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Cited by 529SARS-CoV-2 and COVID-19 Researchvaccines and immunoinformatics approachesCOVID-19 Clinical Research Studies

SARS-CoV-2 variants of concern partially escape humoral but not T cell responses in COVID-19 convalescent donors and vaccine recipients

Open access
Geers, Daryl, Shamier, Marc C., Bogers, Susanne, den Hartog, Gerco, Gommers, Lennert, Nieuwkoop, Nella N., Schmitz, Katharina S., Rijsbergen, Laurine C. +17 more·2021·Science Immunology
DOI 10.1126/sciimmunol.abj1750PMC PMC9268159
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Abstract

Infection- or vaccination-induced SARS-CoV-2 S–specific CD4 + T cells are indifferent to the S mutations of variants of concern.

AI snapshot

Written from the paper’s full text.

TL;DR

In a prospective cohort of 121 BNT162b2-vaccinated health care workers, prior COVID-19 led to rapid recall after one dose, while COVID-19–naive donors required two doses for comparable humoral responses. B.1.351 partially escaped neutralizing and Fc-mediated antibody responses, but CD4+ T cell responses to WT, B.1.1.7, and B.1.351 S proteins were comparable.

Key findings

  • Among 121 HCWs (23 COVID-19–recovered, 98 naive), one vaccine dose boosted binding antibodies in all recovered donors; in naive donors, 92.5% had detectable anti-RBD Ig after one dose but only 53.2% had OD ratio >10, rising after dose two to all detectable and 93.3% with ratio >10. S1 IgG by MIA rose from geometric mean 252.6 ± 49.55 to 2088.5 ± 287.5 BAU/ml in naive donors after the second dose (P < 0.0001).
  • Neutralizing antibodies against WT were detected in all 13 recovered donors before vaccination; one dose boosted PRNT50 to a geometric mean plateau of 1:1874. Naive donors reached a lower peak after two doses (geometric mean titer 1:189, P < 0.0001 vs recovered). Against B.1.351, titers were consistently lower: 2.7-fold and 3.3-fold decreases post-vaccinations 1 and 2 in recovered donors, and a 3.1-fold decrease after dose two in naive donors; B.1.1.7 titers were higher (2.5-fold and 2.2-fold increases in recovered donors).
  • S-specific ADCC-mediating antibodies were induced by infection and vaccination, with comparable activity against WT and B.1.1.7 S, but significantly reduced activity against B.1.351 S at almost all time points in both naive and recovered donors.
  • CD4+ T cell responses did not differ between WT S and B.1.1.7 S or WT S and B.1.351 S. In naive donors, 5 of 7 were CD4+ T cell responders after one or two vaccinations; in recovered donors, 8 of 12 responded before vaccination and 10 of 12 after one or two vaccinations. CD8+ S-specific responses were difficult to detect and were not used to draw conclusions on VOC cross-reactivity.

Methods

  • Prospective cohort of 121 symptomatic HCWs in the Netherlands enrolled from April 2020; 98 classified COVID-19–naive and 23 COVID-19–recovered by RT-PCR and serology. All received two BNT162b2 mRNA doses 21 days apart. Binding antibody assays were performed on all 121; in-depth humoral analyses on 25 (13 recovered, 12 naive); T cell analyses on 20 (13 recovered, 7 naive).
  • Humoral assays included Wantai RBD total Ig ELISA, Luminex S1 IgG MIA, in-house N/S ELISA, and PRNT50 using infectious WT SARS-CoV-2 (D614G), B.1.1.7, and B.1.351. ADCC was measured by NK92.05-CD16 degranulation (CD107a) against WT N, WT S, B.1.1.7 S, and B.1.351 S.
  • T cell responses were measured by AIM flow cytometry (CD69/CD137 in CD4+ and CD8+ subsets) after stimulation with overlapping WT S peptide pools or peptide pools covering mutated regions of B.1.1.7 and B.1.351, with IFN-γ ELISA in a subset. Statistical analyses used GraphPad Prism 9.0.2.

Limitations

  • The paper states the study population was selected HCWs, relatively young, predominantly female, and with mild COVID-19 if previously infected; it was underpowered to compare age groups or comorbidities.
  • The paper states in-depth T cell profiling was limited to 20 donors, focused only on S-specific T cells, and could not further address CD8+ T cell responses to VOCs because of low SARS-CoV-2–specific CD8+ T cell frequency; peptide pools of 15-mers may have limited sensitivity, and some pre-exposure S-specific T cells were probably cross-reactive with seasonal human coronaviruses.
  • The paper states it did not analyze the P.1 VOC, and future studies are needed to assess whether neutralizing antibody differences correlate with breakthrough infection risk and whether ADCC should be measured with infectious virus and primary cells. Evident from the text: the study reports immune responses, not clinical protection or breakthrough infection outcomes.

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

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Registry

Crossref · 10.1126/sciimmunol.abj1750

Cites

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Statistics

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Claims the paper makes

0 of 40 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Percentages of degranulating NK cells were comparable between WT and B.1.1.7 S at all time points, regardless of prior SARS-CoV-2 exposure or number of vaccinations.

    “Percentages of degranulating NK cells were comparable between WT and B.1.1.7 S at all time points, regardless of whether donors had been previously exposed to SARS-CoV-2 or not, and the number of vaccinations.”
    Quote in the paperNot a substantial claim
  • Findingown data

    In both COVID-19-naive and -recovered donors and at all time points assessed, sera had reduced binding affinity for the B.1.351 S protein when compared with the WT S protein.

    “In both COVID-19–naive and –recovered donors and at all time points assessed, sera had reduced binding affinity for the B.1.351 S protein when compared with the WT S protein.”
    Quote in the paperSubstantial claim
  • Findingown data

    A nonsignificant trend for increasing CD8+ T cell responses was observed after vaccination of COVID-19-negative donors.

    “A nonsignificant trend for increasing CD8+ T cell responses (both AIM and SI, Fig. 4D; data at T0 from COVID-19–recovered donors lacking due to low counts in CD8+ gate) was observed after vaccination of COVID-19–negative donors.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Neutralizing antibodies against WT SARS-CoV-2 (which contained the D614G mutation) were detected in all sera collected from 13 COVID-19-recovered HCWs before vaccination.

