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Cited by 583SARS-CoV-2 and COVID-19 Researchvaccines and immunoinformatics approachesAnimal Virus Infections Studies

Antibody evasion by the P.1 strain of SARS-CoV-2

Open access
Dejnirattisai, Wanwisa, Zhou, Daming, Supasa, Piyada, Liu, Chang, Mentzer, Alexander J., Ginn, Helen M., Zhao, Yuguang, Duyvesteyn, Helen M.E. +42 more·2021·Cell
DOI 10.1016/j.cell.2021.03.055PMC PMC8008340

Published version of a preprint

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Abstract

Terminating the SARS-CoV-2 pandemic relies upon pan-global vaccination. Current vaccines elicit neutralizing antibody responses to the virus spike derived from early isolates. However, new strains have emerged with multiple mutations, including P.1 from Brazil, B.1.351 from South Africa, and B.1.1.7 from the UK (12, 10, and 9 changes in the spike, respectively). All have mutations in the ACE2 binding site, with P.1 and B.1.351 having a virtually identical triplet (E484K, K417N/T, and N501Y), which we show confer similar increased affinity for ACE2. We show that, surprisingly, P.1 is significantly less resistant to naturally acquired or vaccine-induced antibody responses than B.1.351, suggesting that changes outside the receptor-binding domain (RBD) impact neutralization. Monoclonal antibody (mAb) 222 neutralizes all three variants despite interacting with two of the ACE2-binding site mutations. We explain this through structural analysis and use the 222 light chain to largely restore neutralization potency to a major class of public antibodies.

AI snapshot

Written from the paper’s full text.

TL;DR

P.1 SARS-CoV-2 escapes many RBD-directed monoclonal antibodies but is less resistant to convalescent and vaccine serum than B.1.351, despite sharing the RBD mutations K417T/N, E484K, and N501Y. Structural and binding analyses show increased ACE2 affinity and identify mAb 222 as broadly neutralizing, with its light chain able to restore potency to other VH3-53 antibodies.

Key findings

  • P.1 RBD binds ACE2 with a KD of 4.8 nM, essentially indistinguishable from B.1.351 (4.0 nM); N501Y alone increased affinity 7-fold, and the 417/484/501 combination increased it 19-fold versus Wuhan.
  • Among 20 potent human mAbs, 12/20 showed >10-fold reduction in FRNT50 against P.1; mAb 222 neutralized all three variants, and the 150HC/222LC chimera was the most potent antibody tested against P.1 (FRNT50 3 ng/mL versus 40 ng/mL for native 150, a 13-fold increase).
  • Convalescent plasma (n = 34) neutralized P.1 with a 3.1-fold reduction versus Victoria, similar to B.1.1.7 (2.9-fold) and much less than B.1.351 (13.3-fold); vaccine serum showed 2.6-fold (Pfizer, n = 25) and 2.9-fold (AstraZeneca, n = 25) reductions against P.1.
  • Several clinical antibodies were affected: Lilly LY-CoV16 and LY-CoV555 showed almost complete loss of P.1 neutralization, REGN10933 escaped, while AZD1061, AZD7442, Adagio antibodies, and S309 were largely unaffected.

Methods

  • P.1 was cultured from a throat swab from Manaus, Brazil, December 2020, and compared with early Victoria, B.1.1.7, and B.1.351 isolates; neutralization was measured by focus reduction neutralization test (FRNT) on Vero cells.
  • Binding affinities were measured by biolayer interferometry (BLI) for RBD-ACE2 and RBD-mAb interactions; crystal structures were determined for P.1 RBD-ACE2 at 3.1 Å and six RBD-Fab 222 complexes at 1.95–2.67 Å.
  • Serum/plasma samples included 34 convalescent donors, B.1.1.7-infected donors, 25 Pfizer-BioNTech vaccinees, and 25 Oxford-AstraZeneca vaccinees; statistical comparisons used Wilcoxon matched-pairs signed rank tests and probit IC50 determination.

Limitations

  • The paper states that in vitro FRNT assays do not measure complement or antibody-dependent cell-mediated cytotoxicity, which may enhance neutralization in vivo, and that the role of T cells in protection from severe disease is unknown.
  • The paper states that directionality of cross-neutralization between variants and naturally acquired antibody responses remains to be determined, including whether B.1.351 or P.1 serum better neutralizes other strains.
  • Evident from the text: the study reports in vitro neutralization and binding/structural data only, with no in vivo protection or challenge experiments; the mAb panel is limited to 20 potent antibodies, and convalescent samples were collected before variant emergence.

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

Integrity signals

Registry

Crossref · 10.1016/j.cell.2021.03.055

Cites

58 of 58 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 60 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    The 222 light chain largely restores neutralization potency to a major class of public antibodies.

    “use the 222 light chain to largely restore neutralization potency to a major class of public antibodies”
    Quote in the paperSubstantial claim
  • Findingown data

    P.1 is significantly less resistant to naturally acquired or vaccine-induced antibody responses than B.1.351.

    “P.1 is significantly less resistant to naturally acquired or vaccine-induced antibody responses than B.1.351”
    Quote in the paperSubstantial claim
  • Findingnone given

    P.1 and B.1.351 have a virtually identical triplet of ACE2-binding-site mutations: E484K, K417N/T, and N501Y.

    “with P.1 and B.1.351 having a virtually identical triplet (E484K, K417N/T, and N501Y)”
    Quote in the paperSubstantial claim
  • Findingown data

    The P.1 and B.1.351 triplet mutations confer similar increased affinity for ACE2.

    “which we show confer similar increased affinity for ACE2”
    Quote in the paperNot a substantial claim
  • Findingown data

    P.1, B.1.1.7, and B.1.351 have accrued multiple mutations in the NTD.

    “P.1, B.1.1.7, and B.1.351 have accrued multiple mutations in the NTD.”
    Quote in the paperNot a substantial claim
  • Classified as probably not a substantial claim. 36
  • May combine two claims. 71

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

    Findingown data

    A small number of sequences including the K417T mutation, inclusive of the P.1 lineage, have been observed in Japan, France, Belgium, Italy, the Netherlands, and Colombia.

    “A small number of sequences, including the K417T mutation, inclusive of the P.1 lineage, have been observed in sequencing from Japan, France, Belgium, Italy, the Netherlands, and Colombia”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Monoclonal antibody 222 neutralizes all three variants despite interacting with two of the ACE2-binding site mutations.

