CoChat
Sign Up
Cited by 992SARS-CoV-2 and COVID-19 Researchvaccines and immunoinformatics approachesAnimal Virus Infections Studies

Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine-induced sera

Open access
Zhou, Daming, Dejnirattisai, Wanwisa, Supasa, Piyada, Liu, Chang, Mentzer, Alexander J., Ginn, Helen M., Zhao, Yuguang, Duyvesteyn, Helen M.E. +36 more·2021·Cell
DOI 10.1016/j.cell.2021.02.037PMC PMC7901269
Open this paper in CoChat — free account

Abstract

The race to produce vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began when the first sequence was published, and this forms the basis for vaccines currently deployed globally. Independent lineages of SARS-CoV-2 have recently been reported: UK, B.1.1.7; South Africa, B.1.351; and Brazil, P.1. These variants have multiple changes in the immunodominant spike protein that facilitates viral cell entry via the angiotensin-converting enzyme-2 (ACE2) receptor. Mutations in the receptor recognition site on the spike are of great concern for their potential for immune escape. Here, we describe a structure-function analysis of B.1.351 using a large cohort of convalescent and vaccinee serum samples. The receptor-binding domain mutations provide tighter ACE2 binding and widespread escape from monoclonal antibody neutralization largely driven by E484K, although K417N and N501Y act together against some important antibody classes. In a number of cases, it would appear that convalescent and some vaccine serum offers limited protection against this variant.

AI snapshot

Written from the paper’s full text.

TL;DR

This structure-function study shows that SARS-CoV-2 variant B.1.351 escapes neutralization by many monoclonal antibodies and by convalescent and vaccinee sera, largely due to RBD mutations K417N, E484K, and N501Y. B.1.351 RBD binds ACE2 with 19-fold higher affinity than Victoria RBD, and neutralization titers are reduced 13.3-fold in convalescent plasma, 7.6-fold after Pfizer-BioNTech vaccination, and 9-fold after Oxford-AstraZeneca vaccination.

Key findings

  • Among 20 potent human mAbs, 14 had >10-fold loss of neutralization against B.1.351, with most showing complete knockout; the single anti-NTD mAb tested, 159, was also knocked out, consistent with the B.1.351 NTD deletion 242–244.
  • Convalescent plasma from early first-wave infection (n = 34) showed a 13.3-fold geometric mean reduction in FRNT50 against B.1.351 versus Victoria (p < 0.0001); the Results state 18 of 34 failed to reach 50% neutralization at 1:20, while the Discussion states 14 of 34.
  • Vaccinee sera showed reduced B.1.351 neutralization: Pfizer-BioNTech (n = 25) had 7.6-fold lower geometric mean titers (p < 0.0001), and Oxford-AstraZeneca (n = 25) had 9-fold lower titers (p < 0.0001); 9/25 AstraZeneca samples versus 2/25 Pfizer samples failed to reach 50% FRNT against B.1.351.
  • B.1.351 RBD bound ACE2 with KD 4.0 nM, 19-fold higher affinity than Victoria RBD and 2.7-fold higher than B.1.1.7 RBD; REGN10933 neutralization was 773-fold impaired, while REGN10987 and the AstraZeneca mAb pair were little affected.

Methods

  • Structure-function analysis comparing B.1.351 to the early Victoria isolate using focus reduction neutralization tests (FRNT) with convalescent plasma, B.1.1.7 patient plasma, Pfizer-BioNTech and Oxford-AstraZeneca vaccinee sera, a panel of 377 human mAbs from which the 20 most potent were selected, and clinical-stage mAb pairs.
  • Samples included early convalescent plasma (n = 34), B.1.1.7-infected patient plasma (n = 13), Pfizer-BioNTech vaccinee serum (n = 25), and Oxford-AstraZeneca vaccinee serum (n = 25).
  • Biolayer interferometry measured ACE2 and mAb binding to Victoria and B.1.351 RBDs; structural modeling and Fab/RBD complex analysis rationalized escape; statistics used Wilcoxon matched-pairs signed rank tests with two-tailed p values and geometric means, with FRNT IC50 determined by probit in SPSS.