    “Neutralizing antibodies against WT SARS-CoV-2 (which contained the D614G mutation) were detected in all sera collected from N = 13 COVID-19–recovered HCWs before vaccination.”
    Quote in the paperNot a substantial claim
  • Findingown data

    In COVID-19-naive donors, WT S-specific CD4+ T cells expressing AIM (CD69+CD137+) were detected after the first and second vaccination.

    “In COVID-19–naive donors, WT S–specific CD4+ T cells expressing AIM (CD69+CD137+) were detected after the first and second vaccination (Fig. 4B, T3 to Vx13, P = 0.0374; T3 to Vx23, P = 0.0016, Kruskal-Wallis test).”
    Quote in the paperNot a substantial claim
  • May combine two claims. 30
  • Classified as probably not a substantial claim. 28
  • The quote only partly states this claim. 1

  • May combine two claims.

    Findingown data

    In COVID-19-recovered donors, 8 of 12 CD4+ T cell responders were identified before vaccination, which increased to 10 of 12 responders after one or two vaccinations.

    “In COVID-19–recovered donors, 8 of 12 responders were identified before vaccination, which increased to 10 of 12 responders after one or two vaccinations.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Percentages of CD107a+ NK cells were significantly correlated to binding antibody titers, but the correlation was not evident at all time points assessed separately.

    “Percentages of CD107a+ NK cells were significantly correlated to the binding antibody titers (shown in Fig. 2D); however, the correlation was not evident at all time points assessed separately (fig. S2).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Neutralizing antibodies were detected after one vaccination in 7 of 12, 6 of 12, and 2 of 12 COVID-19-naive donors against WT SARS-CoV-2, B.1.1.7, and B.1.351, respectively; a second vaccine dose boosted that to 12 of 12, 11 of 12, and 10 of 12.

    “Neutralizing antibodies were detected after one vaccination in 7 of 12, 6 of 12, and 2 of 12 COVID-19–naive donors against WT SARS-CoV-2, B.1.1.7, and B.1.351, respectively. A second vaccine dose boosted that to 12 of 12, 11 of 12, and 10 of 12.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In COVID-19-recovered donors, S-specific CD4+ T cells were already detected in the convalescent phase, were boosted after the first vaccination, and a second vaccination did not lead to additional boosting.

    “In COVID-19–recovered donors, S-specific CD4+ T cells were already detected in the convalescent phase, which were boosted after the first vaccination. A second vaccination did not lead to an additional boosting effect (Fig. 4B).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In prevaccination sera from COVID-19-recovered donors, neutralizing antibodies against WT SARS-CoV-2 (D614G), B.1.1.7, and B.1.351 were detected in 13 of 13, 12 of 13, and 7 of 13 donors, respectively.

    “In prevaccination sera from COVID-19–recovered donors, neutralizing antibodies against WT SARS-CoV-2 (D614G), B.1.1.7, and B.1.351 were detected in 13 of 13, 12 of 13, and 7 of 13 donors, respectively (table S1).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In COVID-19-naive donors, CD4+ T cell responders were not observed before vaccination, whereas five of seven responders were identified after one or two vaccinations.

    “In COVID-19–naive donors, CD4+ T cell responders were not observed before vaccination, whereas five of seven responders were identified after one or two vaccinations.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    S-specific antibodies were absent before vaccination in the COVID-19-naive cohort, whereas S-specific antibodies were detected before vaccination in 22 of 23 COVID-19-recovered donors.

    “The absence of S-specific antibodies before vaccination was confirmed by both assays in the COVID-19–naive cohort, whereas S-specific antibodies were detected before vaccination in 22 of 23 COVID-19–recovered donors [optical density (OD) ratio >1 in Wantai ELISA and binding antibody units (BAU)/ml >10.08 in MIA].”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing), S4 (based). The quote only partly states this claim.

    Findingown data

    In MIA, all COVID-19-naive participants had detectable antibodies after one vaccination.

    “In MIA, all participants had detectable antibodies after one vaccination (Fig. 2C and table S1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In COVID-19-naive participants, 92.5% had detectable total anti-RBD Ig after one vaccine dose, but only 53.2% had an OD ratio >10.

    “In COVID-19–naive participants, 92.5% had detectable total anti-RBD Ig after one vaccine dose, but only 53.2% had an OD ratio >10 (Fig. 2B).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    A single vaccination boosted PRNT50 titers in COVID-19-recovered HCWs to a geometric mean plateau value of 1:1874; titers did not increase further after a second vaccination.

    “A single vaccination boosted the PRNT50 titers to a geometric mean plateau value of 1:1874 [P < 0.0001, repeated measures (RM) one-way analysis of variance (ANOVA)]. Titers did not increase further after a second vaccination.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    N-specific antibodies were not detected in 11 of 12 COVID-19-naive donors, whereas substantial levels of N-specific antibodies were detected in 12 of 13 COVID-19-recovered donors.

    “N-specific antibodies were not detected in 11 of 12 COVID-19–naive donors (1 low positive), whereas substantial levels of N-specific antibodies were detected in 12 of 13 COVID-19–recovered donors.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    A clear boosting effect after the second vaccination was observed in COVID-19-naive donors: all participants then had detectable antibodies, 93.3% had a ratio >10 in ELISA, and significantly higher levels of S1-specific IgG were observed in MIA.

    “A clear boosting effect after the second vaccination was observed in COVID-19–naive donors. All participants then had detectable antibodies, and 93.3% had a ratio >10 in ELISA, and significantly higher levels of S1-specific IgG were observed in MIA (geometric mean 252.6 ± 49.55 to 2088.5 ± 287.5 BAU/ml, P < 0.0001, Friedman test).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    A second vaccination of COVID-19-recovered participants did not further boost S1-specific IgG antibodies; a plateau was reached after a single shot.

    “The quantitatively interpretable MIA also showed that a second vaccination of COVID-19–recovered participants did not further boost S1-specific IgG antibodies; a plateau was reached after a single shot.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    After one vaccination, all COVID-19-recovered participants showed a surge in antibody levels with OD ratios >10 detected by ELISA, confirmed by MIA.

