The DOI matches its Crossref record; 62 of the 62 references it cites were found in a registry or an index; none of the 19 sources its claims cite is checked for support yet.
Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7
Open accessPublished version of a preprint
Abstract
The COVID-19 pandemic has had widespread effects across the globe, and its causative agent, SARS-CoV-2, continues to spread. Effective interventions need to be developed to end this pandemic. Single and combination therapies with monoclonal antibodies have received emergency use authorization 1-3, and more treatments are under development 4-7. Furthermore, multiple vaccine constructs have shown promise 8, including two that have an approximately 95% protective efficacy against COVID-19 9,10. However, these interventions were directed against the initial SARS-CoV-2 virus that emerged in 2019. The recent detection of SARS-CoV-2 variants B.1.1.7 in the UK 11 and B.1.351 in South Africa 12 is of concern because of their purported ease of transmission and extensive mutations in the spike protein. Here we show that B.1.1.7 is refractory to neutralization by most monoclonal antibodies against the N-terminal domain of the spike protein and is relatively resistant to a few monoclonal antibodies against the receptor-binding domain. It is not more resistant to plasma from individuals who have recovered from COVID-19 or sera from individuals who have been vaccinated against SARS-CoV-2. The B.1.351 variant is not only refractory to neutralization by most monoclonal antibodies against the N-terminal domain but also by multiple individual monoclonal antibodies against the receptor-binding motif of the receptor-binding domain, which is mostly due to a mutation causing an E484K substitution. Moreover, compared to wild-type SARS-CoV-2, B.1.351 is markedly more resistant to neutralization by convalescent plasma (9.4-fold) and sera from individuals who have been vaccinated (10.3-12.4-fold). B.1.351 and emergent variants 13,14 with similar mutations in the spike protein present new challenges for monoclonal antibody therapies and threaten the protective efficacy of current vaccines.
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38 Own result · 11 Not checked yet · 11 Own method · 9 Own interpretation
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“Here we show that B.1.1.7 is refractory to neutralization by most monoclonal antibodies against the N-terminal domain of the spike protein and is relatively resistant to a few monoclonal antibodies against the receptor-binding domain.”
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In the paper
“351 is mediated by the E484K substitution; the complete loss of activity of 910-30 is mediated by the K417N substitution; and the marked reduction in activity of REGN10933 is mediated by K417N and E484K, as has previously been reported 28 .”
§ Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7 > Monoclonal antibodies
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In the paper
“Here we show that B.1.1.7 is refractory to neutralization by most monoclonal antibodies against the N-terminal domain of the spike protein and is relatively resistant to a few monoclonal antibodies against the receptor-binding domain.”
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In the paper
“Both B.1.1.7 and B.1.351are markedly resistant to neutralization by antibodies 5-24 and 4-8 20 , as well as by 4A8 29 , all of which target the antigenic supersite in the NTD 18 (Fig. 2b).”
§ Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7 > Monoclonal antibodies
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In the paper
“For neutralization of B.1.351,however, the activities of 910-30, 2-15 20 , LY-CoV555 (bamlanivimab) 1,23 , C121 24 and REGN10933 (casirivimab) 2 are completely or markedly abolished.”
§ Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7 > Monoclonal antibodies
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In the paper
“The B.1.351variant is not only refractory to neutralization by most monoclonal antibodies against the N-terminal domain but also by multiple individual monoclonal antibodies against the receptor-binding motif of the receptor-binding domain, which is mostly due to a mutation causing an E484K”
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In the paper
“We found that the resistance of B.1.1.7 to most NTD-directed monoclonal antibodies is largely conferred by ΔY144, whereas the resistance of B.1.351 is largely conferred by Δ242-Δ244 and/or R246I.”
§ Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7 > Monoclonal antibodies
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In the paper
“The activity of CB6 is rendered inactive against B.1.351because of the K417N substitution.”
§ Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7 > Extended Data
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“Moreover, compared to wild-type SARS-CoV-2, B.1.351 is markedly more resistant to neutralization by convalescent plasma (9.4-fold) and sera from individuals who have been vaccinated (10.3-12.4-fold).”
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“We found that the resistance of B.1.1.7 to most NTD-directed monoclonal antibodies is largely conferred by ΔY144, whereas the resistance of B.1.351 is largely conferred by Δ242-Δ244 and/or R246I.”
§ Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7 > Monoclonal antibodies
plaindirect- Asserted: passes — The authors put it forward as true.
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- It may state two separate claims as one. 12
- Probably not a substantial claim. 12
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In the paper
“Eight samples show a decrease of more than 2.5-fold in neutralizing activity against B.1.1.7Δ8,in contrast to the results for neutralization of B.1.1.7.”
§ Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7 > Convalescent plasma
plainn = 8- Asserted: passes — The authors put it forward as true.
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In the paper
“Figure 3a shows that most (16 out of 20) plasma samples lost more than 2.5-fold neutralizing activity against B.1.351,while maintaining activity against B.1.1.7.”
§ Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7 > Convalescent plasma
plainn = 20- Asserted: passes — The authors put it forward as true.
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In the paper
“Brii-196 and COV2-2130 are essentially unaffected by the new variants; the activities of Brii-198 and COV2-2196 are diminished by 14.6-fold and 6.3-fold, respectively, against B.1.351but not against B.1.1.7.”
§ Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7 > Extended Data
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In the paper
“Although S309 and the combination of Brii-196 and Brii-198 are not significantly impaired, their potencies are noticeably lower”
§ Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7 > Extended Data
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Although REGN10933 and REGN10987 and COV2-2196 and COV2-2130 are seemingly unaffected against variant pseudoviruses, there are noticeable decreases in their activity against the B.1.351authentic virus.”
§ Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7 > Extended Data
hedgeddirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“B.1.351and emergent variants 13,14 with similar mutations in the spike protein present new challenges for monoclonal antibody therapies and threaten the protective efficacy of current vaccines.”
What the sources say
- Not checked yetcites [13] Faria, N. R. et al. Genomic characterisation of an emergent SARS-CoV-2 lineage in Manaus: preliminary findings. Preprint at https://virological.org/t/genomic-characterisation-of-an-emergent-sars-cov-2-lineage-in-manaus-preliminary-findings/586 (2021).
- Not checked yetcites [14] Naveca, F. et al. Phylogenetic relationship of SARS-CoV-2 sequences from Amazonas with emerging Brazilian variants harboring mutations E484K and N501Y in the spike protein. Preprint at https://virological.org/t/phylogenetic-relationship-of-sars-cov-2-sequences-from-amazonas-with-emerging-brazilian-variants-harboring-mutations-e484k-and-n501y-in-the-spike-protein/585 (2021).
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Rests on an assumption: In vitro neutralization by monoclonal antibodies predicts clinical therapeutic efficacy.
- Rests on an assumption: In vitro neutralization by vaccinee sera predicts vaccine protective efficacy.
In the paper
“These discrepant results highlight a previous observation 20 that pseudovirus neutralization does not always faithfully”
§ Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7 > Convalescent plasma
What the sources say
- Not checked yetcites [20] Liu, L. et al. Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike. Nature 584, 450–456 (2020). source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“All cell lines were obtained from authenticated vendors.”
§ Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7 > Additional information
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“The study protocol was approved by the CUIMC Institutional Review Board (IRB) and all participants provided written informed consent.”
§ Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7 > Additional information
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“No statistical methods were used to predetermine sample size.”
§ Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7 > Additional information
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Viability was measured and found to be >90%.”
§ Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7 > Additional information
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“The experiments were not randomized and the investigators were not blinded to allocation during experiments and outcome assessment.”
- Also stated in: § Additional information · plain
“Randomization is not relevant as this is an observational study.”
- Also stated in: § Additional information · plain
“The investigators were not blinded as this is an observational study.”
§ Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7 > Additional information
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Also stated in: § Additional information · plain
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“If the rampant spread of the virus continues and more critical mutations accumulate, then we may be condemned to chasing after the evolving SARS-CoV-2 continually, as we have long done for influenza virus.”
§ Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7 > Discussion
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In the paper
“Mycoplasma is negative (Detected mycoplasma contamination using Mycoplasma PCR ELISA ,Sigma,catalog number is 11663925910)”
§ Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7 > Additional information
plain- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“As for the ramifications of our findings for the protective efficacy of current SARS-CoV-2 vaccines, the neutralizing activity of sera from vaccinated individuals against B.1.1.7 is largely intact and no adverse effects on current vaccines are expected (Fig. 4c), consistent with conclusions that were reached by other studies 34,40,41 .”
§ Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7 > Discussion
What the sources say
- Not checked yetcites [34] Wu, K. et al. mRNA-1273 vaccine induces neutralizing antibodies against spike mutants from global SARS-CoV-2 variants. Preprint at https://doi.org/10.1101/2021.01.25.427948 (2021). source
- Not checked yetcites [40] Collier, D. et al. SARS-CoV-2 B.1.1.7 sensitivity to mRNA vaccine-elicited, convalescent and monoclonal antibodies. Preprint at https://doi.org/10.1101/2021.01.19.21249840 (2021). source
- Not checked yetcites [41] Muik, A. et al. Neutralization of SARS-CoV-2 lineage B.1.1.7 pseudovirus by BNT162b2 vaccine-elicited human sera. Science https://doi.org/10.1126/science.abg6105 (2021). source
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Rests on an assumption: In vitro neutralization by vaccinee sera predicts vaccine protective efficacy.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Studies that were repeated are noted in figure captions and include all studies that demonstrated the key results reported in the manuscript.”
§ Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7 > Additional information
plain- Asserted: passes — The authors put it forward as true.
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“No data were excluded from the analysis”
§ Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7 > Additional information
plain- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“E484K causes not only steric clashes but also a charge change at antibody-binding sites, and thus abolishes binding by these RBM-directed monoclonal antibodies.”
§ Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7 > Extended Data
plaindirect- Asserted: passes — The authors put it forward as true.
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Cytopathogenic effects of viral infection were visually scored for each well in a blinded manner by two independent observers.”
§ Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7 > Additional information
plain- Asserted: passes — The authors put it forward as true.
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The sample size is appropriate within technical capability to compare the difference between groups”
§ Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7 > Additional information
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“A total of 18 mutant pseudoviruses were made as previously described 20,21 , and each was found to have a robust titre (Extended Data Fig. 1c) that was adequate for neutralization studies.”
§ Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7 > Nature | Vol 593 | 6 May 2021 | 131
What the sources say
- Not checked yetcites [20] Liu, L. et al. Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike. Nature 584, 450–456 (2020). source
- Not checked yetcites [21] Wang, P. et al. SARS-CoV-2 neutralizing antibody responses are more robust in patients with severe disease. Emerg. Microbes Infect. 9, 2091–2093 (2020). source
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
The paper relies on this without support.
In vitro neutralization by monoclonal antibodies predicts clinical therapeutic efficacy.
“These findings suggest that antibody treatment of this virus might need to be modified in localities in which B.1.351and related variants 13,14 are prevalent”
“Decisions on the use of these monoclonal antibodies will depend heavily on the local prevalence of B.1.351or variants with an E484K substitution”
The paper relies on this without support.
In vitro neutralization by vaccinee sera predicts vaccine protective efficacy.
“the neutralizing activity of sera from vaccinated individuals against B.1.1.7 is largely intact and no adverse effects on current vaccines are expected”
“threaten the protective efficacy of current vaccines”
The paper relies on this without support.
Reduced neutralization of a variant by antibodies in vitro reflects reduced antibody-mediated protection against that variant in vivo.
“Overall, the neutralizing activity against B.1.1.7 was essentially unchanged, but significantly lower against B.1.351(12.4-fold for the Moderna vaccine; 10.3-fold for the Pfizer vaccine).”
The paper relies on this without support.
The convalescent plasma samples and vaccinee sera studied are representative of convalescent patients and of vaccine recipients generally.
“B.1.351 is more resistant to neutralization by convalescent plasma from patients.”
“B.1.351 is more resistant to neutralization by sera from individuals vaccinated with the Moderna or Pfizer vaccine.”
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?
The cited source says what the claim attributes to it.
In the citing paper
“As previously reported, bamlanivimab and etesivimab did not neutralize the Beta variant 21 .”
From Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization (2021) · cites this paper as [21]
In the citing paper
“Several of the RBD mutations directly affect angiotensin-converting enzyme 2 (ACE2) receptor-binding affinity, which may affect infectivity, viral load, or transmissibility.11, 12, 13, 14”
From Impact of SARS-CoV-2 variants on the total CD4+ and CD8+ T cell reactivity in infected or vaccinated individuals (2021) · cites this paper as [14]
In the citing paper
“Conversely, vaccine efficacy against B.1.1.7 is maintained (Wang et al., 2021; Emary et al., 2021; Supasa et al., 2021).”
From Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum (2021) · cites this paper as Wang et al., 2021
In the citing paper
“The Moderna mRNA-1273 vaccine also induces neutralizing antibodies to SARS-CoV-2 variants with, however, a five-to ten-fold reduction in efficacy against the B.1.351S protein, when compared to pseudovirus bearing the D614G mutation 27,28 .”
From Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing antibodies (2021) · cites this paper as [27]
In the citing paper
“The Pfizer Cominarty (also termed BNT162b2) vaccine-elicited human sera neutralizes SARS-CoV-2 lineage B.1.1.7 pseudovirus, with slightly reduced titers in some vaccinees, when compared to the Wuhan reference strain 26,27 .”
From Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing antibodies (2021) · cites this paper as [27]
In the citing paper
“The Alpha variant is susceptible to neutralization by most neutralizing mAbs as well as by most plasma samples from previously infected persons 97,102,121,149,159,[203][204][205][206] (fIg.5).”
