Neutralization of SARS-CoV-2 Omicron by BNT162b2 mRNA vaccine–elicited human sera
Open accessPublished version of a preprint
Abstract
The globally circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of concern Omicron (B.1.1.529) has a large number of mutations, especially in the spike protein, indicating that recognition by neutralizing antibodies may be compromised. We tested Wuhan (Wuhan-Hu-1 reference strain), Beta (B.1.351), Delta (B.1.617.2), or Omicron pseudoviruses with sera of 51 participants who received two or three doses of the messenger RNA (mRNA)–based COVID-19 vaccine BNT162b2. After two doses, Omicron-neutralizing titers were reduced >22-fold compared with Wuhan-neutralizing titers. One month after the third vaccine dose, Omicron-neutralizing titers were increased 23-fold relative to their levels after two doses and were similar to levels of Wuhan-neutralizing titers after two doses. The requirement of a third vaccine dose to effectively neutralize Omicron was confirmed with sera from a subset of participants using live SARS-CoV-2. These data suggest that three doses of the mRNA vaccine BNT162b2 may protect against Omicron-mediated COVID-19.
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Written from the paper’s full text.
TL;DR
Two doses of BNT162b2 elicited substantially reduced neutralizing activity against SARS-CoV-2 Omicron, while a third dose boosted Omicron-neutralizing titers to levels comparable to Wuhan-neutralizing titers after two doses in the pseudovirus assay. The data suggest that three BNT162b2 doses may protect against Omicron-mediated COVID-19.
Key findings
- After two BNT162b2 doses, Omicron pseudovirus-neutralizing GMTs were 7 versus 160 for Wuhan, a 22.8-fold reduction; 20 of 32 sera had no detectable Omicron neutralization. Beta and Delta GMTs were 24 and 73, corresponding to 6.7- and 2.2-fold reductions versus Wuhan.
- One month after a third dose, Omicron pseudovirus-neutralizing GMTs rose to 164, a 23.4-fold increase over post-dose-two levels and similar to Wuhan GMTs after two doses (160); 29 of 30 sera neutralized Omicron. Beta, Delta, and Wuhan GMTs after dose three were 279, 413, and 368.
- In live SARS-CoV-2 assays, two doses gave Omicron GMTs of 6 versus 368 for Wuhan, a 61.3-fold reduction, with 17 of 25 sera showing no detectable Omicron neutralization. After a third dose, Omicron GMTs increased 17.6-fold to 106 and remained 3.4-fold lower than Wuhan GMTs after two doses; 27 of 28 sera neutralized live Omicron.
- Among 244 HLA class I–restricted Wuhan S epitopes from IEDB, 85.3% (208) were unaffected at the amino acid sequence level in Omicron.
Methods
- Pseudovirus-neutralization tests used VSV-SARS-CoV-2-S pseudoviruses bearing Wuhan, Omicron, Beta, or Delta S proteins with sera from 32 BNT162-01 participants 21 days after dose two and 30 BNT162-14/BNT162-17 participants 1 month after dose three; 11 participants were analyzed longitudinally.
- Live SARS-CoV-2 neutralization tests used Wuhan and Omicron virus with sera from 32 and 25 participants after dose two, respectively, and 7 and 28 participants after dose three, respectively. Specimens were tested in duplicate and geometric mean 50% neutralizing titers were calculated.
- T cell analysis assessed 244 HLA class I–restricted S epitopes reported in IEDB for conservation in Omicron.
Limitations
- The paper states that serum panels came from different clinical trials with limited sample size, and the interval between second and third doses was not consistent across participants.
- The paper states that future analyses are needed to evaluate antibody persistence, and notes that a longer interval (>42 days) between first and second doses may improve immunogenicity but was not evaluated here.
- Evident from the text: the study reports neutralization titers, not clinical efficacy; live Omicron testing used smaller subsets than pseudovirus testing; and durability beyond 1 month after the third dose was not assessed.
Model-written summary. Check it against the paper before relying on it.
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- Findingown data
One month after the third BNT162b2 dose, live Omicron neutralizing GMTs were reduced 3.4-fold compared with Wuhan reference at 21 days after two doses (GMT 106 vs 368).
“and were reduced 3.4-fold compared with those against the Wuhan reference at 21 days after two doses of BNT162b2 (GMT of 106 versus 368).”
Quote in the paperSubstantial claim- Rests on an assumption: Sera from different clinical trials are comparable for neutralizing antibody analysis.
