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Cited by 276SARS-CoV-2 and COVID-19 Researchvaccines and immunoinformatics approachesAnimal Virus Infections Studies

SARS-CoV-2 mRNA vaccination induces functionally diverse antibodies to NTD, RBD, and S2

Open access
Amanat, Fatima, Thapa, Mahima, Lei, Tinting, Ahmed, Shaza M. Sayed, Adelsberg, Daniel C., Carreño, Juan Manuel, Strohmeier, Shirin, Schmitz, Aaron J. +39 more·2021·Cell
DOI 10.1016/j.cell.2021.06.005PMC PMC8185186
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Abstract

In this study we profiled vaccine-induced polyclonal antibodies as well as plasmablast-derived mAbs from individuals who received SARS-CoV-2 spike mRNA vaccine. Polyclonal antibody responses in vaccinees were robust and comparable to or exceeded those seen after natural infection. However, the ratio of binding to neutralizing antibodies after vaccination was greater than that after natural infection and, at the monoclonal level, we found that the majority of vaccine-induced antibodies did not have neutralizing activity. We also found a co-dominance of mAbs targeting the NTD and RBD of SARS-CoV-2 spike and an original antigenic-sin like backboost to spikes of seasonal human coronaviruses OC43 and HKU1. Neutralizing activity of NTD mAbs but not RBD mAbs against a clinical viral isolate carrying E484K as well as extensive changes in the NTD was abolished, suggesting that a proportion of vaccine-induced RBD binding antibodies may provide substantial protection against viral variants carrying single E484K RBD mutations.

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Crossref · 10.1016/j.cell.2021.06.005

Cites

92 of 92 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 47 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    At peak response, vaccinees had the highest proportion of binding to neutralizing antibody titers.

    “When determined at the time of peak response, the vaccinees had the highest proportion of binding to neutralizing antibody titers”
    Quote in the paperSubstantial claim
  • Findingown data

    For V3, only one RBD-binding monoclonal antibody out of 21, 5%, displayed neutralizing activity.

    “For V3, only one (an RBD binder) out of 21 mAbs (5%) displayed neutralizing activity”
    Quote in the paperSubstantial claim
  • Findingown data

    For V5, a single NTD antibody neutralized authentic SARS-CoV-2, 17%.

    “For V5, a single NTD antibody neutralized authentic SARS-CoV-2 (17%)”
    Quote in the paperNot a substantial claim
  • Findingown data

    One vaccinee, V4, produced anti-spike and anti-RBD titers comparable to the high-titer convalescent group.

    “while one vaccinee (V4) produced titers comparable to the high titer group.”
    Quote in the paperNot a substantial claim
  • Findingown data

    A substantial number of isolated monoclonal antibodies bound NTD: 14% for V3, 33% for V5, and 33% for V6.

    “A substantial number of the isolated mAbs bound to NTD including 14% for V3, 33% for V5, and 33% for V6”
    Quote in the paperSubstantial claim
  • May combine two claims. 37
  • Classified as probably not a substantial claim. 35

  • May combine two claims.

    Findingown data

    All vaccinees displayed high neutralizing antibody titers against authentic SARS-CoV-2, although V4 responded with delayed kinetics.

    “all vaccinees displaying high titers, even though V4 responded with delayed kinetics”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Anti-RBD antibody titers appeared to decline faster than anti-spike antibody titers, which appeared more stable over time.

    “anti-RBD antibody titers seemed to decline faster than anti-spike antibody titers, which appeared to be more stable over time”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The antibody response peaked one week after the second vaccine dose and then declined over the following weeks.

    “the antibody response peaked 1 week after the second vaccine dose, followed by a decline in titers over the following weeks”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In vaccine recipients, polyclonal antibody responses were strong and were comparable to or higher than those observed after natural infection.

    “Polyclonal antibody responses in vaccinees were robust and comparable to or exceeded those seen after natural infection.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The highest neutralizing potency was found for monoclonal antibody PVI.V5-6, an NTD binder, followed by PVI.V6-4, an RBD binder.