    “After one vaccination, all COVID-19–recovered participants showed a surge in antibody levels with OD ratios >10 detected by ELISA (Fig. 2B, P < 0.0001, Friedman test).”
    • Also stated in: § Rapid boosting of S-specific antibodies in COVID-19–recovered donors · plain
      “This increase was confirmed by MIA (Fig. 2C, P = 0.0001, Friedman test; table S1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In COVID-19-recovered donors, ADCC-mediating antibodies were already boosted by a single vaccination to peak levels, and the second shot did not lead to additional boosting.

    “In COVID-19–recovered donors, ADCC-mediating antibodies were already boosted by a single vaccination to peak levels, and the second shot did not lead to an additional boosting (reminiscent of binding and neutralizing antibodies; see Fig. 2).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    PRNT50 values were boosted by a second vaccination to detectable levels in all COVID-19-naive donors, but the peak titer was significantly lower compared with COVID-19-recovered participants (geometric mean titer 1:189).

    “PRNT50 values were boosted by a second vaccination to detectable levels in all donors (P = 0.0005, Wilcoxon test; table S1), but the peak titer was significantly lower compared with COVID-19–recovered participants (geometric mean titer 1:189, P < 0.0001, unpaired t test).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In COVID-19-naive donors, the first vaccination led to low-level detection of ADCC-mediating antibodies, which were further boosted by the second vaccination.

    “In COVID-19–naive donors, the first vaccination led to low-level detection of ADCC-mediating antibodies, which were further boosted by the second vaccination.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    At two time points, a slightly increased binding affinity for B.1.1.7 S was observed (Vx13 for naive donors and T3 for convalescent donors).

    “In addition, at two time points, a slightly increased binding affinity for B.1.1.7 S was observed (Vx13 for naive donors and T3 for convalescent donors).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    A single vaccination was sufficient to boost neutralizing antibodies to detectable levels for all SARS-CoV-2 variants, and a second dose did not further boost antibody titers.

    “A single vaccination was sufficient to boost neutralizing antibodies to detectable levels for all SARS-CoV-2 variants, and a second dose did not further boost antibody titers.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In COVID-19-naive donors, WT S-specific ADCC-mediating antibodies were not detected before vaccination, whereas in COVID-19-recovered donors, WT S-specific ADCC-mediating antibodies were detected in the convalescent phase.

    “In COVID-19–naive donors, WT S–specific ADCC-mediating antibodies were not detected before vaccination, whereas in COVID-19–recovered donors, WT S–specific ADCC-mediating antibodies were detected in the convalescent phase (Fig. 3C, P = 0.0038, RM one-way ANOVA; table S1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In some sera, increased binding to B.1.1.7 S by ELISA was observed, but not at all time points.

    “In some sera, we observed increased binding to B.1.1.7 S by ELISA as well, but not at all time points”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingreasoning

    The presence of antibodies in response to vaccination can be measured but not accurately quantified by the Wantai ELISA.

    “Because this sensitive assay is often used in diagnostic laboratories, we show here that the presence of antibodies in response to vaccination (in the absence or presence of preexisting SARS-CoV-2 immunity) can indeed be measured but not accurately quantified.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In COVID-19-recovered participants, CD8+ S-specific T cells were already observed in the convalescent phase, with increased levels after two vaccinations.

    “In COVID-19–recovered participants, CD8+ S–specific T cells were already observed in the convalescent phase, with increased levels after two vaccinations (P = 0.046, Wilcoxon rank test).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    With peptide pools covering mutated regions, S-specific CD4+ T cell responses were detected in post-vaccination samples from COVID-19-naive donors and in convalescent and post-vaccination samples of COVID-19-recovered donors, but not before vaccination in naive participants.

    “With these pools, S-specific CD4+ T cell responses were again detected (SI > 2) in the post-vaccination samples from COVID-19–naive samples and in the convalescent and post-vaccination samples of COVID-19–recovered donors (Fig. 4, E and F, shown as percentages of activated cells within the CD4+ T cell subset in fig. S4), but T cell responses were not observed before vaccination in the COVID-19–na”
    Quote in the paperSubstantial claim

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

    Findingcitation

    The Luminex MIA allowed clear interpretation and quantitative comparison of antibody responses within groups and at different time points.

    “The Luminex MIA, on the other hand, allowed clear interpretation and quantitative comparison of antibody responses within the groups and at different time points (45).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [45] G. den Hartog, R. M. Schepp, M. Kuijer, C. GeurtsvanKessel, J. van Beek, N. Rots, M. P. G. Koopmans, F. R. M. van der Klis, R. S. van Binnendijk, SARS-CoV-2-specific antibody detection for seroepidemiology: A multiplex analysis approach accounting for accurate seroprevalence. J. Infect. Dis. 222, 1452– 1461 (2020). 32766833 PMC7454740 source

      Not checked in the free run.

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

    Study design and conductown data

    No significant differences were observed in binding antibody data as determined by MIA between the total cohort and samples selected for in-depth analysis.

    “No significant differences were observed in binding antibody data as determined by MIA between the total cohort and samples selected for in-depth analysis (table S2).”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    In ex vivo studies, NK cells from patients with COVID-19 displayed impaired cytotoxicity.

    “In ex vivo studies, NK cells from patients with COVID-19 displayed impaired cytotoxicity (64, 65)”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [64] M. Zheng, Y. Gao, G. Wang, G. Song, S. Liu, D. Sun, Y. Xu, Z. Tian, Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cell. Mol. Immunol. 17, 533– 535 (2020). 32203188 PMC7091858 source

      Not checked in the free run.

    • cites [65] A. J. Wilk, A. Rustagi, N. Q. Zhao, J. Roque, G. J. Martinez-Colon, J. L. McKechnie, G. T. Ivison, T. Ranganath, R. Vergara, T. Hollis, L. J. Simpson, P. Grant, A. Subramanian, A. J. Rogers, C. A. Blish, A single-cell atlas of the peripheral immune response in patients with severe COVID-19. Nat. Med. 26, 1070– 1076 (2020). 32514174 PMC7382903 source

      Not checked in the free run.

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

    Premisecitation

    ADCC-mediating antibodies have been detected in plasma of COVID-19 convalescent donors.