    “Monoclonal antibody (mAb) 222 neutralizes all three variants despite interacting with two of the ACE2-binding site mutations.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingnone given

    P.1, B.1.351, and B.1.1.7 all have mutations in the ACE2 binding site.

    “All have mutations in the ACE2 binding site”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The second wave of infection in Manaus corresponded with rapid emergence of P.1, found in 52% of cases in December 2020 and rising to 85% by January 2021.

    “This second wave corresponded with the rapid emergence of P.1 not seen before December, when it was found in 52% of cases, rising to 85% by January 2021”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingnone given

    P.1, B.1.351, and B.1.1.7 have multiple mutations in the spike, with 12, 10, and 9 changes respectively.

    “new strains have emerged with multiple mutations, including P.1 from Brazil, B.1.351 from South Africa, and B.1.1.7 from the UK (12, 10, and 9 changes in the spike, respectively).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Mutation of RBD residue 417 to asparagine or threonine abolishes the salt bridge with 222 heavy-chain E99, leaving little direct interaction but weak (~3.5 Å) contacts to heavy-chain Y52 and light-chain Y92.

    “Mutation to either asparagine or threonine abolishes this, and there is little direct interaction, although there are weak (∼3.5 Å) contacts to heavy-chain Y52 and light-chain Y92 (Figure 4E).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingreasoning

    Most of the binding energy contribution of the 222 heavy chain comes from CDR-H1 and CDR-H2, which interact weakly with RBD residue 417.

    “Rather, it seems that there is little binding energy in general from the CDR3-H3, since most of the binding energy contribution of the heavy chain comes from CDR-H1 and CDR-H2, which interact weakly with RBD residue 417”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Neutralization by both Lilly antibodies was severely impacted, with LY-CoV16 and LY-CoV555 showing almost complete loss of neutralization of P.1 and B.1.351, and LY-CoV16 also showing marked reduction in neutralization of B.1.1.7.

    “Neutralization of both Lilly antibodies was severely impacted, with LY-CoV16 and LY-CoV555 showing almost complete loss of neutralization of P.1 and B.1.351 and LY-CoV16 also showing marked reduction in neutralization of B.1.1.7.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    At residue 484, neither the original Glu nor the Lys of P.1 makes significant contact with ACE2, but the marked change in charge substantially improves electrostatic complementarity, consistent with increased affinity.

    “neither the original Glu nor the Lys of P1 makes significant contact with ACE2; nevertheless, the marked change in charge substantially improves the electrostatic complementarity”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The P.1 isolate cultured from a throat swab from an infected patient in Manaus, Brazil in December 2020 is representative of the P.1 lineage circulating at that time.

  • May combine two claims.

    Findingown data

    The 222 light chain contains somatic mutations introducing a proline into CDR1 QSVPSSY and four changes in CDR3 QHYDTSPR.

    “the 222 LC contains somatic mutations introducing a proline into CDR1 QSVPSSY (QSVSSSY germline) and four changes in CDR3 QHYDTSPR (QQYGSSPP germline)”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The panel of 20 potent human mAbs selected from patients infected with early SARS-CoV-2 strains is representative of potent human neutralizing antibodies against SARS-CoV-2.

  • May combine two claims.

    Findingown data

    Calculation of the electrostatic potential of the contact surfaces reveals a marked change, with much greater complementarity for the P.1 RBD consistent with higher affinity.

    “calculation of the electrostatic potential of the contact surfaces reveals a marked change, with much greater complementarity for the P.1 RBD consistent with higher affinity”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The P.1 isolate cultured from a throat swab from an infected patient in Manaus, Brazil in December 2020 is representative of the P.1 lineage circulating at that time.

  • May combine two claims.

    Findingown data

    150HC/222LC showed 50-fold greater potency against B.1.351 (7 ng/mL versus 350 ng/mL) and 13-fold greater potency against P.1 (3 ng/mL versus 40 ng/mL) than native 150.

    “with the 150HC/222LC showing 50-fold greater potency against B.1.351 (7 ng/mL versus 350 ng/mL) and 13-fold greater potency against P.1 (3 ng/mL versus 40 ng/mL) than native 150.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The reduction in P.1 neutralization by convalescent plasma was similar to B.1.1.7 (2.9-fold) and considerably less than B.1.351 (13.3-fold).

    “This reduction was similar to B.1.1.7 (2.9-fold) and considerably less than B.1.351 (13.3-fold) (Figure 6C).”
    Quote in the paperSubstantial claim

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

    Findingown data

    CDR-H3 of 222 is 13 residues, slightly longer than in the majority of potent VH3-53 antibodies.

    “We note that CDR-H3 of 222, at 13 residues, is slightly longer than found in the majority of potent VH3–53 antibodies; however, this seems unlikely to be responsible for the resilience of 222.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    The escape from REGN10933 and LY-CoV555 mirrors that of other potent antibodies (including 316 and 384), which make strong interactions with residues 484-486 and are severely compromised by E484K, whereas LY-CoV16, an IGHV3-53 mAb, is affected by changes at 417 and 501.

    “The escape from REGN10933 and LY-CoV555 mirrors that of other potent antibodies (including 316 and 384 in our set), which make strong interactions with residues 484–486 and are severely compromised by the marked change E484K, whereas LY-CoV16, an IGHV3–53 mAb, is affected by changes at 417 and 501.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    The impact of P.1 on mAb binding was greater than that of B.1.1.7 but similar to that of B.1.351.

    “The results with P.1 showed an impact greater compared to B.1.1.7 but similar to B.1.351”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Zhou et al., 2021

      Not checked in the free run.

    • Rests on an assumption: The panel of 20 potent human mAbs selected from patients infected with early SARS-CoV-2 strains is representative of potent human neutralizing antibodies against SARS-CoV-2.

  • May combine two claims.

    Findingown data

    Compared to Victoria, neutralization by the mAb panel was significantly impacted by P.1, with 12/20 mAbs showing >10-fold reduction in FRNT50 titer and a number showing complete knockout of activity.

    “Compared to Victoria neutralization by the mAbs was significantly impacted by P.1, with 12/20 showing > 10-fold reduction in FRNT50 titer and a number showing complete knockout of activity”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The panel of 20 potent human mAbs selected from patients infected with early SARS-CoV-2 strains is representative of potent human neutralizing antibodies against SARS-CoV-2.

  • May combine two claims.