    “Interestingly, the highest neutralizing potency was found for mAb PVI.V5-6, an NTD binder followed by PVI.V6-4, an RBD binder.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    At peak response, the vaccine group's neutralization titers fell in the upper range of the high convalescent group but did not markedly exceed it.

    “although at the peak response, the vaccine group mounted neutralization titers that fell in the upper range for the high convalescent group, they did not exceed that group markedly”
    Quote in the paperSubstantial claim

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

    Findingown data

    Only three monoclonal antibodies were not accounted for in terms of binding target: two for V3 and one for V5.

    “Only three mAbs were not accounted for in terms of binding target (two for V3 and one for V5”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The spike binding to RBD binding ratio did not differ between vaccinees and convalescent individuals, except for a trend toward proportionally less RBD binding over time in vaccinees.

    “We also investigated the spike binding to RBD binding ratio and found no difference to convalescent individuals except a general trend toward proportionally less RBD binding over time in the vaccinees”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In four vaccinees, antibody titers against α-coronavirus 229E and NL63 spike proteins were detectable before vaccination but did not increase substantially after vaccination.

    “Antibody titers in four vaccinees against spike protein from α-coronaviruses 229E and NL63 were detectable at the pre-vaccination time point but did not increase substantially after vaccination”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    For V6, the highest frequency of neutralizing antibodies was 33%, with one RBD neutralizer and four NTD neutralizers.

    “The highest frequency of neutralizing antibodies was found in V6 (33%) with one RBD neutralizer and four NTD neutralizers”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    A total of 21 spike-reactive monoclonal antibodies were isolated from V3, 6 from V5, and 15 from V6.

    “A total of 21 (40 mAbs were screened, with 28 being clonally unique, Table S2) spike-reactive mAbs were isolated from V3, 6 (82 screened, 20 unique) from V5, and 15 (84 screened, 24 unique) from V6”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The two RBD-binding antibodies lost no or little neutralizing activity against B.1.1.7: PVI.V6-4 lost none and PVI.V3-9 lost little.

    “The two RBD binding antibodies lost no (PVI.V6-4) or little (PVI.V3-9) neutralizing activity against B.1.1.7.”
    Quote in the paperSubstantial claim

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

    Findingown data

    The activity of PVI.V3-9 against PV14252 increased slightly.

    “In fact, the activity of PVI.V3-9 increased slightly”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Complete loss of convalescent serum binding was rare, while 2- to 4-fold reduction in binding was more common.

    “However, complete loss of binding was rare and 2- to 4-fold reduction in binding was more common.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    PVI.V3-9 lost all neutralizing activity against B.1.351, and PVI.V6-4 retained low but measurable activity.

    “However, PVI.V3-9 lost all activity against B.1.351 and the remaining neutralizing activity of PVI.V6-4 was low (but measurable).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    One vaccinee yielded no RBD-binding mAbs, though mAb numbers were low and serum recognized RBD.

    “In one vaccinee not a single RBD binding mAbs was isolated with the caveats that the overall number of mAbs derived from that individual were low and their polyclonal serum antibody responses included RBD recognition.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The SARS-CoV-2 isolate PV14252 had two NTD mutations, W64R and L141Y, one NTD deletion, Δ142-145, and the E484K mutation in the RBD.

    “the SARS-CoV-2 isolate PV14252 (Clade 20C, Pango lineage B.1) that featured two mutations (W64R, L141Y) and one deletion (Δ142-145) in the NTD as well as the E484K mutation in the RBD”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Almost all convalescent sera bound better to N501Y RBD than to wild-type RBD, with an average of 129% compared to wild-type.

    “Interestingly, almost all sera bound better to N501Y RBD (B.1.1.7) than to wild-type RBD (average 129% compared to wild-type).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    For E484K, F484A, B.1.351, and P.1, the highest reduction in vaccinated sera was also approximately 2-fold, but this did not apply to all six vaccinees.

    “The highest reduction observed for E484K, F484A, B.1.351, and P.1 were also approximately 2-fold but this did not apply to all six vaccinees.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingreasoning

    Vaccinees responded to OC43 and HKU1 spike proteins but not to 229E and NL63.

    “Vaccinated individuals mounted a response to spike proteins from OC43 and HKU1 but not to α-coronaviruses 229E and NL63.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    All but one NTD monoclonal antibody, PVI.V6-11, lost neutralizing activity against B.1.1.7, and all NTD monoclonal antibodies lost neutralizing activity against B.1.351.

    “All but one (PVI.V6-11) NTD mAbs lost neutralizing activity against B.1.1.7 and all of them lost neutralizing activity against B.1.351”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    mRNA vaccination appears to induce a high antibody response with relatively homogeneous titers.

    “mRNA vaccination appears to induce a high antibody response of relatively homogeneous titers.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Three monoclonal antibodies showed strong OC43 spike binding (PVI.V3-8, PVI.V3-12, and PVI.V6-1), PVI.V3-17 showed intermediate binding, and PVI-V5-1 bound very weakly.

    “Three mAbs showed strong binding (PVI.V3-8, PVI.V3-12, and PVI.V6-1), while PVI.V3-17 showed an intermediate binding phenotype and PVI-V5-1 bound very weakly.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Several monoclonal antibodies had a negative impact on binding to B.1.351, while binding was almost unaffected by mutations in the P.1 variant RBD.

    “Although there was a negative impact on binding of several mAbs to the B.1.351 variant, binding was almost unaffected by the mutations in the P.1 variant RBD.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Five of seven neutralizing mAbs bound NTD, and two bound RBD.

    “five out of seven neutralizing antibodies isolated in this study bound to the NTD and only two targeted the RBD.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Neutralizing activity of sera from V2, V5, and V6 slightly increased against PV14252, while activity for V1, V3, and V4 decreased.

    “The activity of sera from V2, V5, and V6 slightly increased while the activity for V1, V3, and V4 decreased.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Among the HKU1-binding monoclonal antibodies, PVI.V6-1 showed very weak binding, while PVI.3-8 and PVI.3-12 had low minimal binding concentrations indicating higher affinity.

    “Of these, PVI.V6-1 showed only very weak binding while PVI.3-8 and PVI.3-12 had low minimal binding concentrations (MBCs) indicating higher affinity”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    NTD and RBD binders were found at similar levels, and many mAbs bound outside both regions.

    “We found similar levels of NTD and RBD binders with many mAbs binding to epitopes outside the RBD and the NTD.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    All NTD mAbs lost neutralization against B.1.351, and all but one lost it against B.1.1.7.

    “All NTD mAbs also lost neutralizing activity against B.1.351 and all but one lost activity against B.1.1.7.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingreasoning

    Two neutralizing RBD antibodies had reduced binding to E484K mutant RBD but similar or higher potency against virus with only E484K in RBD.

    “the two neutralizing antibodies against the RBD showed some reduced binding to a mutant RBD carrying the E484K mutation while having similar or even increased neutralizing potency against a variant virus carrying the E484K mutation as the only change in its RBD.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    SARS-CoV-2 infection induces an original antigenic sin-type immune response against human coronaviruses to which most people have pre-existing immunity.

    “It has been reported that SARS-CoV-2 infection induces an original antigenic sin-type immune response against human coronaviruses (hCoVs) to which the majority of the human population has pre-existing immunity”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Aydillo et al., 2021 source

      Not checked in the free run.

    • cites Song et al., 2020

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    B cells and monoclonal antibodies isolated from vaccinated individuals have also been studied with RBD-focused sorting.

    “This is also true for B cells and monoclonal antibodies (mAbs) isolated from vaccinated individuals”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Wang et al., 2021 source

      Not checked in the free run.

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

    Premisecitation

    Antibodies that bind the RBD can potently block virus attachment to ACE2 and thereby neutralize the virus.

    “Antibodies binding to the RBD can potently block attachment of the virus to ACE2 and thereby neutralize the virus”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Barnes et al., 2020 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The vaccine response was more focused on non-neutralizing antibodies or induced less potent neutralizing antibodies in general, or both.

    “indicating an immune response more focused on non-neutralizing antibodies or an induction of less potent neutralizing antibodies in general (or both)”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    The SARS-CoV-2 spike RBD directly interacts with ACE2, the cellular receptor that mediates host cell entry.

