The participants of this study were older adults, in line with the targeting of this age group in the initial rollout of the vaccination campaign in the UK.”
1 of 1

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Emergence of SARS-CoV-2 variants including Alpha, Beta, and Delta raised concerns about increased transmission and potential evasion from vaccine-induced immunity.

    “The emergence of several SARS-CoV-2 variants, including B.1.1.7 (Alpha), B.1.351 (Beta), and B.1.617.2 (Delta), has also raised concerns about increased transmission and potential evasion from vaccine-induced immunity (30–33).”

    From mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern (2021) · cites this paper as [30]

  • These results are generally aligned with in vitro neutralization assays showing a large reduction in neutralization against B.1.351 and little to no reduction against B.1.1.7 in fully vaccinated individuals.

    “These results are generally aligned with those from in vitro neutralization assays that have shown a large reduction in neutralization against B.1.351,and little to no reduction against B.1.1.7 in fully vaccinated individuals [7][8][9][10][11]17 .”

    From Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2-mRNA-vaccinated individuals (2021) · cites this paper as [9]

  • Breakthrough cases observed might be due to immune evasion mediated by particular alterations present in these strains.

    “From a biological point of view, the breakthrough cases observed in this study might be due to immune evasion, mediated by particular alterations present in these strains 9,[23][24][25][26][27] .”

    From Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2-mRNA-vaccinated individuals (2021) · cites this paper as [9]

  • A clinically accredited assay for N antibodies showed evidence that five individuals in each group had previously been infected with SARS-CoV-2, and this was adjusted for in multivariable analyses.

    “A clinically accredited assay for N antibodies 9 showed evidence that five individuals in each group had previously been infected with SARS-CoV-2 (Extended Data Table 1), and we adjusted for this in multivariable analyses (Extended Data Tables 2, 3).”

    From Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2 (2021) · cites this paper as [9]

  • The emergence of new variants with increased transmissibility and reduced sensitivity to vaccine-elicited antibodies, and for which vaccines are less able to prevent infection, has raised fears for vulnerable groups in whom the magnitude and quality of immune responses may be suboptimal.

    “In addition, the emergence of new variants with increased transmissibility 8 and reduced sensitivity to vaccine-elicited antibodies 9 , and for which vaccines are less able to prevent infection 10 , has raised fears for vulnerable groups in whom the magnitude and quality of immune responses may be suboptimal.”

    From Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2 (2021) · cites this paper as [9]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Second-dose titre increase is not an order of magnitude

    Major

    The reported titres give a 318/77 = 4.13-fold increase, not the approximately tenfold increase described.

    Reported 10 · recomputed 4.12987

  • Discussion reverses the NTD-antibody escape result

    Major

    The results say B.1.1.7 fully escaped eight of ten NTD-targeting antibodies and partially escaped another. The discussion instead says nine of ten failed to show complete or near-complete loss of activity.

  • RBM-antibody denominator changes from 31 to 29

    Minor

    The results describe five affected RBM-targeting antibodies out of 31, while the discussion describes the same study finding as five out of 29.

3 of 3

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References 65 · Cited by 728