Limitations

  • Stated: vaccine and convalescent samples were taken early and titers may rise further, but titers may also wane; it remains unknown how B.1.351-infected sera neutralize early Wuhan-related strains or variants B.1.1.7 and P.1; future studies should define mAbs from E484K-infected individuals; and it is important to determine whether vaccination or natural infection with early strains still protects against severe disease and hospitalization.
  • Evident from the text: the study reports in vitro neutralization and binding data, not clinical efficacy or protection outcomes; sample sizes are modest; and the paper itself contains a discrepancy between the Results and Discussion on how many convalescent samples failed to reach 50% neutralization at 1:20.

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

Integrity signals

Registry

Crossref · 10.1016/j.cell.2021.02.037

Cites

Statistics

Nothing to recompute.

Claims the paper makes

0 of 23 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    In the evolution of B.1.1.7 and B.1.351, NTD-deletion-only mutants and N501Y-only mutants were observed preceding the rising dominance of strains harboring both deletions and 501Y.

    “In the evolution of both the B.1.1.7 variant in the UK and the B.1.351 variant in South Africa, a substantial population of N-terminal domain (NTD)-deletion-only mutants (Δ69–70 in B.1.1.7 and Δ242–244 in B.1.153), and N501Y-only mutants were observed in both countries preceding the rising dominance of strains harboring both deletions and 501Y (Figures 1A and 1B).”
    Quote in the paperNot a substantial claim
  • Findingown data

    Pfizer-BioNTech vaccine serum induced 3.6-fold higher neutralization titers against Victoria than Oxford-AstraZeneca vaccine (p<0.0001).

    “The Pfizer-BioNTech vaccine serum induced 3.6-fold higher neutralization titers against the Victoria strain than the Oxford-AstraZeneca vaccine (p < 0.0001).”
    Quote in the paperNot a substantial claim
  • Findingown data

    A number of potent mAbs were able to potently neutralize B.1.351, including 222, 318, 253/55, 353/165, the AstraZeneca pair AZD1061 and AZD889, and Regeneron REGN10987.

    “Although the majority of potent mAbs suffered substantial reduction or knockout of activity, a number were able to potently neutralize B.1.351, including 222, 318, 253/55, and 353/165, the AstraZeneca pair AZD1061 and AZD889, and Regeneron REGN10987, which does not contact any of the mutation sites, whereas REGN10933 contacts both 417 and 484 and binding is abrogated.”
    Quote in the paperSubstantial claim
  • Findingown data

    18 of 34 early convalescent plasma samples failed to reach 50% neutralization of B.1.351 at a plasma dilution of 1:20.

    “Significantly, 18 of 34 samples failed to reach 50% neutralization at a plasma dilution of 1:20, with a number showing a near total reduction of neutralization activity.”
    Quote in the paperSubstantial claim
  • Findingown data

    For Oxford-AstraZeneca vaccine serum (n=25), geometric mean B.1.351 neutralization titers were 9-fold lower than for Victoria (p<0.0001).

    “For the Oxford-AstraZeneca vaccine serum, geometric mean B.1.351 titers were 9-fold lower than for Victoria (p < 0.0001) (Figure 3D; Table S2).”
    Quote in the paperSubstantial claim
  • May combine two claims. 28
  • Classified as probably not a substantial claim. 14
  • The quote only partly states this claim. 1

  • May combine two claims.

    Findingown data

    Neutralization of REGN10987 was unaffected by B.1.351, while REGN10933 was severely impaired (773-fold).

    “The neutralization of REGN10987 was unaffected by B.1.351, while REGN10933 was severely impaired (773-fold) (Figure 4B; Table S2).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The KD for binding of soluble ACE2 to B.1.351 RBD is 4.0 nM, with Kon 4.78E4/Ms and Koff 1.93E−4/s.