From The biological and clinical significance of emerging SARS-CoV-2 variants (2021) · cites this paper as [121]
In the citing paper
“E484K has resulted in 3-fold to 10-fold reduced susceptibility to about 30% and >10-fold reduced susceptibility to about 10% of convalescent plasma samples”
From The biological and clinical significance of emerging SARS-CoV-2 variants (2021) · cites this paper as [121]
In the citing paper
“The Alpha variant has displayed 3-fold to 10-fold reduced susceptibility to approximately 15% of plasma samples from recipients of an authorized mRNA vaccine 97,102,121,148,149,152,159,204,208,209 .”
From The biological and clinical significance of emerging SARS-CoV-2 variants (2021) · cites this paper as [121]
In the citing paper
“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 [121]
In the citing paper
“In multiple studies, B.1.351 was the most resistant to neutralization by convalescent or vaccinee sera, with 6- to 15-fold less neutralization activity for sera from individuals immunized with vaccines based on the virus strain first described in January 2020 (Wuhan-Hu-1, spike also called WA1) (2–9).”
From Durability of mRNA-1273 vaccine–induced antibodies against SARS-CoV-2 variants (2021) · cites this paper as [5]
In the citing paper
“Most of these prior studies have evaluated sera from vaccinated individuals at time points soon after the first or second dose and have had limited data on the durability of such responses.”
From Durability of mRNA-1273 vaccine–induced antibodies against SARS-CoV-2 variants (2021) · cites this paper as [5]
In the citing paper
“However, reduced sensitivity of SARS-CoV-2 variants to antibody and serum neutralization has been widely observed (18–21).”
From Deep learning guided optimization of human antibody against SARS-CoV-2 variants with broad neutralization (2022) · cites this paper as [21]
In the citing paper
“Beta [as a benchmark for partially reduced neutralization (7) without major impact on effectiveness (19, 20)]”
From Neutralization of SARS-CoV-2 Omicron by BNT162b2 mRNA vaccine–elicited human sera (2022) · cites this paper as [7]
In the citing paper
“Some amino acid changes [Δ69/70, T95I, G142D, Δ145, K417N, T478K, N501Y, and P681H (T, Thr; I, Ile; G, Gly; D, Asp; K, Lys; N, Asn; Y, Tyr; P, Pro; H, His)] are shared mutations also found in the Alpha, Beta (B.1.351), Gamma (P.1), or Delta VOCs and were described to lead to increased transmissibility, as well as to a typically mild partial escape from vaccine-induced humoral immunity (7–10).”
From Neutralization of SARS-CoV-2 Omicron by BNT162b2 mRNA vaccine–elicited human sera (2022) · cites this paper as [7]
In the citing paper
“Several SARS-CoV-2 variants of concern have emerged that display increased transmissibility or reduced in-vitro neutralisation by sera from people who are infected with the ancestral strain or immunised.2, 3, 4”
From Neutralising antibody titres as predictors of protection against SARS-CoV-2 variants and the impact of boosting: a meta-analysis (2022) · cites this paper as [2]
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Metadata
- Authors
- Wang, P., Nair, M. S., Liu, L., Iketani, S., Luo, Y., Guo, Y., Wang, M., Yu, J., Zhang, B., Kwong, P. D., Graham, B. S., Mascola, J. R., Chang, J. Y., Yin, M. T., Sobieszczyk, M., Kyratsous, C. A., Shapiro, L., Sheng, Z., Huang, Y., & Ho, D. D.
- Affiliations
- Aaron Diamond AIDS Research Center (US)
- National Institutes of Health (US)
- Regeneron (United States) (US)
- Corresponding author
- Huang, Yaoxing
- Ho, David D.
- ORCID
- Venue
- Nature
- Published
- 2021-03-08
- Volume
- 593
- Issue
- 7857
- Pages
- 130-135
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC7852232
- OpenAlex
- W3123551159
- Cited by
- 2,312
- References
- 51
- Citations by year
- 2026: 34 · 2025: 101 · 2024: 136 · 2023: 299 · 2022: 750 · 2021: 984
- FWCI
- 171.98
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nature (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- Research Square (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion, cc-by)
- PubMed Central (submittedVersion, cc-by-nc-nd)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Bill and Melinda Gates Foundation
- JPB Foundation
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- SARS-CoV-2, SARS-CoV-2 variants, Beta variant, Alpha variant, antibody resistance, neutralizing antibodies, monoclonal antibodies, spike protein mutations, N-terminal domain, receptor binding domain, convalescent plasma, vaccine efficacy
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.
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