Authors
Collier, D. A., De Marco, A., Ferreira, I. A. T. M., Meng, B., Datir, R. P., Walls, A. C., Kemp, S. A., Bassi, J., Pinto, D., Silacci-Fregni, C., Bianchi, S., Tortorici, M. A., Bowen, J., Culap, K., Jaconi, S., Cameroni, E., Snell, G., Pizzuto, M. S., Pellanda, A. F., Garzoni, C., Riva, A., The CITIID-NIHR BioResource COVID-19 Collaboration, Principal investigators, Baker, S., Dougan, G., Hess, C., Kingston, N., Lehner, P. J., Lyons, P. A., Matheson, N. J., Owehand, W. H., Saunders, C., Summers, C., Thaventhiran, J. E. D., Toshner, M., Weekes, M. P., nurses, C. &. V. R., Bucke, A., Calder, J., Canna, L., Domingo, J., Elmer, A., Fuller, S., Harris, J., Hewitt, S., Kennet, J., Jose, S., Kourampa, J., Meadows, A., O’Brien, C., Price, J., Publico, C., Rastall, R., Ribeiro, C., Rowlands, J., Ruffolo, V., Tordesillas, H., logistics, S., Bullman, B., Dunmore, B. J., Fawke, S., Gräf, S., Hodgson, J., Huang, C., Hunter, K., Jones, E., Legchenko, E., Matara, C., Martin, J., Mescia, F., O’Donnell, C., Pointon, L., Pond, N., Shih, J., Sutcliffe, R., Tilly, T., Treacy, C., Tong, Z., Wood, J., Wylot, M., acquisition, S. P. &. D., Bergamaschi, L., Betancourt, A., Bower, G., Cossetti, C., De Sa, A., Epping, M., Grenfell, R., Hinch, A., Huhn, O., Jackson, S., Jarvis, I., Lewis, D., Marsden, J., Nice, F., Okecha, G., Omarjee, O., Perera, M., Richoz, N., Romashova, V., Yarkoni, N. S., Sharma, R., Stefanucci, L., Stephens, J., Strezlecki, M., Turner, L., collection, C. D., De Bie, E. M. D. D., Bunclark, K., Josipovic, M., Mackay, M., Rossi, S., Selvan, M., Spencer, S., Yong, C., Royal Papworth Hospital, I. C. U., Ansaripour, A., Michael, A., Mwaura, L., Patterson, C., Polwarth, G., Addenbrooke’s Hospital, I. C. U., Polgarova, P., di Stefano, G., Cambridge & Peterborough Foundation Trust, Fahey, C., Michel, R., ANPC & Centre for Molecular Medicine & Innovative Therapeutics, Bong, S.-H., Coudert, J. D., Holmes, E., BioResource, N., Allison, J., Butcher, H., Caputo, D., Clapham-Riley, D., Dewhurst, E., Furlong, A., Graves, B., Gray, J., Ivers, T., Kasanicki, M., Le Gresley, E., Linger, R., Meloy, S., Muldoon, F., Ovington, N., Papadia, S., Phelan, I., Stark, H., Stirrups, K. E., Townsend, P., Walker, N., Webster, J., Elmer, A., Kingston, N., Graves, B., McCoy, L. E., Smith, K. G. C., Bradley, J. R., Temperton, N., Ceron-Gutierrez, L., Barcenas-Morales, G., The COVID-19 Genomics UK (COG-UK) Consortium, Funding acquisition, L. &. S., Robson, S. C., Funding acquisition, L. &. S., Loman, N. J., Connor, T. R., Leadership & supervision, M. C., Golubchik, T., Funding acquisition, M. C., Martinez Nunez, R. T., Funding acquisition, L. &. S., Ludden, C., Funding acquisition, L. &. 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L., Karamani, A., Ensell, L., Chatterton, W., Pusok, M., Dadrah, A., Symmonds, A., Sluga, G., Molnar, Z., Baker, P., Bonner, S., Essex, S., Barton, E., Padgett, D., Scott, G., Greenaway, J., Payne, B. A. I., Burton-Fanning, S., Waugh, S., Raviprakash, V., Sheriff, N., Blakey, V., Williams, L.-A., Moore, J., Stonehouse, S., Smith, L., Davidson, R. K., Bedford, L., Coupland, L., Wright, V., Chappell, J. G., Tsoleridis, T., Ball, J., Khakh, M., Fleming, V. M., Lister, M. M., Howson-Wells, H. C., Berry, L., Boswell, T., Joseph, A., Willingham, I., Duckworth, N., Walsh, S., Wise, E., Moore, N., Mori, M., Cortes, N., Kidd, S., Williams, R., Gifford, L., Bicknell, K., Wyllie, S., Lloyd, A., Impey, R., Malone, C. S., Cogger, B. J., Levene, N., Monaghan, L., Keeley, A. J., Partridge, D. G., Raza, M., Evans, C., Johnson, K., analysis, S. &., Betteridge, E., Farr, B. W., Goodwin, S., Quail, M. A., Scott, C., Shirley, L., Thurston, S. A. J., Rajan, D., Bronner, I. F., Aigrain, L., Redshaw, N. M., Lensing, S. V., McCarthy, S., Makunin, A., Balcazar, C. E., Gallagher, M. D., Williamson, K. A., Stanton, T. D., Michelsen, M. L., Warwick-Dugdale, J., Manley, R., Farbos, A., Harrison, J. W., Sambles, C. M., Studholme, D. J., Lackenby, A., Mbisa, T., Platt, S., Miah, S., Bibby, D., Manso, C., Hubb, J., Dabrera, G., Ramsay, M., Bradshaw, D., Schaefer, U., Groves, N., Gallagher, E., Lee, D., Williams, D., Ellaby, N., Hartman, H., Manesis, N., Patel, V., Ledesma, J., Twohig, K. A., Allara, E., Pearson, C., Cheng, J. K. J., Bridgewater, H. E., Frost, L. R., Taylor-Joyce, G., Brown, P. E., Tong, L., Broos, A., Mair, D., Nichols, J., Carmichael, S. N., Smollett, K. L., Nomikou, K., Aranday-Cortes, E., Johnson, N., Nickbakhsh, S., Vamos, E. E., Hughes, M., Rainbow, L., Eccles, R., Nelson, C., Whitehead, M., Gregory, R., Gemmell, M., Wierzbicki, C., Webster, H. J., Fisher, C. L., Signell, A. W., Betancor, G., Wilson, H. D., Nebbia, G., Flaviani, F., Cerda, A. C., Merrill, T. V., Wilson, R. E., Cotic, M., Bayzid, N., Thompson, T., Acheson, E., Rushton, S., O’Brien, S., Baker, D. J., Rudder, S., Aydin, A., Sang, F., Debebe, J., Francois, S., Vasylyeva, T. I., Zamudio, M. E., Gutierrez, B., Marchbank, A., Maksimovic, J., Spellman, K., McCluggage, K., Morgan, M., Beer, R., Afifi, S., Workman, T., Fuller, W., Bresner, C., Angyal, A., Green, L. R., Parsons, P. J., Tucker, R. M., Brown, R., Whiteley, M., tools, S. &. A., Bonfield, J., Puethe, C., Whitwham, A., Liddle, J., Rowe, W., Siveroni, I., Le-Viet, T., Gaskin, A., Visualization, Johnson, R., Wellcome Sanger Centre, Abnizova, I., Aigrain, L., Alderton, A., Ali, M., Allen, L., Amato, R., Anderson, R., Ariani, C., Austin-Guest, S., Bala, S., Barrett, J., Bassett, A., Battleday, K., Beal, J., Beale, M., Beaver, C., Bellany, S., Bellerby, T., Bellis, K., Berger, D., Berriman, M., Betteridge, E., Bevan, P., Binley, S., Bishop, J., Blackburn, K., Bonfield, J., Boughton, N., Bowker, S., Brendler-Spaeth, T., Bronner, I., Brooklyn, T., Buddenborg, S. K., Bush, R., Caetano, C., Cagan, A., Carter, N., Cartwright, J., Monteiro, T. C., Chapman, L., Chillingworth, T.-J., Clapham, P., Clark, R., Clarke, A., Clarke, C., Cole, D., Cook, E., Coppola, M., Cornell, L., Cornwell, C., Corton, C., Crackett, A., Cranage, A., Craven, H., Craw, S., Crawford, M., Cutts, T., Dabrowska, M., Davies, M., Davies, R., Dawson, J., Day, C., Densem, A., Dibling, T., Dockree, C., Dodd, D., Dogga, S., Dorman, M., Dougan, G., Dougherty, M., Dove, A., Drummond, L., Drury, E., Dudek, M., Durham, J., Durrant, L., Easthope, E., Eckert, S., Ellis, P., Farr, B., Fenton, M., Ferrero, M., Flack, N., Fordham, H., Forsythe, G., Foulser, L., Francis, M., Fraser, A., Freeman, A., Galvin, A., Garcia-Casado, M., Gedny, A., Girgis, S., Glover, J., Goncalves, S., Goodwin, S., Gould, O., Gourtovaia, M., Gray, A., Gray, E., Griffiths, C., Gu, Y., Guerin, F., Hamilton, W., Hanks, H., Harrison, E., Harrott, A., Harry, E., Harvison, J., Heath, P., Hernandez-Koutoucheva, A., Hobbs, R., Holland, D., Holmes, S., Hornett, G., Hough, N., Huckle, L., Hughes-Hallet, L., Hunter, A., Inglis, S., Iqbal, S., Jackson, A., Jackson, D., James, K., Jamrozy, D., Verdejo, C. 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F., Pardubska, B., Park, N., Parmar, A., Patel, G., Patel, M., Payne, M., Peacock, S., Petersen, A., Plowman, D., Preston, T., Prestwood, L., Puethe, C., Quail, M., Rajan, D., Rajatileka, S., Rance, R., Rawlings, S., Redshaw, N., Reynolds, J., Reynolds, M., Rice, S., Richardson, M., Roberts, C., Robinson, K., Robinson, M., Robinson, D., Rogers, H., Rojo, E. M., Roopra, D., Rose, M., Rudd, L., Sadri, R., Salmon, N., Saul, D., Schwach, F., Scott, C., Seekings, P., Shirley, L., Sillitoe, J., Simms, A., Sinnott, M., Sivadasan, S., Siwek, B., Sizer, D., Skeldon, K., Skelton, J., Slater-Tunstill, J., Sloper, L., Smerdon, N., Smith, C., Smith, C., Smith, J., Smith, K., Smith, M., Smith, S., Smith, T., Sneade, L., Soria, C. 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Affiliations