    Findingown data

    For B.1.1.7, neutralization by chimeras 150HC/222LC, 158HC/222LC, and 269HC/222LC was restored to near the level seen on Victoria, while 175HC/222LC could not fully neutralize B.1.1.7.

    “For B.1.1.7, neutralization of 150HC/222LC, 158HC/222LC, and 269HC/222LC was restored to near the level seen on Victoria, while 175HC/222LC could not fully neutralize B.1.1.7.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The P.1 RBD threonine at residue 417 no longer forms the salt bridge with D30 of ACE2, and the gap created is open to solvent, so there is no obvious reason why the mutation would increase affinity for ACE2.

    “The threonine of P.1 RBD no longer forms this interaction, and the gap created is open to solvent, so there is no obvious reason why the mutation would increase affinity for ACE2”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Zahradník et al., 2021

      Not checked in the free run.

    • Rests on an assumption: The P.1 isolate cultured from a throat swab from an infected patient in Manaus, Brazil in December 2020 is representative of the P.1 lineage circulating at that time.

  • May combine two claims.

    Findingown data

    The crystal structures of 222 Fab with RBDs of the original virus and variants K417N, K417T, N501Y, B.1.351-like, and P.1 are highly similar, with the binding pose of 222 essentially identical in all structures (pairwise RMSD ~0.2-0.3 Å).

    “As expected, the structures are highly similar, with the binding pose of 222 being essentially identical in all structures (pairwise RMSD in Cα atoms between pairs of structures are ∼0.2–0.3 Å for all residues in the RBD and Fv region of mAb 222 (Figure 4D).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The neutralization titer of NTD-binding mAb159 was 133-fold reduced on P.1 compared to Victoria, with only 64% neutralization at 10 μg/mL.

    “The neutralization titer of NTD-binding mAb159 was 133-fold reduced on P.1 compared to Victoria, with only 64% neutralization at 10 μg/mL”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The panel of 20 potent human mAbs selected from patients infected with early SARS-CoV-2 strains is representative of potent human neutralizing antibodies against SARS-CoV-2.

  • May combine two claims.

    Findingown data

    The RMSD between the 791 Cα positions is 0.4 Å, similar to experimental error, and the local structure around each of the three mutations is conserved.

    “The root mean square deviation (RMSD) between the 791 Cα positions is 0.4 Å, similar to the experimental error in the coordinates, and the local structure around each of the three mutations is conserved.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The P.1 isolate cultured from a throat swab from an infected patient in Manaus, Brazil in December 2020 is representative of the P.1 lineage circulating at that time.

  • May combine two claims.

    Findingcitation

    The impact of P.1 on mAb neutralization was greater than that of B.1.1.7 but similar to that of B.1.351.

    “The results with P.1 showed a greater impact compared to B.1.1.7 but were, as expected, similar to those with B.1.351”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Zhou et al., 2021

      Not checked in the free run.

    • Rests on an assumption: The panel of 20 potent human mAbs selected from patients infected with early SARS-CoV-2 strains is representative of potent human neutralizing antibodies against SARS-CoV-2.

  • May combine two claims.

    Findingown data

    The KD for the P.1-ACE2 interaction is 4.8 nM, with Kon = 1.08E5/Ms and Koff = 5.18E-4/s.

    “The KD for the P.1-ACE2 interaction is 4.8 nM, with Kon = 1.08E5/Ms and Koff = 5.18E-4/s”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The P.1 isolate cultured from a throat swab from an infected patient in Manaus, Brazil in December 2020 is representative of the P.1 lineage circulating at that time.

  • May combine two claims.

    Findingown data

    S309 Vir was largely unaffected, although for several viruses including P.1 the antibody failed to completely neutralize.

    “S309 Vir was largely unaffected, although for several viruses, including P.1, the antibody failed to completely neutralize”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The three Adagio antibodies neutralized all variants, with all reaching a plateau at 100% neutralization; ADG30 showed a slight increase of neutralization of P.1.

    “The three Adagio antibodies neutralized all variants, with all reaching a plateau at 100% neutralization; interestingly, ADG30 showed a slight increase of neutralization of P.1.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Neutralization of P.1 by mAbs 175 and 158 is severely impacted, and neutralization of P.1 by mAb 269 is almost completely lost.

    “Neutralization of P.1 by 175 and 158 is severely impacted, and neutralization of P.1 by 269 is almost completely lost.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The panel of 20 potent human mAbs selected from patients infected with early SARS-CoV-2 strains is representative of potent human neutralizing antibodies against SARS-CoV-2.

  • May combine two claims.

    Findingcitation

    Residue 188 is somewhat occluded, whereas residue 20 is highly exposed, close to the site of attachment of neutralizing antibody 159, and impinges on the proposed NTD supersite.

    “Residue 188 is somewhat occluded, whereas residue 20 is highly exposed, is close to the site of attachment of neutralizing antibody 159 (Dejnirattisai et al., 2021), and impinges on the proposed NTD supersite.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Dejnirattisai et al., 2021 source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    For mAb 150, P.1 neutralization is less compromised than for B.1.351, while for mAb 222, neutralization is completely unaffected by the changes in P.1 and all variants.

    “for 150 P.1 neutralization is less compromised than for B.1.351 (Zhou et al., 2021), while for 222, neutralization is completely unaffected by the changes in P.1 and indeed all variants”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Zhou et al., 2021

      Not checked in the free run.

    • Rests on an assumption: The panel of 20 potent human mAbs selected from patients infected with early SARS-CoV-2 strains is representative of potent human neutralizing antibodies against SARS-CoV-2.

  • May combine two claims.

    Findingown data

    There was escape from neutralization of P.1 by REGN10933 and a modest reduction in neutralization of P.1 by AZD8895, while AZD1061 and AZD7442 showed equal neutralization of all SARS-CoV-2 variants.

    “There was also escape from neutralization of P.1 by REGN10933 and a modest reduction in neutralization of P.1 by AZD8895, while AZD1061 and AZD 7442 showed equal neutralization of all SARS-CoV-2 variants.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Among the 100 most similar sequences to the 222 light chain in the PDB, only 1 had a proline at the position corresponding to P30, indicating this somatic mutation is rare.

    “Using the 222 LC (omitting the first three and the last 20 residues of the VL domain to focus the search on the L1 region) to do a BLAST search of the PDB (Table S3), only 1 of the 100 most similar sequences had a proline in this position, indicating that this somatic mutation is a rare occurrence.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The NTD has multiple mutations in all three major variant strains: B.1.1.7 has two deletions, B.1.351 has a deletion and four substitutions, and P.1 has five amino acid substitutions, including creation of two N-linked glycan sequons.