    “ADCC-mediating antibodies have been detected in plasma of COVID-19 convalescent donors (16, 67, 68).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
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  • May combine two claims.

    Premisecitation

    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).”
    Quote in the paperNot a substantial claim0 of 10 sources checked
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    • cites [51] D. Zhou, W. Dejnirattisai, P. Supasa, C. Liu, A. J. Mentzer, H. M. Ginn, Y. Zhao, H. M. E. Duyvesteyn, A. Tuekprakhon, R. Nutalai, B. Wang, G. C. Paesen, C. Lopez-Camacho, J. Slon-Campos, B. Hallis, N. Coombes, K. Bewley, S. Charlton, T. S. Walter, D. Skelly, S. F. Lumley, C. Dold, R. Levin, T. Dong, A. J. Pollard, J. C. Knight, D. Crook, T. Lambe, E. Clutterbuck, S. Bibi, A. Flaxman, M. Bittaye, S. Belij-Rammerstorfer, S. Gilbert, W. James, M. W. Carroll, P. Klenerman, E. Barnes, S. J. Dunachie, E. E. Fry, J. Mongkolsapaya, J. Ren, D. I. Stuart, G. R. Screaton, Evidence of escape of SARS-CoV- source

      Not checked in the free run.

    • cites [52] R. E. Chen, X. Zhang, J. B. Case, E. S. Winkler, Y. Liu, L. A. VanBlargan, J. Liu, J. M. Errico, X. Xie, N. Suryadevara, P. Gilchuk, S. J. Zost, S. Tahan, L. Droit, J. S. Turner, W. Kim, A. J. Schmitz, M. Thapa, D. Wang, A. C. M. Boon, R. M. Presti, J. A. O’Halloran, A. H. J. Kim, P. Deepak, D. Pinto, D. H. Fremont, J. E. Crowe Jr., D. Corti, H. W. Virgin, A. H. Ellebedy, P.-Y. Shi, M. S. Diamond, Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies. Nat. Med. 27, 717– 726 (2021). 33664494 PMC8058618 source

      Not checked in the free run.

    • cites [53] S. Jangra, C. Ye, R. Rathnasinghe, D. Stadlbauer, F. Krammer, V. Simon, L. Martinez-Sobrido, A. Garcia-Sastre, M. Schotsaert, The E484K mutation in the SARS-CoV-2 spike protein reduces but does not abolish neutralizing activity of human convalescent and post-vaccination sera. medRxiv 10.1101/2021.01.26.21250543 (2021).

      Not checked in the free run.

    • cites [54] K. Wu, A. P. Werner, J. I. Moliva, M. Koch, A. Choi, G. B. E. Stewart-Jones, H. Bennett, S. Boyoglu-Barnum, W. Shi, B. S. Graham, A. Carfi, K. S. Corbett, R. A. Seder, D. K. Edwards, mRNA-1273 vaccine induces neutralizing antibodies against spike mutants from global SARS-CoV-2 variants. bioRxiv 10.1101/2021.01.25.427948 (2021).

      Not checked in the free run.

    • cites [55] X. Xie, J. Zou, C. R. Fontes-Garfias, H. Xia, K. A. Swanson, M. Cutler, D. Cooper, V. D. Menachery, S. Weaver, P. R. Dormitzer, P. Y. Shi, Neutralization of N501Y mutant SARS-CoV-2 by BNT162b2 vaccine-elicited sera. bioRxiv 10.1101/2021.01.07.425740 (2021). 33558724

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    The study population was a selected group of health care workers working with COVID-19 patients, relatively young, predominantly female, with a history of mild COVID-19 disease if previously infected.

    “The study was performed in a selected population of HCWs working with COVID-19 patients who were eligible for rapid vaccination in the Netherlands. The participants were relatively young, predominantly female, with a history of mild COVID-19 disease if previously infected.”
    Quote in the paperNot a substantial claim

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

    Interpretationcitation

    The neutralization data reported here are in line with previous reports.

    “The neutralization data reported here are in line with previous reports (42, 47–49).”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [42] R. R. Goel, S. A. Apostolidis, M. M. Painter, D. Mathew, A. Pattekar, O. Kuthuru, S. Gouma, P. Hicks, W. Meng, A. M. Rosenfeld, S. Dysinger, K. A. Lundgreen, L. Kuri-Cervantes, S. Adamski, A. Hicks, S. Korte, D. A. Oldridge, A. E. Baxter, J. R. Giles, M. E. Weirick, C. M. McAllister, J. Dougherty, S. Long, K. D’Andrea, J. T. Hamilton, M. R. Betts, E. T. Luning Prak, P. Bates, S. E. Hensley, A. R. Greenplate, E. J. Wherry, Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination. Sci. Immunol. 6, eabi6950 (2021). 33858945 PMC8158969 source

      Not checked in the free run.

    • cites [47] Y. Liu, J. Liu, H. Xia, X. Zhang, C. R. Fontes-Garfias, K. A. Swanson, H. Cai, R. Sarkar, W. Chen, M. Cutler, D. Cooper, S. C. Weaver, A. Muik, U. Sahin, K. U. Jansen, X. Xie, P. R. Dormitzer, P. Y. Shi, Neutralizing activity of BNT162b2-elicited serum. N. Engl. J. Med. 384, 1466– 1468 (2021). 33684280 PMC7944950 source

      Not checked in the free run.

    • cites [48] D. Planas, T. Bruel, L. Grzelak, F. Guivel-Benhassine, I. Staropoli, F. Porrot, C. Planchais, J. Buchrieser, M. M. Rajah, E. Bishop, M. Albert, F. Donati, M. Prot, S. Behillil, V. Enouf, M. Maquart, M. Smati-Lafarge, E. Varon, F. Schortgen, L. Yahyaoui, M. Gonzalez, J. De Seze, H. Pere, D. Veyer, A. Seve, E. Simon-Loriere, S. Fafi-Kremer, K. Stefic, H. Mouquet, L. Hocqueloux, S. van der Werf, T. Prazuck, O. Schwartz, Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing antibodies. Nat. Med. 27, 917– 924 (2021). 33772244 source

      Not checked in the free run.