- Findingown data
Twenty-nine of 30 serum specimens after the third dose were capable of neutralizing Omicron pseudovirus.
“Twenty-nine of 30 serum specimens were capable of neutralizing the Omicron pseudovirus (table S3).”
Quote in the paperSubstantial claim - Findingown data
After two doses of BNT162b2, geometric mean neutralization titers (GMTs) against Omicron pseudovirus were reduced 22.8-fold compared with Wuhan reference pseudovirus (GMT 7 vs 160).
“After two doses of BNT162b2, geometric mean neutralization titers (GMTs) against Omicron pseudovirus were reduced 22.8-fold compared with those for the Wuhan reference pseudovirus (Fig. 1; GMT of 7 versus 160).”
Quote in the paperSubstantial claim - Findingown data
One month after the third BNT162b2 dose, neutralizing GMTs against Omicron pseudovirus increased 23.4-fold relative to their levels 21 days after the second dose (GMT 164 vs 7).
“One month after the third BNT162b2 dose, neutralizing GMTs against the Omicron variant pseudovirus increased 23.4-fold relative to their levels 21 days after the second dose (GMT of 164 versus 7)”
Quote in the paperSubstantial claim - Findingown data
Twenty of 32 immune serum specimens after two doses displayed no detectable neutralizing activity against Omicron pseudovirus.
“Twenty of 32 immune serum specimens displayed no detectable neutralizing activity against Omicron (table S2).”
Quote in the paperSubstantial claim
- Findingown data
Neutralizing GMTs against live SARS-CoV-2 Omicron were reduced 61.3-fold relative to Wuhan reference strain (GMT 6 vs 368) at 21 days after two doses.
“Neutralizing GMTs against live SARS-CoV-2 Omicron were reduced 61.3-fold relative to those against the Wuhan reference strain (Fig. 2; GMT of 6 versus 368) at 21 days after two doses of BNT162b2.”
Quote in the paperSubstantial claim - Findingown data
In 11 individuals, 21 days after dose two, sera exhibited a 21.4-fold reduction in GMT against Omicron pseudovirus compared with Wuhan reference (GMT 7 vs 150).
“Twenty-one days after dose two, sera exhibited a 21.4-fold reduction in GMT against the Omicron variant compared with the Wuhan reference pseudovirus (fig. S1; GMT of 7 versus 150).”
Quote in the paperSubstantial claim - Findingown data
One month after the third BNT162b2 dose, neutralizing GMTs against live Omicron were increased 17.6-fold compared with neutralizing GMTs at 21 days after the second dose (GMT 106 vs 6).
“One month after the third BNT162b2 dose, neutralizing GMTs against Omicron were increased 17.6-fold compared with neutralizing GMTs at 21 days after the second dose (GMT of 106 versus 6)”
Quote in the paperSubstantial claim - Findingown data
Seventeen of 25 serum specimens after two doses displayed no detectable neutralizing activity against live Omicron.
“Seventeen of 25 serum specimens displayed no detectable neutralizing activity against Omicron (table S4).”
Quote in the paperSubstantial claim - Findingown data
One month after the third BNT162b2 dose, Omicron pseudovirus neutralizing GMTs were comparable to Wuhan pseudovirus neutralizing GMTs at 21 days after two doses (GMT 164 vs 160).
“and were comparable to neutralizing GMTs against the reference Wuhan pseudovirus at 21 days after two doses of BNT162b2 (GMT of 164 versus 160).”
Quote in the paperSubstantial claim- Rests on an assumption: Sera from different clinical trials are comparable for neutralizing antibody analysis.
- Findingown data
The observed SARS-CoV-2-neutralizing GMTs correlated positively with the neutralizing GMTs against VSV-SARS-CoV-2-S pseudoviruses.
“The observed SARS-CoV-2–neutralizing GMTs correlated positively with the neutralizing GMTs against VSV-SARS-CoV-2-S pseudoviruses (fig. S2).”
Quote in the paperNot a substantial claim - Findingown data
85.3% (208 of 244) of described human leukocyte antigen class I-restricted T cell epitopes from the Wuhan S protein sequence were not affected on the amino acid sequence level in Omicron.
“Despite the multitude of mutations in the Omicron S protein, 85.3% (n = 208) of the described class I epitopes were not affected on the amino acid sequence level”
Quote in the paperSubstantial claim - Findingown data
Twenty-seven of 28 post-dose three serum specimens neutralized live SARS-CoV-2 Omicron.