    “this domain has multiple mutations in all three major variant strains; B.1.1.7 has two deletions, B.1.351 has a deletion and four substitutions, and P.1 has five amino acid substitutions, including the creation of two N-linked glycan sequons (Figures 1A–1C).”
    Quote in the paperSubstantial claim

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

    Findingnone given

    There is some suggestion in this report that plasma induced by B.1.1.7 is better able to neutralize B.1.351 and P.1.

    “For instance, there is some suggestion in this report that plasma induced by B.1.1.7 is better able to neutralize B.1.351 and P.1.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The P.1 RBD has increased affinity for ACE2 equivalent to B.1.351 and somewhat tighter than B.1.1.7.

    “In this paper, we demonstrate an increase in affinity of interaction for P.1 RBD with ACE2 to an equivalent degree as that observed for B.1.351, with binding somewhat tighter than for B.1.1.7.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Neutralization titers against P.1 were similar to those against B.1.1.7, and only a minority of samples failed to reach 100% neutralization at 1:20 dilution of serum.

    “Neutralization titers against P.1 were similar to those against B.1.1.7, and only a minority of samples failed to reach 100% neutralization at 1:20 dilution of serum”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The changes in the NTD of the major variants are far less consistent than those in the RBD, and there are no strong trends in electrostatic properties.

    “The changes in the NTD of the major variants are far less consistent than those found in the RBD, and there are no strong trends in electrostatic properties (Figures 1A–1C).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Using convalescent serum, B.1.351 showed 13-fold reduction in neutralization compared to Victoria, while P.1 was only reduced 3.1-fold, comparable to B.1.1.7.

    “Using convalescent serum, B.1.351 showed 13-fold reduction in neutralization compared to Victoria, while P.1 was only reduced 3.1-fold, comparable to the reduction seen with B.1.1.7, which only harbors the single N501Y change in the RBD (Zhou et al., 2021; Supasa et al., 2021).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Zhou et al., 2021

      Not checked in the free run.

    • cites Supasa et al., 2021 source

      Not checked in the free run.

  • May combine two claims.

    Findingnone given

    In contrast to B.1.351, neutralization of P.1 does not show such a substantial reduction by polyclonal serum induced by natural infection or vaccination, and there is no evidence of widespread escape.

    “In contrast to B.1.351, neutralization of P.1 does not show such a substantial reduction by polyclonal serum induced by natural infection or vaccination, and there is no evidence of widespread escape.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    P.1 can escape neutralization by a number of mAbs, including some being developed for prophylactic or therapeutic use, while other antibodies with epitopes away from mutated RBD residues retain broad neutralization.

    “In summary, we demonstrate that P.1 can escape neutralization by a number of mAbs, including some being developed for prophylactic or therapeutic use, while other antibodies with epitopes away from the mutated RBD residues retain broad neutralization.”
    Quote in the paperSubstantial claim

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

    Findingnone given

    The ChCl domains of EY6A are flexible and have poor electron density.

    “The ChCl domains of EY6A are flexible and have poor electron density.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Crystals of P.1 RBD/ACE2 complex were formed in Hampton Research PEGRx 1 screen, condition 38, containing 0.1 M Imidazole pH 7.0 and 20% w/v Polyethylene glycol 6,000.

    “Crystals of P.1 RBD/ACE2 complex were formed in Hampton Research PEGRx 1 screen, condition 38, containing 0.1 M Imidazole pH 7.0 and 20% w/v Polyethylene glycol 6,000.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Findingown data

    Structures of WT RBD-EY6A-222 and the P.1 RBD-ACE2 complexes were determined by molecular replacement with PHASER using search models of SARS-CoV-2 RBD-EY6A-H4 (PDB ID 6ZCZ), RBD-158 (PDB ID 7BEK), and a RBD and ACE2 complex (PDB ID 6LZG).

    “Structures of WT RBD-EY6A-222 and the P.1 RBD-ACE2 complexes were determined by molecular replacement with PHASER (McCoy et al., 2007) using search models of SARS-CoV-2 RBD-EY6A-H4 (PDB ID 6ZCZ) (Zhou et al., 2020) and RBD-158 (PDB ID, 7BEK) (Dejnirattisai et al., 2021) complexes, and a RBD and ACE2 complex (PDB ID, 6LZG; Wang et al., 2020), respectively.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites McCoy et al., 2007 source

      Not checked in the free run.

    • cites Zhou et al., 2020 source

      Not checked in the free run.

    • cites Dejnirattisai et al., 2021 source

      Not checked in the free run.

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

    Findingown data

    Good crystals of EY6A Fab and 222 Fab complexed with WT, K417T, K417N, B.1.1.7, B.1.351 or P.1 RBD were all obtained from Hampton Research PEGRx 2 screen, condition 35, containing 0.15 M Lithium sulfate, 0.1 M Citric acid pH 3.5, 18% w/v PEG 6,000.

    “Good crystals of EY6A Fab and 222 Fab complexed with WT, K417T, K417N, B.1.1.7, B.1.351 or P.1 RBD were all obtained from Hampton Research PEGRx 2 screen, condition 35, containing 0.15 M Lithium sulfate, 0.1 M Citric acid pH 3.5, 18% w/v PEG 6,000.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    The RBD interacts with ACE2, which is expressed on diverse cell types including cells in the upper and lower respiratory tracts, allowing SARS-CoV-2 to cause respiratory infection.

    “The RBD interacts with the cellular receptor angiotensin converting enzyme 2 (ACE2), which is expressed on diverse cell types, including cells in the upper and lower respiratory tracts, allowing SARS-CoV-2 to cause respiratory infection.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Hoffmann et al., 2020 source

      Not checked in the free run.

    • cites Shang et al., 2020 source

      Not checked in the free run.

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

    Premisenone given

    P.1 has three RBD changes (K417T, E484K, N501Y), B.1.351 has three RBD changes (K417N, E484K, N501Y), and B.1.1.7 contains the single N501Y mutation.

    “P.1 has three changes in the RBD (K417T, E484K, and N501Y), which are a particular cause for concern. B.1.351 also has three changes in the RBD (K417N, E484K, and N501Y), whereas B.1.1.7 contains the single N501Y mutation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Three multiply mutated viral strains appeared independently at the end of 2020 in different regions and rapidly expanded to become dominant strains.