    • cites [49] T. Tada, B. M. Dcosta, M. Samanovic-Golden, R. S. Herati, A. Cornelius, M. J. Mulligan, N. R. Landau, Neutralization of viruses with European, South African, and United States SARS-CoV-2 variant spike proteins by convalescent sera and BNT162b2 mRNA vaccine-elicited antibodies. bioRxiv 10.1101/2021.02.05.430003 (2021).

      Not checked in the free run.

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

    Premisecitation

    Antibodies can have multiple other modes of action that are primarily mediated by IgG1 and IgG3 subclass antibodies.

    “In addition to direct virus neutralization, antibodies can have multiple other modes of action that are primarily mediated by IgG1 and IgG3 subclass antibodies (60).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [60] P. Bruhns, B. Iannascoli, P. England, D. A. Mancardi, N. Fernandez, S. Jorieux, M. Daeron, Specificity and affinity of human Fcgamma receptors and their polymorphic variants for human IgG subclasses. Blood 113, 3716– 3725 (2009). 19018092 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    A single vaccination led to a rapid and strong recall response in COVID-19-recovered participants, without detectable boosting after the second dose.

    “In line with previous studies (42), a single vaccination led to a rapid and strong recall response in COVID-19–recovered participants, without detectable boosting after the second dose.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [42] R. R. Goel, S. A. Apostolidis, M. M. Painter, D. Mathew, A. Pattekar, O. Kuthuru, S. Gouma, P. Hicks, W. Meng, A. M. Rosenfeld, S. Dysinger, K. A. Lundgreen, L. Kuri-Cervantes, S. Adamski, A. Hicks, S. Korte, D. A. Oldridge, A. E. Baxter, J. R. Giles, M. E. Weirick, C. M. McAllister, J. Dougherty, S. Long, K. D’Andrea, J. T. Hamilton, M. R. Betts, E. T. Luning Prak, P. Bates, S. E. Hensley, A. R. Greenplate, E. J. Wherry, Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination. Sci. Immunol. 6, eabi6950 (2021). 33858945 PMC8158969 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    BNT162b2 mRNA vaccination induces robust SARS-CoV-2-specific neutralizing antibodies, ADCC-mediating antibodies, and CD4+ and CD8+ T cells in both COVID-19-recovered and -naive individuals.

    “Here, we show that in both COVID-19–recovered and –naive individuals, BNT162b2 mRNA vaccination induces robust SARS-CoV-2–specific neutralizing antibodies, ADCC-mediating antibodies, and CD4+ and CD8+ T cells.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    ADCC is mainly mediated by the interaction between virus-specific antibodies and Fcγ receptor IIIα (FcγRIIIα, CD16), which is present on NK cells.

    “ADCC is mainly mediated by the interaction between virus-specific antibodies and Fcγ receptor IIIα (FcγRIIIα, CD16), which is, for example, present on NK cells (61–63).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [61] R. D. de Vries, N. J. Nieuwkoop, M. Pronk, E. de Bruin, G. Leroux-Roels, E. G. W. Huijskens, R. S. van Binnendijk, F. Krammer, M. P. G. Koopmans, G. F. Rimmelzwaan, Influenza virus-specific antibody dependent cellular cytoxicity induced by vaccination or natural infection. Vaccine 35, 238– 247 (2017). 27914742 source

      Not checked in the free run.

    • cites [62] R. D. de Vries, N. J. Nieuwkoop, F. R. M. van der Klis, M. P. G. Koopmans, F. Krammer, G. F. Rimmelzwaan, Primary human influenza B virus infection induces cross-lineage hemagglutinin stalk–specific antibodies mediating antibody-dependent cellular cytoxicity. J. Infect. Dis. 217, 3– 11 (2017). 29294018 PMC5853962 source

      Not checked in the free run.

    • cites [63] S. Jegaskanda, K. L. Laurie, T. H. Amarasena, W. R. Winnall, M. Kramski, R. De Rose, I. G. Barr, A. G. Brooks, P. C. Reading, S. J. Kent, Age-associated cross-reactive antibody-dependent cellular cytotoxicity toward 2009 pandemic influenza A virus subtype H1N1. J Infect Dis 208, 1051– 1061 (2013). 23812238 source

      Not checked in the free run.

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

    Interpretationreasoning

    Our study differs from most previously conducted studies because infectious viruses were used to determine neutralizing antibody titers (in contrast to pseudotyped viruses), potentially explaining the increased B.1.1.7 neutralization observation.

    “Our study differs from most previously conducted studies because infectious viruses were used to determine neutralizing antibody titers (in contrast to pseudotyped viruses), potentially explaining this observation.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    NK cells were shown to be decreased in patients with COVID-19 in association with disease severity.

    “NK cells were shown to be decreased in patients with COVID-19 in association with disease severity (64).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [64] M. Zheng, Y. Gao, G. Wang, G. Song, S. Liu, D. Sun, Y. Xu, Z. Tian, Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cell. Mol. Immunol. 17, 533– 535 (2020). 32203188 PMC7091858 source

      Not checked in the free run.

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

    Premisecitation

    A study that followed a sequencing-based approach identified mutations in CD8+ T cell epitopes after sequencing 747 SARS-CoV-2 isolates and showed that tetramer-sorted CD8+ T cell clones responded to mutant peptides in a transcriptionally different manner.

    “A study that followed a sequencing-based approach identified mutations in CD8+ T cell epitopes after sequencing 747 SARS-CoV-2 isolates and showed that tetramer-sorted CD8+ T cell clones responded to mutant peptides in a transcriptionally different manner (70).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [70] B. Agerer, M. Koblischke, V. Gudipati, L. F. Montano-Gutierrez, M. Smyth, A. Popa, J. W. Genger, L. Endler, D. M. Florian, V. Muhlgrabner, M. Graninger, S. W. Aberle, A. M. Husa, L. E. Shaw, A. Lercher, P. Gattinger, R. Torralba-Gombau, D. Trapin, T. Penz, D. Barreca, I. Fae, S. Wenda, M. Traugott, G. Walder, W. F. Pickl, V. Thiel, F. Allerberger, H. Stockinger, E. Puchhammer-Stockl, W. Weninger, G. Fischer, W. Hoepler, E. Pawelka, A. Zoufaly, R. Valenta, C. Bock, W. Paster, R. Geyeregger, M. Farlik, F. Halbritter, J. B. Huppa, J. H. Aberle, A. Bergthaler, SARS-CoV-2 mutations in MHC-I-restric source

      Not checked in the free run.