    “The KD is 4.0 nM, Kon is 4.78E4/Ms, and Koff is 1.93E−4/s; thus, the off-rate is approximately 1.5 h.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Chimeras 253H/55L and 253H/165L can both neutralize B.1.351, with FRNT50 titers of 9 and 13 ng/mL, respectively.

    “The chimeras 253H/55L and 253H/165L can both neutralize B.1.351, with FRNT50 titers of 9 and 13 ng/mL, respectively.”
    Quote in the paperSubstantial claim

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

    Findingown data

    B.1.1.7 and B.1.351 quickly became overwhelmingly dominant in the UK and South Africa, respectively.

    “It appears that B.1.1.7 and B.1.351 quickly became overwhelmingly dominant in the UK and South Africa, respectively.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingnone given

    Despite changes in B.1.351, residual neutralizing capacity is present in many convalescent and vaccine sera, with some individuals showing minimal reduction of titers relative to Victoria.

    “Despite the changes in B.1.351, residual neutralizing capacity is present in many convalescent and vaccine sera, with some individuals showing minimal reduction of titers relative to the Victoria strain.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Neutralization of B.1.351 by sera from naturally infected or vaccinated individuals is significantly reduced, leading in some cases to a complete inability to neutralize B.1.351 virus.

    “Neutralization of B.1.351 by sera from naturally infected or vaccinated individuals is significantly reduced, leading in some cases to a complete inability to neutralize B.1.351 virus.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    FRNT50 titers for mAbs 55, 165, 253, and 318 were relatively equal between Victoria and B.1.351, indicating their epitopes are not perturbed by K417N, E484K, and N501Y mutations.

    “The FRNT50 titers for mAbs 55, 165, 253, and 318 were also relatively equal between Victoria and B.1.351, indicating that their epitopes are not perturbed by the K417N, E484K, and N501Y mutations.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    For Fabs tested against B.1.351, only 4 (or 2 if engineered LC versions of 253 are removed) had KDs below 4 nM, compared with 17 against Victoria, and 7 Fabs failed to achieve near-micromolar affinity.

    “whereas for the antigen binding fragments (Fabs) tested against Victoria, 17 had KDs below 4 nM (the affinity of ACE2 for B.1.351) against B.1.351, this reduced to 4 (or 2 if the engineered light-chain [LC] versions of 253 are removed [(Dejnirattisai et al., 2021)]), with 7 Fabs failing to achieve near-micromolar affinity.”
    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.

    Findingown data

    As of February 2, 2021, in COG-UK, 21 B.1.1.7 sequences had independently acquired 484K (but not 417N), and 90 sequences displayed these mutations in the background of B.1.351.

    “as of February 2, 2021, in the COG-UK database, 21 of the B.1.1.7 sequences were observed to have independently acquired the 484K (but not the 417N) mutation found in the B.1.351 variant, and 90 sequences display these mutations in the background of B.1.351 (as defined by bearing the characteristic Δ242–244 NTD deletion).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    REGN10933 contacts both 417 and 484 and its binding is abrogated by B.1.351.

    “Although the majority of potent mAbs suffered substantial reduction or knockout of activity, a number were able to potently neutralize B.1.351, including 222, 318, 253/55, and 353/165, the AstraZeneca pair AZD1061 and AZD889, and Regeneron REGN10987, which does not contact any of the mutation sites, whereas REGN10933 contacts both 417 and 484 and binding is abrogated.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Among 20 potent mAbs tested, 14 had >10-fold fall in neutralization titers against B.1.351, with most showing complete knockout.

    “The effects on mAb neutralization were severe, 14 of 20 antibodies had >10-fold fall in neutralization titers, with most of these showing a complete knockout of activity.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Structures of 253 and chimera Fabs with RBD or spike show they bind almost identically to the same epitope and do not contact any of the three mutation site residues.

    “Structures of 253 and these chimera Fabs with either RBD or spike show that they bind almost identically to the same epitope and do not contact any of the three mutation site residues, correlating well with the neutralization and BLI binding data (Figure 5C).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    The affinity of B.1.351 RBD for soluble ACE2 is 19-fold higher than for Victoria RBD and 2.7-fold higher than for B.1.1.7 RBD.