“Twenty-seven of 28 post–dose three serum specimens neutralized live SARS-CoV-2 Omicron (table S5).”
Quote in the paperSubstantial claim - Study design and conductcitation
The pseudovirus-neutralization test (pVNT) has been shown to be in close concordance with live SARS-CoV-2-neutralization assays.
“a pseudovirus-neutralization test (pVNT) that has been shown to be in close concordance with live SARS-CoV-2–neutralization assays (17, 18)”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [17] J. B. Case, P. W. Rothlauf, R. E. Chen, Z. Liu, H. Zhao, A. S. Kim, L.-M. Bloyet, Q. Zeng, S. Tahan, L. Droit, M. X. G. Ilagan, M. A. Tartell, G. Amarasinghe, J. P. Henderson, S. Miersch, M. Ustav, S. Sidhu, H. W. Virgin, D. Wang, S. Ding, D. Corti, E. S. Theel, D. H. Fremont, M. S. Diamond, S. P. J. Whelan, Neutralizing Antibody and Soluble ACE2 Inhibition of a Replication-Competent VSV-SARS-CoV-2 and a Clinical Isolate of SARS-CoV-2. Cell Host Microbe 28, 475– 485.e5 (2020). 10.1016/j.chom.2020.06.021 32735849 PMC7332453 source
Not checked in the free run.
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Not checked in the free run.
- Premisecitation
BNT162b2 contains lipid nanoparticle-formulated mRNA encoding the SARS-CoV-2 S glycoprotein from the Wuhan-Hu-1 reference strain.
“The BNT162b2 COVID-19 mRNA vaccine contains lipid nanoparticle–formulated mRNA that encodes the SARS-CoV-2 S glycoprotein from the parental Wuhan reference strain (Wuhan-Hu-1) (11).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [11] U. Sahin, A. Muik, I. Vogler, E. Derhovanessian, L. M. Kranz, M. Vormehr, J. Quandt, N. Bidmon, A. Ulges, A. Baum, K. E. Pascal, D. Maurus, S. Brachtendorf, V. Lörks, J. Sikorski, P. Koch, R. Hilker, D. Becker, A.-K. Eller, J. Grützner, M. Tonigold, C. Boesler, C. Rosenbaum, L. Heesen, M.-C. Kühnle, A. Poran, J. Z. Dong, U. Luxemburger, A. Kemmer-Brück, D. Langer, M. Bexon, S. Bolte, T. Palanche, A. Schultz, S. Baumann, A. J. Mahiny, G. Boros, J. Reinholz, G. T. Szabó, K. Karikó, P.-Y. Shi, C. Fontes-Garfias, J. L. Perez, M. Cutler, D. Cooper, C. A. Kyratsous, P. R. Dormitzer, K. U. Jansen, Ö. source
Not checked in the free run.
- Premisecitation
Neutralizing antibody titers are strongly predictive of the degree of immune protection against symptomatic SARS-CoV-2 infection.
“Because neutralizing antibody titers are strongly predictive of the degree of immune protection against symptomatic SARS-CoV-2 infection (16)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [16] D. S. Khoury, D. Cromer, A. Reynaldi, T. E. Schlub, A. K. Wheatley, J. A. Juno, K. Subbarao, S. J. Kent, J. A. Triccas, M. P. Davenport, Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nat. Med. 27, 1205– 1211 (2021). 10.1038/s41591-021-01377-8 34002089 source
Not checked in the free run.
- Study design and conductcitation
The study used two orthogonal test systems: a pseudovirus-neutralization test and a live SARS-CoV-2-neutralization test.
“we used two orthogonal test systems: a pseudovirus-neutralization test (pVNT) that has been shown to be in close concordance with live SARS-CoV-2–neutralization assays (17, 18), as well as a live SARS-CoV-2–neutralization test (VNT).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [17] J. B. Case, P. W. Rothlauf, R. E. Chen, Z. Liu, H. Zhao, A. S. Kim, L.-M. Bloyet, Q. Zeng, S. Tahan, L. Droit, M. X. G. Ilagan, M. A. Tartell, G. Amarasinghe, J. P. Henderson, S. Miersch, M. Ustav, S. Sidhu, H. W. Virgin, D. Wang, S. Ding, D. Corti, E. S. Theel, D. H. Fremont, M. S. Diamond, S. P. J. Whelan, Neutralizing Antibody and Soluble ACE2 Inhibition of a Replication-Competent VSV-SARS-CoV-2 and a Clinical Isolate of SARS-CoV-2. Cell Host Microbe 28, 475– 485.e5 (2020). 10.1016/j.chom.2020.06.021 32735849 PMC7332453 source
Not checked in the free run.