    “it directly interacts with the cellular receptor angiotensin converting enzyme 2 (ACE2) which mediates host cell entry”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Letko et al., 2020 source

      Not checked in the free run.

    • cites Wrapp et al., 2020 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Data on non-neutralizing antibodies were already apparent in early phase clinical trials but remained unrecognized at the time.

    “These data were already apparent in the early phase clinical trials but remained unrecognized at the time”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Walsh et al., 2020

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    The study sorted and cloned plasmablasts in an antigen-agnostic, unbiased manner.

    “We, in contrast, took an unbiased approach to sort and clone plasmablasts in an antigen-agnostic manner.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Two recent studies performed similarly unbiased plasmablast analyses for individuals naturally infected with SARS-CoV-2.

    “Two recent studies have performed a similarly unbiased plasmablast analysis for individuals naturally infected with SARS-CoV-2”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Cho et al., 2021

      Not checked in the free run.

    • cites Huang et al., 2021

      Not checked in the free run.

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

    Premisecitation

    A backboost to β-coronaviruses has been reported for natural SARS-CoV-2 infection.

    “has already been shown for natural infection with SARS-CoV-2 where a “backboost” to β-coronaviruses was also found (Aydillo et al., 2021; Song et al., 2020).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Aydillo et al., 2021 source

      Not checked in the free run.

    • cites Song et al., 2020

      Not checked in the free run.

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

    Study design and conductnone given

    Wild-type SARS-CoV-2 and PV14252 were tested in parallel to ensure that the assay setup allowed comparison.

    “Wild-type SARS-CoV-2 and PV14252 were tested in parallel to ensure that the assay setup for both viruses allowed comparison.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    A deep mutational scanning study of mRNA-1273 vaccinee sera found a strongly RBD-focused response.

    “a recent deep mutational scanning paper with sera from mRNA-1273 vaccinees found a very strong RBD-focused response (Greaney et al., 2021a).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Greaney et al., 2021a

      Not checked in the free run.

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

    Study design and conductown data

    The current data cannot rule out de novo induction of the cross-reactive mAbs.

    “we cannot exclude this possibility with our current data.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Recent natural-infection plasmablast studies found similar RBD/NTD co-dominance.

    “Recent studies analyzing the plasmablast response after natural infection have found a similar co-dominance of RBD and NTD (Cho et al., 2021; Huang et al., 2021)”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Cho et al., 2021

      Not checked in the free run.

    • cites Huang et al., 2021

      Not checked in the free run.

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

    Interpretationnone given

    Some antibodies may lose neutralization due to reduced affinity but still bind.

    “although some antibodies may lose neutralizing activity due to reduced affinity, they do still bind.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    Viruses were deep sequenced to confirm no culture mutations.

    “The viruses were subjected to deep sequencing to ensure that no mutations had taken place in culture.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    The study did not perform longitudinal analysis of convalescent sera.

    “We have also not included a longitudinal analysis of the convalescent sera in the study”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Non-neutralizing antibody production after the first mRNA dose is substantial and occurs when neutralizing titers are low or absent.

    “it is substantial and occurs during a time when neutralizing antibody titers are either very low or absent (Baden et al., 2020; Dagan et al., 2021; Polack et al., 2020).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Baden et al., 2020 source

      Not checked in the free run.

    • cites Dagan et al., 2021 source

      Not checked in the free run.

    • cites Polack et al., 2020 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    Plasmablast analysis is generally not quantitative.

    “While plasmablast analysis is in general not quantitative (e.g., one clone per clonotype is selected, etc.)”
    Quote in the paperSubstantial claim

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

    Study design and conductown data

    The study protocols were reviewed and approved by the Mount Sinai Hospital IRB.

    “The study protocols for the collection of clinical specimens from individuals with and without SARS-CoV-2 infection by the Personalized Virology Initiative were reviewed and approved by the Mount Sinai Hospital Institutional Review Board (IRB-16-16772; IRB-16-00791; IRB-20-03374).”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    The passage 2 primary isolate sequence matched the clinical specimen sequence.