    “As expected, the affinity for B.1.351 RBD is high; in fact, it is 19-fold higher than for the Victoria RBD and 2.7-fold higher than for B.1.1.7 ((Dejnirattisai et al., 2021); Supasa et al., 2021).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Dejnirattisai et al., 2021 source

      Not checked in the free run.

    • cites Supasa et al., 2021 source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    Four of the five IGHV3-53 antibodies tested (150, 158, 175, 269) had neutralization and binding severely compromised or abolished against B.1.351, while mAb 222 was unaffected.

    “Four of these, 150, 158, 175, and 269, have their neutralization and binding abilities severely compromised or abolished, while 222 is an exception, since its binding is unaffected by the B.1.351 variant (Figures 6F and 6G).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The B.1.351 strain used in this report has 8 changes relative to the Wuhan sequence and lacks L18F and R246I compared with the Tegally et al. (2021) isolate.

    “Sequencing of the strain used in this report, from a case in the UK, shows only 8 changes and lacks L18F and R246I compared with the Tegally et al. (2021) isolate.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Tegally et al. (2021) source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Premisenone given

    All three recently identified variant SARS-CoV-2 strains have acquired mutations in the ACE2 interaction surface of the RBD: N501Y in B.1.1.7; K417N, E484K, and N501Y in B.1.351; and K417T, E484K, and N501Y in P.1.

    “All three recently identified variant SARS-CoV-2 strains have acquired mutations in the ACE2 interaction surface of the RBD: N501Y in B.1.1.7; K417N, E484K, and N501Y in B.1.351; and K417T, E484K, and N501Y in P.1.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Yeast display of libraries of RBD mutants has been used to select variants for escape from binding to immune serum or for increased affinity of binding to ACE2.

    “Alternatively, yeast display of libraries of RBD mutants has been used to select variants for escape from binding to immune serum or alternatively for increased affinity of binding to the ACE2 receptor (Zahradník et al., 2021).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Zahradník et al., 2021

      Not checked in the free run.

  • May combine two claims. The quote only partly states this claim.

    Premisenone given

    The ACE2-binding site extends across the neck and both shoulders of the RBD; N501Y is on the right shoulder, K417N at the back of the neck, and E484K on the left shoulder.

    “In this context, the ACE2-binding site extends across the neck and both shoulders. N501Y is on the right shoulder, K417N at the back of the neck, and E484R on the left shoulder.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    The change of charge at E484 from negative to positive and shortening of residue 417 side chain from K to N would abolish interactions in Fab 88, explaining the several hundred-fold loss in KD.

    “The change of charge at E484 from negative to positive and shortening of the residue 417 side chain from K to N would be expected to abolish all these interactions, explaining the several hundred-fold loss in KD.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    The RBD is contained in the S1 subunit of spike and is responsible for interacting with ACE2.

    “The RBD is contained in the S1 subunit of spike and is responsible for interacting with the SARS-CoV-2 cellular receptor angiotensin-converting enzyme-2 (ACE2) (Hoffmann et al., 2020).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Hoffmann 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

    All three variants may lead to increased transmissibility, with good evidence for this with B.1.1.7 in the UK.

    “All three variants may lead to increased transmissibility, with good evidence for this with B.1.1.7 in the UK.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: In vitro ACE2 binding affinity reflects viral transmissibility or fitness.

  • May combine two claims.

    Interpretationreasoning

    The 242-244 deletion in B.1.351 NTD will alter presentation of RBD loop 246-253, compromising binding to mAbs 159 and 4A8.

    “The 242–244 deletion will undoubtedly alter the presentation of this loop, compromising binding to these mAbs.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    The 242-244 deletion in B.1.351 will disrupt the binding sites of neutralizing anti-NTD antibodies, as shown by failure of neutralization of anti-NTD mAb 159.