- cites [18] A. B. Vogel, I. Kanevsky, Y. Che, K. A. Swanson, A. Muik, M. Vormehr, L. M. Kranz, K. C. Walzer, S. Hein, A. Güler, J. Loschko, M. S. Maddur, A. Ota-Setlik, K. Tompkins, J. Cole, B. G. Lui, T. Ziegenhals, A. Plaschke, D. Eisel, S. C. Dany, S. Fesser, S. Erbar, F. Bates, D. Schneider, B. Jesionek, B. Sänger, A.-K. Wallisch, Y. Feuchter, H. Junginger, S. A. Krumm, A. P. Heinen, P. Adams-Quack, J. Schlereth, S. Schille, C. Kröner, R. de la Caridad Güimil Garcia, T. Hiller, L. Fischer, R. S. Sellers, S. Choudhary, O. Gonzalez, F. Vascotto, M. R. Gutman, J. A. Fontenot, S. Hall-Ursone, K. Brasky, M source
Not checked in the free run.
- Interpretationown data
A third dose of BNT162b2 boosts Omicron-neutralization capability to robust levels.
“Both assays also showed that a third dose of BNT162b2 boosts Omicron-neutralization capability to robust levels.”
Quote in the paperSubstantial claim - Interpretationown data
CD8+ T cell recognition of Omicron S glycoprotein epitopes is largely preserved.
“our analyses suggest that CD8+ T cell recognition of Omicron S glycoprotein epitopes is largely preserved.”
Quote in the paperSubstantial claim- Rests on an assumption: Class I epitopes that are unchanged at the amino acid sequence level remain recognized by vaccine-elicited CD8+ T cells.
- Interpretationown data
A third dose of BNT162b2 augments antibody-based immunity against Omicron.
“demonstrate that a third dose of BNT162b2 augments antibody-based immunity against Omicron”
Quote in the paperSubstantial claim - Interpretationown data
The requirement of a third vaccine dose to effectively neutralize Omicron was confirmed with sera from a subset of participants using live SARS-CoV-2.
“The requirement of a third vaccine dose to effectively neutralize Omicron was confirmed with sera from a subset of participants using live SARS-CoV-2.”
Quote in the paperSubstantial claim - Premisecitation
BNT162b2 vaccination induces strong polyepitopic T cell responses directed against multiple epitopes spanning the length of the S protein.
“BNT162b2 vaccination induces strong polyepitopic T cell responses, directed against multiple epitopes spanning the length of the S protein (11).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [11] U. Sahin, A. Muik, I. Vogler, E. Derhovanessian, L. M. Kranz, M. Vormehr, J. Quandt, N. Bidmon, A. Ulges, A. Baum, K. E. Pascal, D. Maurus, S. Brachtendorf, V. Lörks, J. Sikorski, P. Koch, R. Hilker, D. Becker, A.-K. Eller, J. Grützner, M. Tonigold, C. Boesler, C. Rosenbaum, L. Heesen, M.-C. Kühnle, A. Poran, J. Z. Dong, U. Luxemburger, A. Kemmer-Brück, D. Langer, M. Bexon, S. Bolte, T. Palanche, A. Schultz, S. Baumann, A. J. Mahiny, G. Boros, J. Reinholz, G. T. Szabó, K. Karikó, P.-Y. Shi, C. Fontes-Garfias, J. L. Perez, M. Cutler, D. Cooper, C. A. Kyratsous, P. R. Dormitzer, K. U. Jansen, Ö. source
Not checked in the free run.
- Interpretationown data
Two doses of the BNT162b2 mRNA vaccine may not be sufficient to protect against infection with the Omicron variant.
“In summary, our data indicate that two doses of the BNT162b2 mRNA vaccine may not be sufficient to protect against infection with the Omicron variant.”
Quote in the paperSubstantial claim - Interpretationown data
The overall trends between pseudovirus and live virus neutralization assays are similar.
“Notably, the overall trends are similar”
Quote in the paperNot a substantial claim - Interpretationown data
The targets of most T cell responses elicited by BNT162b2 may still be conserved in the Omicron variant.