    “The sequence of the passage 2 viral isolate was identical to the sequence obtained directly from the clinical specimen.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    Specimens were coded before processing and analysis.

    “All specimens were coded prior to processing and analysis.”
    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

    The total number of cells recovered by RNA sequencing was 6,608 for V3, 5,256 for V5, and 6,325 for V6.

    “Total recovered cells by RNA sequencing were V3: 6,608, V5: 5,256, and V6: 6,325”
    Quote in the paperNot a substantial claim

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

    Study design and conductreasoning

    Comparison with published infected-individual data is less accurate than a side-by-side comparison.

    “We have compared our data with published data from plasmablast analysis after SARS-CoV-2 infection but a side-by-side comparison would have been more accurate.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    All participants gave written informed consent before specimen and clinical data collection.

    “All participants provided written informed consent prior to collection of specimen and clinical information.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    Blank wells without primary antibody were used to assess plate background.

    “Eight wells on each plate received no primary antibody (blank wells) and the optical density in those wells was used to assess background.”
    Quote in the paperNot a substantial claim

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

    Interpretationreasoning

    The converse mechanism may operate here.

    “the converse mechanism could be at play here.”
    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

    Authentic SARS-CoV-2 work was performed in a BSL3 laboratory under institutional biosafety guidelines.

    “All work with authentic SARS-CoV-2 (isolate USA-WA1/2020 and PV14252) was done in a biosafety level 3 (BSL3) laboratory following institutional biosafety guidelines”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    The study did not analyze plasmablasts from SARS-CoV-2-infected individuals.

    “Another limitation is the lack of plasmablast analysis of SARS-CoV-2-infected individuals.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Increased affinity as a viral escape mechanism has been described previously.

    “Increased affinity as an escape mechanism for viruses has been described in the past (Hensley et al., 2009; O’Donnell et al., 2012)”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Hensley et al., 2009 source

      Not checked in the free run.

    • cites O’Donnell et al., 2012 source

      Not checked in the free run.

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

    Study design and conductown data

    BLI measurements were repeated in independent experiments.

    “All measurements were repeated in subsequent independent experiments.”
    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

    The B.1.351 virus acquired a WRAR polybasic cleavage site change in culture, with no other unexpected mutations.

    “The polybasic cleavage site changed to WRAR in the B.1.351 variant virus during cultivation in cell culture (as known for this virus at BEI Resources) and no other unexpected mutations occurred.”
    Quote in the paperNot a substantial claim

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

    Study design and conductreasoning

    The small participant number makes the study qualitative rather than quantitative.

    “The first limitation is the small number of study participants, which makes this study a qualitative rather than a quantitative study.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    The study did not analyze pre-vaccination memory B cells or BCR sequences, so recall origin lacks ultimate proof.

    “we lack the ultimate proof for that since we did not analyze pre-vaccination memory B cells and B cell receptor sequences.”
    Quote in the paperSubstantial claim

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

    Study design and conductown data

    The integrated RNA sequencing object contained 12,568 cells, with 4,584 from V3, 3,523 from V5, and 4,461 from V6.

    “The integrated RNA sequencing object included 12,568 cells with V3: 4,584, V5: 3,523, and V6: 4,461 cells.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    Remdesivir served as assay control for wild-type and patient isolate viruses.

    “For assay control, remdesivir was used against both the wild type virus as well as the patient isolate.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    The mean percentage of reads mapped to the genome across the sequencing runs was 90.64%.

    “with a mean of 90.64% read mapped to the genome”
    Quote in the paperNot a substantial claim
66 of 66

  • The paper relies on this without support.

    All viral variants of concern are heavily mutated in the NTD region.

    “Since all viral variants of concern are heavily mutated in this region”
1 of 1

Claims other papers make about this one

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

  • Cross-reactive clones were not identified in all individuals and comprised a small fraction of responding B cells, consistent with a similar analysis of SARS-CoV-2 mRNA vaccine-induced plasmablasts.

    “However, these cross-reactive clones were not identified in all individuals and comprised a small fraction of responding B cells, consistent with a similar analysis of SARS-CoV-2 mRNA vaccine-induced plasmablasts37.”