    “The second theme is deletions in the NTD: 69–70 and 144 in B.1.1.7 and 242–244 in B.1.351, both of which will disrupt the binding sites of neutralizing anti-NTD antibodies, as shown here by the failure of neutralization of anti-NTD mAb 159.”
    Quote in the paperSubstantial claim

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

    Interpretationnone given

    The use of mAb therapy or prophylaxis, particularly for extended periods in chronically infected immunocompromised individuals, is likely to drive the emergence of resistance mutations.

    “However, it must be recognized that the use of mAb therapy or prophylaxis, particularly for extended periods in chronically infected immunocompromised individuals, is likely to drive the emergence of resistance mutations.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    mAb 222 possesses the IGHV3-53 V-region and maintains potency against B.1.1.7 and B.1.351 due to a slight change in HC CDR3 length and suitable LC choice.

    “While all other IGHV3-53 antibodies are severely compromised in binding B.1.351, a slight change in the length of the HC CDR3 and a suitable choice of LC enable mAb 222 to maintain potency against B.1.1.7 and B.1.351.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    The Novavax vaccine achieved 95.6% efficacy against previous SARS-CoV-2 strains and 85.6% against B.1.1.7 in the UK.

    “Very recent data suggest that the Novavax vaccine, which achieved 95.6% efficacy against previous SARS-CoV-2 strains and 85.6% against B.1.1.7 in the UK”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites https://www.novavax.com/sites/default/files/2021-02/20210202-NYAS-Novavax-Final.pdf

      Not checked in the free run.

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

    Study design and conductnone given

    The vaccine and convalescent samples used in the neutralization studies were taken early.

    “The vaccine and convalescent samples used in the neutralization studies in this report were taken early”
    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

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

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

  • Classified as probably not a substantial claim.

    Study design and conductown data

    The construct used encodes exactly the same protein as native RBD except the K417N, E484K and N501Y mutations, as confirmed by sequencing.

    “This construct encodes exactly the same protein as native RBD except the K417N, E484K and N501Y mutations, as confirmed by sequencing.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Both the Oxford-AstraZeneca and Pfizer vaccines give substantial initial efficacy after a single dose against parental strains (~76 and 89%, respectively).

    “However, both the Oxford-AstraZeneca and Pfizer vaccines give substantial initial efficacy after a single dose of vaccine against parental strains (∼76 and 89%, respectively)”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Baden et al., 2021 source

      Not checked in the free run.

    • cites Polack et al., 2020 source

      Not checked in the free run.

    • cites Voysey et al., 2021b

      Not checked in the free run.

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

    Interpretationreasoning

    Viruses carrying the E484K and N501Y mutations likely have increased transmissibility.

    “which is compatible with the observation that viruses carrying the E484K and N501Y mutations likely have increased transmissibility.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: N501Y is found in all B.1.1.7, B.1.351, and P.1 lineages and E484K is found in B.1.351 and P.1.

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

    Interpretationreasoning

    As population immunity increases due to vaccination and natural infection, the evolutionary pressure for viral variants to be selected ratchets up.

    “as population immunity increases due to vaccination and natural infection, the evolutionary pressure for viral variants to be selected ratchets up.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    In vitro evolution can generate ultra-high-affinity RBD variants for ACE2 in the sub-picomolar range, a higher affinity than almost all mAbs described to date.

    “The ability to generate ultra-high-affinity RBD variants for ACE2 in the sub-picomolar range by in vitro evolution (Zahradník et al., 2021), a higher affinity than almost all mAbs described to date”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Zahradník et al., 2021

      Not checked in the free run.

33 of 33

  • The paper relies on this without support.

    Neutralization titer is a proxy for protection against SARS-CoV-2 infection or disease.

    “In a number of cases, it would appear that convalescent and some vaccine serum offers limited protection against this variant.”
    “Neutralization of B.1.351 by sera from naturally infected or vaccinated individuals is significantly reduced, leading in some cases to a complete inability to neutralize B.1.351 virus.”

  • The paper relies on this without support.

    Blocking RBD-ACE2 interaction plays a major role in natural and vaccine-induced protection from SARS-CoV-2 infection.