“indicating that the targets of most T cell responses elicited by BNT162b2 may still be conserved in the Omicron variant (fig. S3).”
Quote in the paperSubstantial claim - Interpretationown data
A third BNT162b2 dose effectively neutralizes Omicron at a similar order of magnitude to that observed for wild-type SARS-CoV-2 after two doses of BNT162b2.
“Our data show that a third BNT162b2 dose effectively neutralizes Omicron at a similar order of magnitude to that observed for wild-type SARS-CoV-2 after two doses of BNT162b2.”
Quote in the paperSubstantial claim- Rests on an assumption: Sera from different clinical trials are comparable for neutralizing antibody analysis.
- May combine two claims. 9
- Classified as probably not a substantial claim. 7
May combine two claims.
Findingown dataThe majority of sera after two doses neutralized Beta and Delta pseudoviruses with GMTs of 24 and 73, respectively, corresponding to 6.7- and 2.2-fold reductions compared with Wuhan pseudovirus.
“By contrast, the majority of sera neutralized Beta and Delta pseudoviruses with GMTs of 24 and 73, respectively. This corresponds to 6.7- and 2.2-fold reductions in neutralization activity compared with the Wuhan pseudovirus”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThe third dose of BNT162b2 resulted in a significant increase in neutralizing titers against Wuhan pseudovirus (GMT 320) and a 25.8-fold increase in neutralizing titers against Omicron 1 month after dose three compared with 21 days after dose two (GMT 181 vs 7).
“the third dose of BNT162b2 resulted in a significant increase in neutralizing titers against the Wuhan pseudovirus (GMT of 320) and a 25.8-fold increase in neutralizing titers against Omicron 1 month after dose three compared with 21 days after dose two (GMT of 181 versus 7).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataBefore receiving the third dose (median 256 days after dose two), neutralizing titers against Wuhan pseudovirus were considerably reduced (GMT 13), whereas Omicron-specific titers were below the limit of detection.
“Before receiving the third dose of BNT162b2 (at a median 256 days after dose two), neutralizing titers against the Wuhan pseudovirus were considerably reduced (GMT of 13), whereas the Omicron-specific titers were below the limit of detection.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThe third dose of BNT162b2 increased neutralizing activity against Beta, Delta, and Wuhan pseudoviruses, with GMTs of 279, 413, and 368, respectively.
“The third dose of BNT162b2 also increased neutralizing activity against Beta, Delta, and Wuhan pseudoviruses, with GMTs of 279, 413, and 368, respectively.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
PremisecitationThe receptor binding domain and N-terminal domain are immunodominant targets of neutralizing antibodies elicited by COVID-19 vaccines or SARS-CoV-2 infection.
“both being immunodominant targets of neutralizing antibodies elicited by COVID-19 vaccines or by SARS-CoV-2 infection (5, 6).”
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Not checked in the free run.
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Not checked in the free run.
May combine two claims.
PremisecitationBNT162b2 elicits strong antibody responses that effectively neutralize the parental strain and diverse SARS-CoV-2 VOCs.
“and to elicit strong antibody responses, effectively neutralizing the parental strain as well as diverse SARS-CoV-2 VOCs (13–15).”
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Not checked in the free run.
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Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationTwo 30-μg doses of BNT162b2 had 95% efficacy in a phase 3 trial.
“Administration of two 30-μg doses of BNT162b2 was shown to have 95% efficacy in a phase 3 trial (12)”
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Not checked in the free run.
May combine two claims.
PremisecitationFifteen mutations are located in the receptor binding domain and eight mutated sites in the N-terminal domain of the Omicron spike protein.
“Fifteen mutations are located in the receptor binding domain and another eight mutated sites are found in the N-terminal domain”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [4] WHO Headquarters, WHO Health Emergencies Programme, “Enhancing Readiness for Omicron (B.1.1.529): Technical Brief and Priority Actions for Member States” (2021); www.who.int/publications/m/item/enhancing-readiness-for-omicron-(b.1.1.529)-technical-brief-and-priority-actions-for-member-states.
Not checked in the free run.
May combine two claims.
PremisecitationSome amino acid changes shared with Alpha, Beta, Gamma, or Delta VOCs lead to increased transmissibility and partial escape from vaccine-induced humoral immunity.
“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).”
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Not checked in the free run.