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

    Premisecitation

    A small study assessed 45 mutations in the B.1.351 S protein and found that only 1 mutation overlapped with a low-prevalent CD8+ T cell epitope.

    “A small study assessed 45 mutations in the B.1.351 S protein, and found that only 1 mutation overlapped with a low-prevalent CD8+ T cell epitope (69).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [69] A. D. Redd, A. Nardin, H. Kared, E. M. Bloch, A. Pekosz, O. Laeyendecker, B. Abel, M. Fehlings, T. C. Quinn, A. A. Tobian, CD8+ T cell responses in COVID-19 convalescent individuals target conserved epitopes from multiple prominent SARS-CoV-2 circulating variants. medRxiv 10.1101/2021.02.11.21251585 (2021). PMC8083629 34322559

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Vaccination-induced antibodies cross-neutralized the variants B.1.1.7 and B.1.351, but the neutralizing capacity and Fc-mediated functionality against B.1.351 were consistently two- to fourfold lower than those against the homologous virus.

    “Vaccination-induced antibodies did cross-neutralize the variants B.1.1.7 and B.1.351, but the neutralizing capacity and Fc-mediated functionality against B.1.351 were consistently two- to fourfold lower than those against the homologous virus.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    In hospitalized patients, a serum neutralizing antibody titer of at least 1:20 was independently associated with the absence of shedding of infectious SARS-CoV-2.

    “In hospitalized patients, we have previously shown that a serum neutralizing antibody titer of at least 1:20 was independently associated with the absence of shedding of infectious SARS-CoV-2 (46).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [46] J. J. A. van Kampen, D. van de Vijver, P. L. A. Fraaij, B. L. Haagmans, M. M. Lamers, N. Okba, J. P. C. van den Akker, H. Endeman, D. Gommers, J. J. Cornelissen, R. A. S. Hoek, M. M. van der Eerden, D. A. Hesselink, H. J. Metselaar, A. Verbon, J. E. M. de Steenwinkel, G. I. Aron, E. C. M. van Gorp, S. van Boheemen, J. C. Voermans, C. A. B. Boucher, R. Molenkamp, M. P. G. Koopmans, C. Geurtsvankessel, A. A. van der Eijk, Duration and key determinants of infectious virus shedding in hospitalized patients with coronavirus disease-2019 (COVID-19). Nat. Commun. 12, 267 (2021). 33431879 PMC7801729 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Viruses used in the PRNT assay were sequenced to rule out additional mutations in the S protein.

    “Viruses used in the assay were isolated from diagnostic specimen at the Department of Viroscience, Erasmus MC, cultured, and subsequently sequenced to rule out additional mutations in the S protein”
    Quote in the paperSubstantial claim

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

    Study design and conductown data

    All S constructs were verified by Sanger sequencing.

    “All S constructs were cloned into a pPPI4 expression vector containing a His tag, verified by Sanger sequencing and subsequently produced in human embryonic kidney–293F cells, and purified as previously described (6, 80).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [6] P. J. M. Brouwer, T. G. Caniels, K. van der Straten, J. L. Snitselaar, Y. Aldon, S. Bangaru, J. L. Torres, N. M. A. Okba, M. Claireaux, G. Kerster, A. E. H. Bentlage, M. M. van Haaren, D. Guerra, J. A. Burger, E. E. Schermer, K. D. Verheul, N. van der Velde, A. van der Kooi, J. van Schooten, M. J. van Breemen, T. P. L. Bijl, K. Sliepen, A. Aartse, R. Derking, I. Bontjer, N. A. Kootstra, W. J. Wiersinga, G. Vidarsson, B. L. Haagmans, A. B. Ward, G. J. de Bree, R. W. Sanders, M. J. van Gils, Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability. Science 3 source

      Not checked in the free run.

    • cites [80] R. N. Kirchdoerfer, C. A. Cottrell, N. Wang, J. Pallesen, H. M. Yassine, H. L. Turner, K. S. Corbett, B. S. Graham, J. S. McLellan, A. B. Ward, Pre-fusion structure of a human coronavirus spike protein. Nature 531, 118– 121 (2016). 26935699 PMC4860016 source

      Not checked in the free run.

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

    Study design and conductnone given

    The sample size for in-depth T cell profiling was limited to 20 donors.

    “The sample size for which in-depth T cell profiling was performed was limited to 20 donors”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Detection of cross-reactive T cells via the AIM assay was previously described.

    “Detection of cross-reactive T cells via the AIM assay was previously described (7, 11, 72).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [7] A. Grifoni, D. Weiskopf, S. I. Ramirez, J. Mateus, J. M. Dan, C. R. Moderbacher, S. A. Rawlings, A. Sutherland, L. Premkumar, R. S. Jadi, D. Marrama, A. M. de Silva, A. Frazier, A. F. Carlin, J. A. Greenbaum, B. Peters, F. Krammer, D. M. Smith, S. Crotty, A. Sette, Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals. Cell 181, 1489– 1501.e15 (2020). 32473127 PMC7237901 source

      Not checked in the free run.

    • cites [11] D. Weiskopf, K. S. Schmitz, M. P. Raadsen, A. Grifoni, N. M. A. Okba, H. Endeman, J. P. C. van den Akker, R. Molenkamp, M. P. G. Koopmans, E. C. M. van Gorp, B. L. Haagmans, R. L. de Swart, A. Sette, R. D. de Vries, Phenotype and kinetics of SARS-CoV-2–specific T cells in COVID-19 patients with acute respiratory distress syndrome. Sci. Immunol. 5, eabd2071 (2020). 32591408 PMC7319493 source

      Not checked in the free run.