    “Blocking RBD-ACE2 interaction is thought to play a major role in natural and vaccine-induced protection from SARS-CoV-2 infection.”

  • The paper relies on this without support.

    The B.1.351 strain used in this report is representative of circulating B.1.351 variants.

    “Sequencing of the strain used in this report, from a case in the UK, shows only 8 changes and lacks L18F and R246I compared with the Tegally et al. (2021) isolate.”

  • The paper relies on this without support.

    In vitro ACE2 binding affinity reflects viral transmissibility or fitness.

    “like the increased receptor binding and potential increased transmissibility imparted by the RBD mutations”

  • The paper relies on this without support.

    N501Y is found in all B.1.1.7, B.1.351, and P.1 lineages and E484K is found in B.1.351 and P.1.

    “Principal among these are N501Y found in all B.1.1.7, B.1.351, and P.1 lineages and E484K found in B.1.351 and P.1.”

  • The paper relies on this without support.

    All approaches to select RBD mutants have led to identification of a common set of mutations found in circulating variant viruses.

    “Of great interest is that all of these approaches have led to the identification of a common set of mutations found in the variant viruses that are now circulating.”

  • The paper relies on this without support.

    The Janssen single-dose COVID-19 vaccine showed 72% efficacy at preventing moderate and severe disease, reduced to 57% in South Africa.

    “The Janssen single-dose COVID-19 vaccine showed 72% efficacy at preventing moderate and severe disease, which was reduced to 57% in South Africa.”

  • The paper relies on this without support.

    In South Africa, rates of previous infection are relatively high (estimate >30%).

    “where the rates of previous infection are relatively high (estimate >30%)”
8 of 8

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 [31]

  • Recent studies have consistently reported lower neutralizing antibody titers against B.1.351 after vaccination but not against B.1.1.7.

    “Concerning neutralization of VOCs, recent studies have consistently reported lower neutralizing antibody titers against B.1.351 after vaccination but not against B.1.1.7 (39, 42, 48–59).”

    From SARS-CoV-2 variants of concern partially escape humoral but not T cell responses in COVID-19 convalescent donors and vaccine recipients (2021) · cites this paper as [51]

  • Several studies have shown reduced vaccine efficacy against mild to moderate COVID-19 in countries where B.1.351 was dominant, although protection against severe disease appears preserved.

    “Several studies have now shown that there is reduced vaccine efficacy against mild to moderate disease in countries where B1.351 was dominant (Zhou et al., 2021; Shinde et al., 2021; Madhi et al., 2021, Vaccines and Related Biological Products Advisory Committee, 2021), although protection against severe disease appears to be preserved.”

    From Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum (2021) · cites this paper as Zhou et al., 2021

  • The neutralizing titers of convalescent and vaccine sera are reduced to B.1.351, leading to a 13-fold reduction in neutralizing titers of convalescent serum, with a number of neutralizing mAbs losing activity completely.

    “The neutralizing titers of convalescent and vaccine sera are reduced to the variants with B.1.351 of most concern, leading to a 13-fold reduction in neutralizing titers of convalescent serum, with a number of neutralizing monoclonal antibodies losing activity completely (Zhou et al., 2021; Supasa et al., 2021; Dejnirattisai et al., 2021b; Shinde et al., 2021; Madhi et al., 2021; Food and Drug Adm”

    From Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum (2021) · cites this paper as Zhou et al., 2021

  • The Beta variant is associated with reduced susceptibility to many mAbs because E484K interferes with binding of several RBM class 1 and 2 mAbs and K417N interferes with the binding of several RBM class 1 mAbs.

    “The Beta variant is associated with reduced susceptibility to many mAbs because E484K interferes with binding of several RBM class 1 and 2 mAbs and K417N interferes with the binding of several RBM class 1 mAbs 104,117,121,163,217 .”

    From The biological and clinical significance of emerging SARS-CoV-2 variants (2021) · cites this paper as [104]

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.

  • B.1.351 E484 mutation is identified as both R and K

    Minor

    The binding analysis calls the characteristic mutation E484R, whereas the sequenced study virus and the rest of the paper identify it as E484K.