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- cites [9] Q. Wang, M. S. Nair, S. Anang, S. Zhang, H. Nguyen, Y. Huang, L. Liu, D. D. Ho, J. G. Sodroski, Functional differences among the spike glycoproteins of multiple emerging severe acute respiratory syndrome coronavirus 2 variants of concern. iScience 24, 103393 (2021). 10.1016/j.isci.2021.103393 34746689 PMC8559451 source
Not checked in the free run.
- cites [10] A. J. Greaney, T. N. Starr, P. Gilchuk, S. J. Zost, E. Binshtein, A. N. Loes, S. K. Hilton, J. Huddleston, R. Eguia, K. H. D. Crawford, A. S. Dingens, R. S. Nargi, R. E. Sutton, N. Suryadevara, P. W. Rothlauf, Z. Liu, S. P. J. Whelan, R. H. Carnahan, J. E. Crowe Jr., J. D. Bloom, Complete Mapping of Mutations to the SARS-CoV-2 Spike Receptor-Binding Domain that Escape Antibody Recognition. Cell Host Microbe 29, 44– 57.e9 (2021). 10.1016/j.chom.2020.11.007 33259788 PMC7676316 source
Not checked in the free run.
May combine two claims.
PremisecitationOmicron is a highly divergent variant and harbors a previously unseen number of mutations in its spike glycoprotein.
“Omicron is a highly divergent variant and harbors a previously unseen number of mutations in its spike (S) glycoprotein (4).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [4] WHO Headquarters, WHO Health Emergencies Programme, “Enhancing Readiness for Omicron (B.1.1.529): Technical Brief and Priority Actions for Member States” (2021); www.who.int/publications/m/item/enhancing-readiness-for-omicron-(b.1.1.529)-technical-brief-and-priority-actions-for-member-states.
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationBeta is a benchmark for partially reduced neutralization without major impact on effectiveness.
“Beta [as a benchmark for partially reduced neutralization (7) without major impact on effectiveness (19, 20)]”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [7] P. Wang, M. S. Nair, L. Liu, S. Iketani, Y. Luo, Y. Guo, M. Wang, J. Yu, B. Zhang, P. D. Kwong, B. S. Graham, J. R. Mascola, J. Y. Chang, M. T. Yin, M. Sobieszczyk, C. A. Kyratsous, L. Shapiro, Z. Sheng, Y. Huang, D. D. Ho, Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7. Nature 593, 130– 135 (2021). 10.1038/s41586-021-03398-2 33684923 source
Not checked in the free run.
- cites [19] L. J. Abu-Raddad, H. Chemaitelly, A. A. Butt; National Study Group for COVID-19 Vaccination, Effectiveness of the BNT162b2 Covid-19 Vaccine against the B.1.1.7 and B.1.351 Variants. N. Engl. J. Med. 385, 187– 189 (2021). 10.1056/NEJMc2104974 33951357 PMC8117967 source
Not checked in the free run.
- cites [20] O. Mor, N. S. Zuckerman, I. Hazan, R. Fluss, N. Ash, N. Ginish, E. Mendelson, S. Alroy-Preis, L. Freedman, A. Huppert, BNT162b2 vaccine effectiveness was marginally affected by the SARS-CoV-2 beta variant in fully vaccinated individuals. J. Clin. Epidemiol. 142, 38– 44 (2022). 10.1016/j.jclinepi.2021.10.011 34715314 PMC8553421 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenThe analysis evaluated and compared serum panels from different clinical trials with a limited sample size.
“In the analysis presented here, we have evaluated and compared serum panels from different clinical trials with a limited sample size.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataEach specimen was tested in duplicate.
“Each specimen was tested in duplicate, and geometric mean 50% pseudovirus-neutralizing titers (GMTs) were plotted.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataThe time elapsed between the second and third doses was not consistent across participants.
“but the time elapsed between the second and third doses was not consistent across participants.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationT cell responses play a vital role as a second layer of defense, in particular in the prevention of severe COVID-19.
“T cell responses play a vital role as a second layer of defense, in particular in the prevention of severe COVID-19 (26).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [26] A. Bertoletti, N. Le Bert, M. Qui, A. T. Tan, SARS-CoV-2-specific T cells in infection and vaccination. Cell. Mol. Immunol. 18, 2307– 2312 (2021). 10.1038/s41423-021-00743-3 34471260 PMC8408362 source
Not checked in the free run.
The paper relies on this without support.