  • University of Cambridge (GB)
  • University of Washington (US)
  • Vir Biotechnology (Switzerland) (CH)
  • VIR Biotechnology (United States) (US)
  • Clinica Luganese Moncucco (CH)
  • University of Milan (IT)
  • University of Basel (CH)
  • Cambridge University Hospitals NHS Foundation Trust (GB)
  • University College London (GB)
  • University of Kent (GB)
  • Addenbrooke's Hospital (GB)
  • Papworth Hospital NHS Foundation Trust (GB)
  • Fulbourn Hospital (GB)
  • Murdoch University (AU)
  • King's College London (GB)
  • Public Health Wales (GB)
  • Wellcome Sanger Institute (GB)
  • University of Oxford (GB)
  • University of Brighton (GB)
  • Guy's Hospital (GB)
  • University Hospital Southampton NHS Foundation Trust (GB)
  • St Thomas' Hospital (GB)
  • Belfast Health and Social Care Trust (GB)
  • East Kent Hospitals University NHS Foundation Trust (GB)
  • University of Birmingham (GB)
  • Public Health England (GB)
  • University of Sheffield (GB)
  • University of Nottingham (GB)
  • Northumbria University (GB)
  • Queen's University Belfast (GB)
  • Quadram Institute (GB)
  • Public Health Scotland (GB)
  • Portsmouth Hospitals NHS Trust (GB)
  • University of Liverpool (GB)
  • Imperial College London (GB)
  • MRC University of Glasgow Centre for Virus Research (GB)
  • NHS Lothian (GB)
  • Newcastle upon Tyne Hospitals NHS Foundation Trust (GB)
  • University Hospitals Coventry and Warwickshire NHS Trust (GB)
  • University of East Anglia (GB)
  • University of Exeter (GB)
  • Brighton and Sussex University Hospitals NHS Trust (GB)
  • Betsi Cadwaladr University Health Board (GB)
  • Centre for Human Genetics (GB)
  • Cardiff and Vale University Health Board (GB)
  • Gloucestershire Hospitals NHS Foundation Trust (GB)
  • Sandwell & West Birmingham Hospitals NHS Trust (GB)
  • Norfolk and Norwich University Hospital (GB)
  • University of Warwick (GB)
  • Barking, Havering And Redbridge University Hospitals NHS Trust (GB)
  • Queen Elizabeth Hospital Birmingham (GB)
  • Wye Valley NHS Trust (GB)
  • University Hospitals of Leicester NHS Trust (GB)
  • Great Ormond Street Hospital (GB)
  • Royal Free London NHS Foundation Trust (GB)
  • South Tees Hospitals NHS Foundation Trust (GB)
  • North Cumbria Integrated Care NHS Foundation Trust (GB)
  • North Tees and Hartlepool NHS Foundation Trust (GB)
  • County Durham and Darlington NHS Foundation Trust (GB)
  • Basingstoke and North Hampshire Hospital (GB)
  • University of Portsmouth (GB)
  • Kettering General Hospital (GB)
  • North West London Pathology (GB)
  • University of Surrey (GB)
  • Swansea University (GB)
  • Royal Hampshire County Hospital (GB)
  • Wellcome/MRC Cambridge Stem Cell Institute (GB)
  • Royal Devon & Exeter NHS Foundation Trust (GB)
  • National Institute for Health and Care Research (GB)
  • NHS Greater Glasgow and Clyde (GB)
  • Leeds Teaching Hospitals NHS Trust (GB)
  • London School of Hygiene & Tropical Medicine (GB)
  • Maidstone and Tunbridge Wells NHS Trust (GB)
  • Norfolk County Council (GB)
  • East Suffolk and North Essex NHS Foundation Trust (GB)
  • Queen's Medical Centre (GB)
  • Manchester University NHS Foundation Trust (GB)
  • Princess Alexandra Hospital NHS Trust (GB)
  • Sheffield Teaching Hospitals NHS Foundation Trust (GB)
  • University of Edinburgh (GB)