    “Three multiply mutated viral strains appeared independently at the end of 2020 in different regions, where they rapidly expanded to become the dominant strains”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites https://www.cogconsortium.uk/wp-content/uploads/2021/01/Report-2_COG-UK_SARS-CoV-2-Mutations.pdf

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    B.1.1.7 has two NTD deletions (Δ69-70 and Δ144); B.1.351 has four NTD amino acid changes and the Δ242-244 deletion; P.1 has six NTD amino acid changes but no deletions.

    “In B.1.1.7, there are two deletions (Δ69–70 and Δ144). In B.1.351. there are four amino acid changes and the Δ242–244 deletion, while in P.1, there are six amino acid changes in the NTD but no deletions.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premiseown data

    Compared to the Wuhan sequence, P.1 contains L18F, T20N, P26S, D138Y, and R190S in the NTD; K417T, E484K, and N501Y in the RBD; D614G and H655Y at the C terminus of S1; and T1027I and V1176F in S2.

    “Compared to the Wuhan sequence, P.1 contains the following mutations: L18F, T20N, P26S, D138Y, and R190S in the NTD; K417T, E484K, and N501Y in the RBD; D614G and H655Y at the C terminus of S1; and T1027I and V1176F in S2.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Mutations in S may give SARS-CoV-2 a selective advantage through increased efficiency of transmission or escape from neutralizing antibodies.

    “concentrating on mutation in S, there are two clear possibilities: increased efficiency of transmission and escape from neutralizing antibodies”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Volz et al., 2021 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    The ACE2 interaction surface is a small 25-amino-acid patch at the apex of spike, presented to ACE2 when the RBD swings upward.

    “The ACE2 interaction surface is a small 25-amino-acid patch at the apex of spike, presented to ACE2 when the RBD swings upward”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Hoffmann et al., 2020 source

      Not checked in the free run.

    • cites Shang et al., 2020 source

      Not checked in the free run.

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

    Premisenone given

    The RBD changes have the potential to modulate ACE2/RBD affinity, potentially leading to increased transmissibility, for which there is now good evidence in B.1.1.7.

    “All of these changes have the potential to modulate ACE2/RBD affinity, potentially leading to increased transmissibility, for which there is now good evidence in B.1.1.7.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    P.1 was first reported in December 2020 from Manaus in Amazonas province of Northern Brazil.

    “P.1 was first reported in December 2020 from Manaus in Amazonas province of Northern Brazil”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Faria et al., 2021

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Structures of mAbs 150, 158, and 269 show no contacts with residue 484, interactions of CDR-H3 with K417 and CDR-L1 with N501, meaning binding and neutralization by VH3-53 antibodies would be predicted to be compromised by N501Y, while the additional change at 417 might have an additive effect.

    “while there are no contacts with residue 484, there are interactions of CDR-H3 with K417 and CDR-L1 with N501, meaning that binding and neutralization by VH3–53 antibodies would be predicted to be compromised by the N501Y change in variant viruses B.1.1.7, B.1.351, and P.1, while the additional change at 417 in P.1 (K417T) and B.1.351 (K417N) might be expected to have an additive effect”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Dejnirattisai et al., 2021 source

      Not checked in the free run.

  • May combine two claims.

    Premiseown data

    Five potent mAbs used in the study (150, 158, 175, 222, and 269) belong to the VH3-53 family, and a further two belong to the almost identical VH3-66 family.

    “Five of our potent mAbs used in this study (150, 158, 175, 222, and 269) belong to the VH3–53 family, and a further two (out of five of this family) belong to the almost identical VH3–66”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The panel of 20 potent human mAbs selected from patients infected with early SARS-CoV-2 strains is representative of potent human neutralizing antibodies against SARS-CoV-2.

  • May combine two claims.

    Interpretationreasoning

    The N-terminal residues preceding residue 18 interact with mAb159 and may be perturbed.

    “the N-terminal residues preceding residue 18 interact with the antibody and may be perturbed”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The P.1 isolate cultured from a throat swab from an infected patient in Manaus, Brazil in December 2020 is representative of the P.1 lineage circulating at that time.

  • May combine two claims.

    Premisecitation

    LY-CoV555 is sensitive to mutation at residue 484 and LY-CoV16 is sensitive to changes at 417.

    “LY-CoV555 is sensitive to mutation at residue 484 and LY-CoV16 is sensitive to changes at 417”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Starr and Greaney, 2021

      Not checked in the free run.

    • cites Greaney et al., 2021 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The 222 light chain might be an almost universal light chain for VH3-53 antibodies and could confer resilience to P.1, B.1.1.7, and B.1.351 variants.

    “This suggests that the 222 light chain might be an almost universal light chain for these 3–53 antibodies and could confer resilience to P.1, B.1.1.7, and B.1.351 variants.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    The N501Y mutation probably slightly strengthens the interaction with P30 by providing a stacking interaction with the proline, conferring resilience.

    “however, the interaction with P30 is probably slightly strengthened by the N501Y mutation, which provides a stacking interaction with the proline, conferring resilience.”
    Quote in the paperNot a substantial claim

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

    Premisenone given

    VH3-53 are the most prevalent deposited sequences and structures for SARS-CoV-2 neutralizing antibodies.

    “VH3–53 are the most prevalent deposited sequences and structures for SARS-CoV-2 neutralizing antibodies.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    N501Y increased RBD-ACE2 affinity 7-fold, and the combination of 417, 484, and 501 mutations further increased affinity 19-fold compared to Wuhan.

    “N501Y increased affinity 7-fold, and the combination of 417, 484, and 501 mutations further increased affinity (19-fold compared to Wuhan).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Zhou et al., 2021

      Not checked in the free run.

    • cites Supasa et al., 2021 source

      Not checked in the free run.

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

    Premisecitation

    A single bare patch surrounded by N-linked glycans attached at N17, N74, N122, and N149 defines a supersite limiting where neutralizing antibodies can attach to the NTD.

    “it has been suggested that a single bare patch surrounded by N-linked glycans attached at N17, N74, N122, and N149 defines a “supersite” limiting where neutralizing antibodies can attach to the NTD”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Cerutti et al., 2021

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    VH3-53 antibody engagement with the RBD is dictated by CDR-H1 and CDR-H2, while the CDR-H3 is characteristically short and makes rather few interactions.