    From SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses (2021) · cites this paper as [37]

  • Q493R mediates resistance to CB6 (class 1) and to LY-CoV555 and 2-15 (class 2).

    “Q493R, which was previously shown to affect binding of CB6 and LY-CoV555 (ref.28 ) as well as polyclonal sera 29 , mediated resistance to CB6 (class 1) as well as to LY-CoV555 and 2-15 (class 2)”

    From Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2 (2022) · cites this paper as [29]

  • Q493R was previously shown to affect binding of CB6 and LY-CoV555 as well as polyclonal sera.

    “Q493R, which was previously shown to affect binding of CB6 and LY-CoV555 (ref.28 ) as well as polyclonal sera 29”

    From Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2 (2022) · cites this paper as [29]

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.

  • Convalescent antibody ratios are interpreted in opposite directions

    Major

    The results say lower-titer convalescent individuals had more binding relative to neutralizing antibodies. The discussion instead says low-titer serum had the highest relative amount of neutralizing antibodies and higher-titer serum had more binding antibodies.

  • Figure caption names a different variant

    Minor

    The Figure 4 caption lists B.1.315 among the three variants of concern, while the introduction lists B.1.351 in its place.

2 of 2

Cites

Flagged first, then by citations

8 of the 100 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. Annavajhala, 2021, A Novel SARS-CoV-2 Variant of Concern, B.1.526, Identified in New York, medRxiv

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Authors
Amanat, F., Thapa, M., Lei, T., Ahmed, S. M. S., Adelsberg, D. C., Carreño, J. M., Strohmeier, S., Schmitz, A. J., Zafar, S., Zhou, J. Q., Rijnink, W., Alshammary, H., Borcherding, N., Reiche, A. G., Srivastava, K., Sordillo, E. M., van Bakel, H., Ahmed, B., Altman, D., Amoako, A., Awawda, M., Beach, K., Bermúdez-González, C., Chernet, R., Eaker, L., Fabre, S., Ferreri, E. D., Floda, D., Gleason, C., Kleiner, G., Jurczyszak, D., Matthews, J., Mendez, W., Mulder, L. C. F., Polanco, J., Russo, K., Salimbangon, A., Saksena, M., Shin, A. S., Sominsky, L., Suthakaran, S., Wajnberg, A., Turner, J. S., Bajic, G., Simon, V., Ellebedy, A. H., & Krammer, F.
Affiliations
  • Icahn School of Medicine at Mount Sinai (US)
  • Washington University in St. Louis (US)
  • AbCellera (Canada) (CA)
Corresponding author
  • Bajic, Goran
  • Simon, Viviana
  • Ellebedy, Ali H.
  • Krammer, Florian
ORCID
Venue
Cell
Publisher
Elsevier BV
Published
2021-07
Volume
184
Issue
15
Pages
3936-3948.e10
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2021.06.005
PMC
PMC8185186
OpenAlex
W3171375949
Cited by
273
References
100
Citations by year
2026: 15 · 2025: 25 · 2024: 36 · 2023: 52 · 2022: 94 · 2021: 51
FWCI
18.53
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Open Philanthropy Project (2020-215611)
  • JPB Foundation (5384, 5T32CA009547)
  • NIAID (5T32CA009547, 75N93019C00051, U01AI141990, U01AI150747, HHSN272201400006C)
  • AbbVie
  • Icahn School of Medicine at Mount Sinai
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, mRNA vaccines, spike protein, N-terminal domain, receptor binding domain, S2 subunit, polyclonal antibodies, monoclonal antibodies, neutralizing antibodies, original antigenic sin, seasonal human coronaviruses, antibody response
MeSH terms
Protein Domains, Angiotensin-Converting Enzyme 2, SARS-CoV-2, COVID-19 Vaccines, Antibodies, Monoclonal, Antibodies, Viral, Antibody Formation, Binding, Competitive, Humans, Immunoglobulin G, Mutation, RNA, Messenger, Vaccination, Amino Acid Substitution, Somatic Hypermutation, Immunoglobulin, Antibodies, Neutralizing, 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.

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