  • Guy's and St Thomas' NHS Foundation Trust (GB)
  • University of Glasgow (GB)
Corresponding author
  • Corti, Davide
  • Gupta, Ravindra K.
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2021-03-11
Volume
593
Issue
7857
Pages
136-141
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/s41586-021-03412-7
PMC
PMC7616976
OpenAlex
W3134446480
Cited by
728
References
65
Citations by year
2026: 8 · 2025: 15 · 2024: 40 · 2023: 61 · 2022: 254 · 2021: 346 · 2020: 4
FWCI
55.51
Type
journal article
Language
en
Update notices
correction (2022-07-21)
Open access
Licence
Locations
  • Nature (publishedVersion)
  • medRxiv (acceptedVersion, cc-by-nc-nd)
  • Research Square (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
  • University of Birmingham Research Portal (University of Birmingham) (publishedVersion, other-oa)
  • ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion, cc-by-sa)
  • Northumbria Research Link (Northumbria University) (acceptedVersion)
  • UEA Digital Repository (University of East Anglia) (acceptedVersion)
  • PubMed Central (acceptedVersion, cc-by)
  • Kent Academic Repository (University of Kent) (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • Figshare (submittedVersion, cc-by)
  • PubMed Central (submittedVersion, cc-by-nc-nd)
  • RePEc: Research Papers in Economics (submittedVersion)
  • ePrints Soton (University of Southampton) (submittedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (submittedVersion)
  • Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
  • Apollo (University of Cambridge) (submittedVersion)
  • Apollo
Funders
  • Burroughs Wellcome Fund
  • Bill and Melinda Gates Foundation (OPP 1175094)
  • University of Portsmouth
  • Fordham University
  • Northumbria University
  • Wellcome Trust (R01GM120553, 200871, 108082/A/15/Z, 200871/Z/16/Z, 108082, 204911/Z/16/Z, HHSN272201700059C, WT108082AIA, DEL-15-006, DP1AI158186)
  • University Hospital Southampton NHS Foundation Trust
  • King's College Hospital NHS Foundation Trust
  • Public Health Wales
  • Fast Grants
  • Vir Biotechnology
  • Cancer Research UK (23923)
  • National Institute for Health and Care Research (NF-SI-0514-10109, NIHR301445, OPP1175094, ACF-2018-04-014)
  • Department of Health and Social Care (HHSN272201700059C)
  • Academy of Medical Sciences (AMS-CSF4-Torok, SBF004/1052)
  • University of Cambridge
  • University of East Anglia
  • University of Exeter
  • University of Southampton
  • University of Warwick
  • King's College London
  • University College London
  • University of Oxford
  • University of Birmingham
  • Queen's University Belfast
  • Swansea University
  • Public Health Agency
  • Public Health England
  • Cambridge University Hospitals (BRC 2017-22)
  • Queen's University
  • Oxford University Hospitals NHS Foundation Trust
  • Quadram Institute Bioscience
  • University Hospitals Coventry and Warwickshire NHS Trust
  • National Institutes of Health (1s10od023476-01)
  • Directorate for Biological Sciences
  • NIHR BioResource
  • Medical Research Council (MR/P008801/1, 200871/Z/16/Z, MR/R008698/1, MR/S00081X/1, MC_UP_1201/16)
  • Warwick Medical School
  • NIHR Cambridge Biomedical Research Centre
  • National Institute of General Medical Sciences (R01GM120553)
  • National Institute of Allergy and Infectious Diseases (HHSN272201700059C, DP1AI158186)
Topics
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
Keywords
SARS-CoV-2, B.1.1.7 variant, Omicron variant, BNT162b2, mRNA vaccines, neutralizing antibodies, vaccine escape, spike protein mutations, monoclonal antibodies, receptor-binding motif, N-terminal domain, COVID-19 vaccine efficacy

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