    “Their engagement with the RBD is dictated by CDR-H1 and CDR-H2, while the CDR-H3 is characteristically short and makes rather few interactions”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Yuan et al., 2020 source

      Not checked in the free run.

    • cites Barnes et al., 2020 source

      Not checked in the free run.

    • cites Dejnirattisai et al., 2021 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    For B.1.351, Novavax and Janssen vaccines showed marked decrease in efficacy but still >50% protection against moderate and severe disease.

    “For B.1.351, both the Novavax (https://www.webmd.com/vaccines/covid-19-vaccine/news/20210131/vaccine-not-as-effective-against-south-african-variant) and Janssen vaccines (https://www.reuters.com/article/us-health-coronavirus-vaccines-johnson-j-idUSKBN29Z0F0) saw a marked decrease in efficacy but still showed >50% protection”
    Quote in the paperNot a substantial claim

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

    Interpretationreasoning

    It remains unclear what drives the NTD changes, although immune escape, co-receptor binding, and modulation of RBD dynamics are plausible.

    “It therefore remains unclear what the drivers are for these changes, although one or more of immune escape, co-receptor binding, and modulation of RBD dynamics affecting presentation of the receptor binding site are plausible.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Clinical evidence shows ChAdOx1 nCoV-19 Oxford-AstraZeneca and NVX-CoV2373 Novavax vaccines provide protection from B.1.1.7.

    “There is now clinical evidence that the ChAdOx1 nCoV-19 Oxford-AstraZeneca and NVX-CoV2373 Novavax vaccines provide protection from B.1.1.7 (Emary et al., 2021; Mahase, 2021).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Emary et al., 2021 source

      Not checked in the free run.

    • cites Mahase, 2021 source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    P.1 contains 12 individual changes spread throughout S, with three changes in the RBD.

    “P.1 contains 12 individual changes spread throughout S, with three changes in the RBD.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    Written informed consent was obtained for all patients enrolled in the Pfizer vaccinee study.

    “Written informed consent was obtained for all patients enrolled in the study.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Highly effective natural responses against all three variants and common cross-protective responses will be found.

    “This also suggests that highly effective natural responses against all three variants and common cross-protective responses will be found.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    The AstraZeneca-Oxford vaccine trials were done in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice.

    “Written informed consent was obtained from all participants, and the trial is being done in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    The AstraZeneca-Oxford vaccine studies were sponsored by the University of Oxford and approved by a national ethics committee (South Central Berkshire Research Ethics Committee, reference 20/SC/0145 and 20/SC/0179) and a regulatory agency in the United Kingdom (the Medicines and Healthcare Products Regulatory Agency).

    “The studies were sponsored by the University of Oxford (Oxford, UK) and approval obtained from a national ethics committee (South Central Berkshire Research Ethics Committee, reference 20/SC/0145 and 20/SC/0179) and a regulatory agency in the United Kingdom (the Medicines and Healthcare Products Regulatory Agency).”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    Written informed consent was obtained from all participants in the AstraZeneca-Oxford vaccine studies.

    “Written informed consent was obtained from all participants, and the trial is being done in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice.”
    Quote in the paperNot a substantial claim

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

    Interpretationnone given

    The emergence of B.1.1.7 occurred on a background of relatively low population immunity and may have been primarily driven by increased transmissibility.

    “The emergence of B.1.1.7 occurred on the background of relatively low population immunity and may have been primarily driven by increased transmissibility.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    Victoria passage 5, B.1.1.7 passage 2, and B.1.351 passage 4 stocks were sequenced to verify that they contained the expected S protein sequence and no changes to the furin cleavage sites.

    “Victoria passage 5, B.1.1.7 passage 2 and B.1.351 passage 4 stocks were sequenced to verify that they contained the expected S protein sequence and no changes to the furin cleavage sites.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    B.1.351 emerged on a background of ~30% seropositivity in South Africa, and P.1 emerged on a background of an estimated 75% seropositivity in Manaus, Brazil.

    “The emergence of B.1.351 occurred on the background of ∼30% seropositivity in South Africa and P.1 on the background of an estimated 75% seropositivity in Manaus, Brazil (Faria et al., 2021).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Faria et al., 2021

      Not checked in the free run.

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

    Interpretationreasoning

    Selection of P.1 and B.1.351 may have been in part driven by immune escape.

    “It seems possible that selection of P.1 and B.1.351 may have been in part driven by immune escape”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Based on the results, B.1.351 is the variant of greatest concern, giving the largest reductions in neutralization titers and evidence of complete failure to neutralize in some cases.

    “Based on the results reported here, the South African B.1.351 is the variant of greatest concern, giving the largest reductions in neutralization titers and evidence of complete failure to neutralize in some cases”
    Quote in the paperSubstantial claim

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

    Study design and conductown data

    Passage 1 P.1 virus was sequence confirmed and contained no changes to the furin cleavage site.

    “Passage 1 P.1 virus was sequence confirmed and contained no changes to the furin cleavage site.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The ACE2 interacting surface of RBD is a small 25-amino-acid patch at the apex of S and is under extreme selection pressure because it mediates receptor interaction and is the binding site for a major class of neutralizing antibodies.

    “The ACE2 interacting surface of RBD is a small 25-amino-acid patch at the apex of S and is under extreme selection pressure, as it mediates interaction with the cellular receptor and is also the site of binding for a major class of neutralizing antibodies that block the interaction of ACE2 with the RBD (Zost et al., 2020; Kreye et al., 2020; Wu et al., 2020; Yuan et al., 2020; Dejnirattisai et al.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Zost et al., 2020 source

      Not checked in the free run.

    • cites Kreye et al., 2020 source

      Not checked in the free run.

    • cites Wu et al., 2020

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Polyclonal anti-SARS-CoV-2 serum selected mutant RBDs from a yeast display library with reduced antibody binding, identifying potential escape mutants including E484K.

    “In a second approach, polyclonal anti-SARS-CoV-2 serum was used to select mutant RBD from a yeast display library that showed reduced antibody binding (Greaney et al., 2021). This approach led to the identification of a number of potential antibody escape mutants, among them E484K”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Greaney et al., 2021 source

      Not checked in the free run.

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

    Study design and conductnone given

    All constructs were verified by sequencing.

    “All constructs were verified by sequencing.”
    Quote in the paperNot a substantial claim

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

    Interpretationcitation

    The increase in receptor affinity may drive increased virus transmissibility, allowing the three variants to become dominant strains in the regions where they emerged.