    • cites [72] J. Mateus, A. Grifoni, A. Tarke, J. Sidney, S. I. Ramirez, J. M. Dan, Z. C. Burger, S. A. Rawlings, D. M. Smith, E. Phillips, S. Mallal, M. Lammers, P. Rubiro, L. Quiambao, A. Sutherland, E. D. Yu, R. da Silva Antunes, J. Greenbaum, A. Frazier, A. J. Markmann, L. Premkumar, A. de Silva, B. Peters, S. Crotty, A. Sette, D. Weiskopf, Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans. Science 370, 89– 94 (2020). 32753554 PMC7574914 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductown data

    A PRNT50 titer >20 was considered positive based on assay validation.

    “We considered a titer >20 to be positive based on assay validation.”
    Quote in the paperSubstantial claim

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

    Study design and conductown data

    The study did not analyze immune responses to the P.1 VOC.

    “We did not analyze immune responses to the P.1 VOC, originating from Brazil, which also contains mutations in the RBD at positions 417 and 484 (in combination with unique mutations throughout the S protein).”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Previous studies have demonstrated a similar, less pronounced, decrease in neutralization by polyclonal sera after BNT162b2 vaccination against P.1.

    “Although this variant was not investigated in the current study, previous studies have demonstrated a similar, less pronounced, decrease in neutralization by polyclonal sera after BNT162b2 vaccination (47, 77).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [47] Y. Liu, J. Liu, H. Xia, X. Zhang, C. R. Fontes-Garfias, K. A. Swanson, H. Cai, R. Sarkar, W. Chen, M. Cutler, D. Cooper, S. C. Weaver, A. Muik, U. Sahin, K. U. Jansen, X. Xie, P. R. Dormitzer, P. Y. Shi, Neutralizing activity of BNT162b2-elicited serum. N. Engl. J. Med. 384, 1466– 1468 (2021). 33684280 PMC7944950 source

      Not checked in the free run.

    • cites [77] M. Hoffmann, P. Arora, R. Gross, A. Seidel, B. F. Hornich, A. S. Hahn, N. Kruger, L. Graichen, H. Hofmann-Winkler, A. Kempf, M. S. Winkler, S. Schulz, H. M. Jack, B. Jahrsdorfer, H. Schrezenmeier, M. Muller, A. Kleger, J. Munch, S. Pöhlmann, SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies. Cell 184, 2384– 2393.e12 (2021). 33794143 PMC7980144 source

      Not checked in the free run.

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

    Study design and conductown data

    The study only focused on S-specific T cells.

    “we only focused on S-specific T cells”
    Quote in the paperNot a substantial claim

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

    Interpretationcitation

    This T cell cross-reactivity finding is in line with one other recently performed study that additionally showed cross-reactivity to the P.1 and CAL.20C (B.1.429) variants.

    “This is in line with one other recently performed study that additionally showed cross-reactivity to the P.1 and CAL.20C (B.1.429) variants (71).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [71] A. Tarke, J. Sidney, N. Methot, Y. Zhang, J. M. Dan, B. Goodwin, P. Rubiro, A. Sutherland, R. da Silva Antunes, A. Frazier, S. A. Rawlings, D. M. Smith, B. Peters, R. H. Scheuermann, D. Weiskopf, S. Crotty, A. Grifoni, A. Sette, Negligible impact of SARS-CoV-2 variants on CD4+ and CD8+ T cell reactivity in COVID-19 exposed donors and vaccinees. bioRxiv 10.1101/2021.02.27.433180 (2021). PMC8249675 34230917

      Not checked in the free run.

  • May combine two claims.

    Study design and conductcitation

    The Luminex bead assay had specificity 99.7% and sensitivity 91.6%, determined using a heterogeneous sample set including asymptomatic and mild to severe COVID-19 cases, prepandemic population samples, and samples of persons infected with various viruses including endemic coronaviruses as negative controls.

    “The specificity (99.7%) and sensitivity (91.6%) of the assay were determined using a heterogeneous sample set including asymptomatic and mild to severe COVID-19 cases as representative of COVID-19 cases in the general population, as well prepandemic population samples and samples of persons infected with various viruses, including endemic coronaviruses, as negative controls (23).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [23] G. den Hartog, E. R. A. Vos, L. L. van den Hoogen, M. van Boven, R. M. Schepp, G. Smits, J. van Vliet, L. Woudstra, A. J. Wijmenga-Monsuur, C. C. E. van Hagen, E. A. M. Sanders, H. E. de Melker, F. R. M. van der Klis, R. S. van Binnendijk, Persistence of antibodies to SARS-CoV-2 in relation to symptoms in a nationwide prospective study. Clin. Infect. Dis. 2021, ciab172 (2021). PMC7929058 33624751 source

      Not checked in the free run.

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

    Study design and conductown data

    CD16 expression in the NK92.05-CD16 cell line was monitored by flow cytometry.

    “CD16 expression in this cell line was monitored by flow cytometry by staining with anti–CD16-AF647”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    Low-frequency samples (<10,000 cells in CD4 gate and <5000 cells in CD8 gate) were excluded from analysis.

    “Low-frequency samples (<10,000 cells in CD4 gate and <5000 cells in CD8 gate) were excluded from analysis.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    Appropriate statistical tests were selected to compare normal or nonnormal distributed values, paired or unpaired samples, and taking into account missing values.

    “Appropriate tests were selected to compare normal or nonnormal distributed values, paired or unpaired samples, and taking into account missing values.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    For N=11 of 20 donors assessed, SARS-CoV-2 specificity in the CD4+ subset was confirmed by gating CD137+OX40+ cells.

    “For N = 11 of 20 donors assessed, SARS-CoV-2 specificity in the CD4+ subset was confirmed by gating CD137+OX40+ cells.”
    Quote in the paperNot a substantial claim

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

    Study design and conductcitation

    The ADCC assay was performed as previously described.

    “ADCC assay was performed as previously described (61).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [61] R. D. de Vries, N. J. Nieuwkoop, M. Pronk, E. de Bruin, G. Leroux-Roels, E. G. W. Huijskens, R. S. van Binnendijk, F. Krammer, M. P. G. Koopmans, G. F. Rimmelzwaan, Influenza virus-specific antibody dependent cellular cytoxicity induced by vaccination or natural infection. Vaccine 35, 238– 247 (2017). 27914742 source

      Not checked in the free run.