  • AstraZeneca antibody identifier differs from the resources table

    Minor

    The clinical-antibody Results name AZD106, but the resources table identifies the antibody as AZD1061.

  • Pfizer serum collection window differs between Results and Methods

    Minor

    The Results give a window of 4-17 days after the second dose; the figure caption and Methods give 7-17 days.

  • A loop described as RBD is shown as part of the NTD

    Minor

    The text calls residues 246-253 an RBD loop, but the accompanying figure caption locates the antibody-binding region and nearby deletion in the spike NTD.

  • Conflicting counts of convalescent samples that failed neutralization

    Minor

    The Results say 18 of 34 samples failed to reach 50% neutralization at 1:20, while the Discussion says 14 of 34 failed at the same dilution.

  • Figure 1 gives a different position for the B.1.351 NTD deletion

    Minor

    The Figure 1 caption twice identifies the South African deletion as 241-243, while the sequenced study virus is reported to have deletion 242-244.

6 of 6

No citation lists for this paper

No citation lists for this paper yet — checked again daily.

References 38 · Cited by 992

Research works printed but not linked: 1

  1. Faria, 2021, Genomic characterisation of an emergent SARS-CoV-2 lineage in Manaus: preliminary findings - SARS-CoV-2 coronavirus / nCoV-2019 Genomic Epidemiology - Virological, virological.org

Authors
Zhou, D., Dejnirattisai, W., Supasa, P., Liu, C., Mentzer, A. J., Ginn, H. M., Zhao, Y., Duyvesteyn, H. M. E., Tuekprakhon, A., Nutalai, R., Wang, B., Paesen, G. C., Lopez-Camacho, C., Slon-Campos, J., Hallis, B., Coombes, N., Bewley, K., Charlton, S., Walter, T. S., Skelly, D., Lumley, S. F., 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., James, W., Carroll, M. W., Klenerman, P., Barnes, E., Dunachie, S. J., Fry, E. E., Mongkolsapaya, J., Ren, J., Stuart, D. I., & Screaton, G. R.
Affiliations
  • Centre for Human Genetics (GB)
  • Instruct-ERIC (GB)
  • Public Health England (GB)
  • 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
2021-04
Volume
184
Issue
9
Pages
2348-2361.e6
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2021.02.037
PMC
PMC7901269
OpenAlex
W3131995220
Cited by
992
References
38
Citations by year
2026: 20 · 2025: 27 · 2024: 55 · 2023: 129 · 2022: 366 · 2021: 393 · 2020: 1
FWCI
74.98
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Greater South Information System
Funders
  • UK Research and Innovation
  • Medical Research Council (ACE2, MR/N00065X/1, 203141/Z/16/Z, 095541/A/11/Z, 090532/Z/09/Z)
  • Public Health England
  • National Institute for Health Research
  • Department of Health and Social Care
  • NIHR Oxford Biomedical Research Centre
  • National Institutes of Health (U19 I082360, WT204969/Z/16/Z)
  • Wellcome Trust (101122/Z/13/Z)
  • Cancer Research UK (C375/A17721)
  • Coalition for Epidemic Preparedness Innovations
  • Chinese Academy of Medical Sciences
  • China Academy of Chinese Medical Sciences (2018-I2M-2-002)
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, B.1.351 variant, immune evasion, spike protein mutations, receptor binding domain, E484K, K417N, N501Y, ACE2 binding, monoclonal antibody neutralization, vaccine-induced immunity, convalescent serum, COVID-19 vaccines, structure-function analysis
MeSH terms
COVID-19, SARS-CoV-2, COVID-19 Vaccines, COVID-19 Serotherapy, Animals, Antibodies, Monoclonal, Chlorocebus aethiops, Clinical Trials as Topic, Humans, Immunization, Passive, Models, Molecular, Mutation, Neutralization Tests, Protein Binding, Vero Cells, HEK293 Cells

About these checks

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.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-06.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-06.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review