    “It seems conceivable that this increase in receptor affinity may drive increased virus transmissibility, allowing the three variants to become dominant strains in the regions where they emerged (Zhou et al., 2021; Supasa et al., 2021).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Zhou et al., 2021

      Not checked in the free run.

    • cites Supasa et al., 2021 source

      Not checked in the free run.

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

    Study design and conductnone given

    Clinical samples (throat swabs) containing P.1 were shared with Oxford University, UK under the MTA IOC FIOCRUZ 21-02.

    “Clinical samples (throat swabs) containing P.1 were shared with Oxford University, UK under the MTA IOC FIOCRUZ 21-02.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Public antibody responses for SARS-CoV-2 include principally VH3-53/VH3-66 and VH1-58, with VH3-30 also found but not potent neutralizers.

    “A number of public antibody responses have been reported for SARS-CoV-2, principal among these being VH3–53/VH3–66 and VH1–58 (VH3–30 is also found, but the antibodies are not potent neutralizers) (Yuan et al., 2020; Barnes et al., 2020; Dejnirattisai et al., 2021).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Yuan et al., 2020 source

      Not checked in the free run.

    • cites Barnes et al., 2020 source

      Not checked in the free run.

    • cites Dejnirattisai et al., 2021 source

      Not checked in the free run.

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

    Study design and conductnone given

    The Pfizer vaccinee study was conducted according to the principles of the Declaration of Helsinki (2008) and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines.

    “The study was conducted according to the principles of the Declaration of Helsinki (2008) and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Interpretationreasoning

    Creation of such antibody chimeras among other anti-SARS-CoV-2 antibodies may lead to discovery of more antibodies with enhanced activity.

    “Creation of such antibody chimeras among other anti-SARS-CoV-2 antibodies may similarly lead to the discovery of more antibodies with enhanced activity.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Diagnosis of participants was confirmed through reporting of symptoms consistent with COVID-19 and a test positive for SARS-CoV-2 using RT-PCR from an upper respiratory tract swab tested in accredited laboratories.

    “Diagnosis was confirmed through reporting of symptoms consistent with COVID-19 and a test positive for SARS-CoV-2 using reverse transcriptase polymerase chain reaction (RT-PCR) from an upper respiratory tract (nose/throat) swab tested in accredited laboratories.”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given

    The International Reference Laboratory for Coronavirus at FIOCRUZ (WHO) had approval from the FIOCRUZ ethical committee (CEP 4.128.241) to continuously receive and analyze samples of COVID-19 suspected cases for virological surveillance.

    “The International Reference Laboratory for Coronavirus at FIOCRUZ (WHO) as part of the national surveillance for coronavirus had the approval of the FIOCRUZ ethical committee (CEP 4.128.241) to continuously receive and analyze samples of COVID-19 suspected cases for virological surveillance.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    Vaccinees from whom Pfizer vaccine serum was obtained were Health Care Workers based at Oxford University Hospitals NHS Foundation Trust, not known to have prior infection with SARS-CoV-2.

    “Vaccinees were Health Care Workers, based at Oxford University Hospitals NHS Foundation Trust, not known to have prior infection with SARS-CoV-2 and were enrolled in the OPTIC Study as part of the Oxford Translational Gastrointestinal Unit GI Biobank Study 16/YH/0247 [research ethics committee (REC) at Yorkshire & The Humber – Sheffield].”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given

    The AstraZeneca-Oxford vaccine studies were registered at ISRCTN (15281137 and 89951424) and ClinicalTrials.gov (NCT04324606 and NCT04400838).

    “These studies were registered at ISRCTN (15281137 and 89951424) and ClinicalTrials.gov (NCT04324606 and NCT04400838).”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Recent findings suggest that CD4 and CD8 T cell responses raised to ancestral strains are minimally impacted by the variants.

    “but recent findings suggest that CD4 and CD8 T cell responses raised to ancestral strains are minimally impacted by the variants (Tarke et al., 2021; Skelly et al., 2021).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Tarke et al., 2021

      Not checked in the free run.

    • cites Skelly et al., 2021

      Not checked in the free run.

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

    Study design and conductnone given

    An independent DSMB reviewed all interim safety reports for the AstraZeneca-Oxford vaccine studies.

    “An independent DSMB reviewed all interim safety reports.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In a phase 2 trial, ChAdOx1 nCoV-19 efficacy against mild to moderate disease caused by B.1.351 was 10.4% (95% CI −76.8; 43.8), but efficacy against severe disease could not be assessed.

    “while in a phase 2 trial, ChAdOx1 nCoV-19 efficacy against mild to moderate disease caused by B.1.351 was 10.4% (95% confidence interval [CI] −76.8; 43.8), but efficacy against severe disease could not be assessed in this study (Madhi et al., 2021).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Madhi et al., 2021

      Not checked in the free run.

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

    Premisecitation

    The constructs of EY6A Fab, 222 Fab, ACE2, WT RBD, B.1.1.7 and B.1.351 mutant RBD are the same as previously described.

    “The constructs of EY6A Fab, 222 Fab, ACE2, WT RBD, B.1.1.7 and B.1.351 mutant RBD are the same as previously described (Dejnirattisai et al., 2021; Zhou et al., 2021; Supasa et al., 2021).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Dejnirattisai et al., 2021 source

      Not checked in the free run.

    • cites Zhou et al., 2021

      Not checked in the free run.

    • cites Supasa et al., 2021 source

      Not checked in the free run.

93 of 93

  • The paper relies on this without support.

    The P.1 isolate cultured from a throat swab from an infected patient in Manaus, Brazil in December 2020 is representative of the P.1 lineage circulating at that time.

    “we examine an isolate of P.1 cultured from a throat swab taken from an infected patient in Manaus, Brazil in December 2020”

  • The paper relies on this without support.

    The panel of 20 potent human mAbs selected from patients infected with early SARS-CoV-2 strains is representative of potent human neutralizing antibodies against SARS-CoV-2.

    “From this panel, we have selected 20 potent antibodies that have focus reduction neutralization 50% (FRNT50) values <100 ng/mL”

  • The paper relies on this without support.

    Neutralization titers measured by in vitro FRNT are a correlate of protection against SARS-CoV-2 in vivo.

    “Similarly, neutralization of P.1 by vaccine serum was less impacted than neutralization of B.1.351, meaning that vaccination with Wuhan S will likely provide some protection against P.1.”
3 of 3

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?