56 of 56

  • The paper relies on this without support.

    Little is known about T cell cross-reactivity with SARS-CoV-2 variants of concern.

    “Although several studies have demonstrated that some VOCs may be capable of evading infection or vaccination-induced neutralizing antibodies, little is known about T cell cross-reactivity with VOCs.”

  • The paper relies on this without support.

    The B.1.1.7 and B.1.351 variants both contain the N501Y mutation.

    “The B.1.1.7 and B.1.351 variants both contain the signature mutation N501Y”

  • The paper relies on this without support.

    The N501Y mutation is associated with increased affinity for the ACE2 receptor.

    “associated with increased affinity for the ACE2 (angiotensin converting enzyme 2) receptor.”
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?

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.

  • Incorrect percentage in the in-depth vaccination-interval subgroup

    Minor

    Ten of the 13 COVID-19-recovered participants selected for in-depth analysis is 76.9%, not 85.6%.

    Reported 85.6 · recomputed 76.923077

  • Incorrect percentage for naive male participants

    Minor

    Table 1 lists 33 males among 98 COVID-19-naive participants. That is 33.7%, not 35.6%.

    Reported 35.6 · recomputed 33.673469

  • Cohort median age differs between Results and Table 1

    Minor

    The Results state a median age of 41 years, while the "All" column of Table 1 gives 40.

  • Post-vaccination timing variability conflicts with stated collection windows

    Minor

    The stated collection windows are 14-21 and 21-28 days after the first and second doses. Given the reported means, observations confined to those windows cannot have SDs as large as 3.2 and 5.9 days, respectively.

4 of 4

Cites

Flagged first, then by citations

Research works printed but not linked: 3

  1. N. Zucman, F. Uhel, D. Descamps, D. Roux, J. D. Ricard, Severe reinfection with South African SARS-CoV-2 variant 501Y.V2: A case report. Clin. Infect. Dis. 2021, ciab014 (2021).
  2. X. Xie, J. Zou, C. R. Fontes-Garfias, H. Xia, K. A. Swanson, M. Cutler, D. Cooper, V. D. Menachery, S. Weaver, P. R. Dormitzer, P. Y. Shi, Neutralization of N501Y mutant SARS-CoV-2 by BNT162b2 vaccine-elicited sera. bioRxiv 10.1101/2021.01.07.425740 (2021). · DOI · Paper page
  3. M. McCallum, J. Bassi, A. Marco, A. Chen, A. C. Walls, J. D. Iulio, M. A. Tortorici, M. J. Navarro, C. Silacci-Fregni, C. Saliba, M. Agostini, D. Pinto, K. Culap, S. Bianchi, S. Jaconi, E. Cameroni, J. E. Bowen, S. W. Tilles, M. S. Pizzuto, S. B. Guastalla, G. Bona, A. F. Pellanda, C. Garzoni, W. C. Van Voorhis, L. E. Rosen, G. Snell, A. Telenti, H. W. Virgin, L. Piccoli, D. Corti, D. Veesler, SARS-CoV-2 immune evasion by variant B.1.427/B.1.429. bioRxiv 10.1101/2021.03.31.437925 (2021). · DOI

Cited by

Sorted by citations

Authors
Geers, D., Shamier, M. C., Bogers, S., den Hartog, G., Gommers, L., Nieuwkoop, N. N., Schmitz, K. S., Rijsbergen, L. C., van Osch, J. A. T., Dijkhuizen, E., Smits, G., Comvalius, A., van Mourik, D., Caniels, T. G., van Gils, M. J., Sanders, R. W., Oude Munnink, B. B., Molenkamp, R., de Jager, H. J., Haagmans, B. L., de Swart, R. L., Koopmans, M. P. G., van Binnendijk, R. S., de Vries, R. D., & GeurtsvanKessel, C. H.
Affiliations
  • Erasmus MC (NL)
  • Centre for Immunology of Infectious Diseases and Vaccines, National Institute for Public Health and the Environment, Bilthoven, Netherlands.
  • Department of Viroscience, Erasmus MC, Rotterdam, Netherlands.
  • National Institute for Public Health and the Environment (NL)
  • Amsterdam University Medical Centers (NL)
  • Department of Medical Microbiology, Amsterdam UMC, Amsterdam, Netherlands.
  • Cornell University (US)
  • Department of Occupational Health Services, Erasmus MC, Rotterdam, Netherlands.
Corresponding author
  • Geers, Daryl
  • Shamier, Marc C.
  • GeurtsvanKessel, Corine H.
ORCID
Venue
Science Immunology
Publisher
American Association for the Advancement of Science (AAAS)
Published
2021-05-28
Volume
6
Issue
59
ISSN
2470-9468 (ISSN-L)
DOI
10.1126/sciimmunol.abj1750
PMC
PMC9268159
OpenAlex
W3165367963
Cited by
529
References
83
Citations by year
2026: 15 · 2025: 40 · 2024: 75 · 2023: 94 · 2022: 204 · 2021: 101
FWCI
37.69
Type
journal article
Language
en
Open access
Licence
Locations
  • Science Immunology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, cc-by)
  • Pure Amsterdam UMC (submittedVersion, cc-by)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
  • EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, cc-by)
  • Rivm Repository (Netherlands National Institute for Public Health and the Environment) (submittedVersion)
  • Rivm (National Institute for Public Health and the Environment) (submittedVersion)
Funders
  • Bill and Melinda Gates Foundation (INV-002022)
  • Netherlands Organization for Scientific Research (VICI)
  • ZonMW (10150062010005)
  • Amsterdam UMC (AMC Fellowship)
  • Top Sector Life Sciences Health; Health~Holland (EMCLHS20017)
  • European Union’s Horizon 2020 RECoVER (101003589)
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
  • Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
Keywords
SARS-CoV-2, variants of concern, spike protein mutations, CD4+ T cells, humoral immunity, T cell response, vaccine recipients, immune evasion, SARS-CoV-2 spike protein
MeSH terms
COVID-19, SARS-CoV-2, COVID-19 Vaccines, Antibodies, Viral, Cell Line, Cross Reactions, Humans, Immunologic Memory, Vaccination, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Spike Glycoprotein, Coronavirus

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 ›

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