  • A similar distribution in the reduction in neutralizing activity was observed in plasma samples from recipients of the AZD1222 vaccine against the Gamma variant.

    “A similar distribution in the reduction in neutralizing activity was observed in plasma samples from recipients of the AZD1222 vaccine 103 .”

    From The biological and clinical significance of emerging SARS-CoV-2 variants (2021) · cites this paper as [103]

  • Of plasma samples from persons receiving one of the two authorized mRNA vaccines, about 60% had 3-fold to 10-fold and 5% had >10-fold reduced neutralizing activity to the Gamma variant.

    “Of plasma samples from persons receiving one of the two authorized mRNA vaccines, about 60% had 3-fold to 10-fold and 5% had >10-fold reduced neutralizing activity 97,103,117,167,217,230 (fIg.5).”

    From The biological and clinical significance of emerging SARS-CoV-2 variants (2021) · cites this paper as [103]

  • The resistance profile of the Gamma variant to the FDA EUA-approved mAbs is similar to that of the Beta variant.

    “The resistance profile of the Gamma vari ant to the FDA EUA-approved mAbs is similar to that of the Beta variant 103,109,217,227,228 (TABLe 1).”

    From The biological and clinical significance of emerging SARS-CoV-2 variants (2021) · cites this paper as [103]

  • Of convalescent plasma samples obtained from persons infected with early pandemic variants or with the Alpha variant, about 20% had 3-fold to 10-fold and 10% had >10-fold reduced neutralizing activity to the Gamma variant.

    “Of convalescent plasma samples obtained from persons infected with early pandemic variants or with the Alpha variant, about 20% had 3-fold to 10-fold and 10% had >10-fold reduced neutralizing activity 97,103,117,203,217,228,229 (fIg.5).”

    From The biological and clinical significance of emerging SARS-CoV-2 variants (2021) · cites this paper as [103]

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.

  • Pfizer serum collection windows disagree

    Minor

    The Results give the collection window as 4-14 days after the second dose, whereas the Figure 7 caption gives 7-17 days for the Pfizer serum samples.

  • The tested P.1 virus has a different RBD mutation in the methods

    Minor

    The Results identify E484K as one of P.1's three RBD mutations, but the viral-stocks section lists E464K for the P.1 virus used in the study. This leaves the identity of a conclusion-bearing mutation in the tested virus inconsistent.

  • P.1 NTD mutation count differs from the listed mutations

    Minor

    The paper says P.1 has six NTD amino acid changes, but its explicit list contains five: L18F, T20N, P26S, D138Y, and R190S.

3 of 3

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Authors
Dejnirattisai, W., Zhou, D., Supasa, P., Liu, C., Mentzer, A. J., Ginn, H. M., Zhao, Y., Duyvesteyn, H. M. E., Tuekprakhon, A., Nutalai, R., Wang, B., López-Camacho, C., Slon-Campos, J., Walter, T. S., Skelly, D., Costa Clemens, S. A., Naveca, F. G., Nascimento, V., Nascimento, F., Fernandes da Costa, C., Resende, P. C., Pauvolid-Correa, A., Siqueira, M. M., Dold, C., Levin, R., Dong, T., Pollard, A. J., Knight, J. C., Crook, D., Lambe, T., Clutterbuck, E., Bibi, S., Flaxman, A., Bittaye, M., Belij-Rammerstorfer, S., Gilbert, S. C., Carroll, M. W., Klenerman, P., Barnes, E., Dunachie, S. J., Paterson, N. G., Williams, M. A., Hall, D. R., Hulswit, R. J. G., Bowden, T. A., Fry, E. E., Mongkolsapaya, J., Ren, J., Stuart, D. I., & Screaton, G. R.
Affiliations
  • Centre for Human Genetics (GB)
  • Diamond Light Source (GB)
  • University of Siena (IT)
  • Fiocruz Amazônia (BR)
  • Instituto Oswaldo Cruz (BR)
  • University of Oxford (GB)
  • Worthing Hospital (GB)
  • Siriraj Hospital (TH)
Corresponding author
  • Mongkolsapaya, Juthathip
  • Ren, Jingshan
  • Stuart, David I.
  • Screaton, Gavin R.
ORCID
Venue
Cell
Publisher
Elsevier BV
Published
2021-05
Volume
184
Issue
11
Pages
2939-2954.e9
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2021.03.055
PMC
PMC8008340
OpenAlex
W3142246475
Semantic Scholar
24fe4fef4c04da16e81ffc7178cf7eacf4656cdc
Cited by
583
References
58
Citations by year
2026: 7 · 2025: 20 · 2024: 39 · 2023: 77 · 2022: 237 · 2021: 202
FWCI
44.02
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Arca - Repositório Institucional da Fiocruz (submittedVersion, other-oa)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
  • Greater South Information System
Funders
  • Cancer Research UK Lincoln&apos;s Inn Fields Laboratories (C375/A17721)
  • Huo Family Foundation
  • Chinese Academy of Medical Sciences and Peking Union Medical College (2018-I2M-2-002)
  • UK Research and Innovation
  • World Health Organization (PCT/GB2012/000467)
  • National Institute for Health and Care Research
  • Coalition for Epidemic Preparedness Innovations
  • Department of Health and Social Care
  • NIHR Oxford Biomedical Research Centre
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico (403276/2020-9)
  • National Institutes of Health (WT204969/Z/16/Z, U19 I082360)
  • Wellcome Trust (203141/Z/16/Z, 095541/A/11/Z, 101122/Z/13/Z, 090532/Z/09/Z)
  • Public Health England
  • Fundação de Amparo à Pesquisa do Estado do Amazonas
  • Medical Research Council (ACE2, MR/S007555/1)
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
SARS-CoV-2, P.1 variant, antibody escape, neutralizing antibodies, E484K, N501Y, spike protein, Beta variant, Alpha variant, receptor binding domain, antibody structure, vaccine-induced immunity, natural immunity
MeSH terms
Protein Domains, COVID-19, SARS-CoV-2, COVID-19 Serotherapy, Antibodies, Monoclonal, Antibodies, Viral, Binding Sites, Cell Line, Humans, Immunization, Passive, Mutation, Protein Binding, Vaccination, Vaccines, Sequence Deletion, Immune Evasion, Antibodies, Neutralizing, Spike Glycoprotein, Coronavirus

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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

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