Class I epitopes that are unchanged at the amino acid sequence level remain recognized by vaccine-elicited CD8+ T cells.
“Despite the multitude of mutations in the Omicron S protein, 85.3% (n = 208) of the described class I epitopes were not affected on the amino acid sequence level, indicating that the targets of most T cell responses elicited by BNT162b2 may still be conserved in the Omicron variant (fig. S3).”
“our analyses suggest that CD8+ T cell recognition of Omicron S glycoprotein epitopes is largely preserved.”
The paper relies on this without support.
Sera from different clinical trials are comparable for neutralizing antibody analysis.
“we have evaluated and compared serum panels from different clinical trials with a limited sample size.”
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?
Neutralization titers after two doses of BNT162b2 were 160, 7, 24, and 73 GMTs for wild-type SARS-CoV-2, Omicron, Beta, and Delta variants, respectively.
“neutralization titers induced after two doses of BNT162b2 were 160, 7, 24, and 73 GMTs for wild-type SARS-CoV-2, Omicron, Beta, and Delta variants, respectively”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [406]
After one month following a booster vaccination, neutralization titers improved to 368, 164, 279, and 413 GMTs for wild-type, Omicron, Beta, and Delta, respectively.
“but improved to 368, 164, 279, and 413 GMTs, after one month following a booster vaccination.”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [406]
In multiple trials, neutralizing antibody titers after the second dose of mRNA-based vaccines were highly reduced for omicron compared with delta and especially compared with the wild-type variant, while the third dose significantly improved antibody neutralization titers.
“In all cases, neutralizing antibody titers after the second dose of mRNA-based vaccines were highly reduced for omicron (B.1.1.529) compared with delta (B.1.617.2) and especially compared with the wild-type variant, while the third dose significantly improved antibody neutralization titers.110,112,113”
From COVID-19 mRNA vaccines: Platforms and current developments (2022) · cites this paper as [113]
Comparable trends were observed in live virus neutralization testing.
“Comparable trends were observed in live virus neutralization testing.”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [406]
Booster with BNT162b2 may enhance neutralization of the Omicron variant.
“Thus vaccine booster with BNT162b2 may enhance neutralization of the Omicron variant.406”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [406]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Live-virus fold reduction does not match the reported GMTs
MinorThe reported GMTs give 368 ÷ 106 = 3.47, which rounds to a 3.5-fold reduction, not 3.4-fold. Rounding the GMTs to whole numbers cannot account for the difference.
Reported 3.4 · recomputed 3.471698
“were reduced 3.4-fold compared with those against the Wuhan reference at 21 days after two doses of BNT162b2 (GMT of 106 versus 368)”
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- Authors
- Muik, A., Lui, B. G., Wallisch, A.-K., Bacher, M., Mühl, J., Reinholz, J., Ozhelvaci, O., Beckmann, N., Güimil Garcia, R. D. L. C., Poran, A., Shpyro, S., Finlayson, A., Cai, H., Yang, Q., Swanson, K. A., Türeci, Ö., & Şahin, U.
- Affiliations
- BioNTech (Germany) (DE)
- BioNTech, An der Goldgrube 12, 55131 Mainz, Germany.
- BioNTech (United States) (US)
- Pfizer (United States) (US)
- Johannes Gutenberg University Mainz (DE)
- Corresponding author
- Şahin, Uğur
- ORCID
- Venue
- Science
- Published
- 2022-02-11
- Volume
- 375
- Issue
- 6581
- Pages
- 678-680
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC9836206
- OpenAlex
- W4205283268
- Semantic Scholar
- 31ac060c1da1a7151d25d210ffb13c5366317bbf
- Cited by
- 367
- References
- 29
- Citations by year
- 2026: 11 · 2025: 21 · 2024: 40 · 2023: 103 · 2022: 190 · 2021: 1
- FWCI
- 43.20
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Science (publishedVersion, cc-by)
- medRxiv (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Pfizer
- 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
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Keywords
- Omicron variant, BNT162b2 mRNA vaccine, neutralizing antibodies, third vaccine dose, spike protein mutations, COVID-19 protection, pseudovirus neutralization
- MeSH terms
- COVID-19, SARS-CoV-2, COVID-19 Vaccines, BNT162 Vaccine, Adolescent, Adult, Aged, Aged, 80 and over, Antibodies, Viral, Humans, Immunization Schedule, Immunization, Secondary, Middle Aged, Mutation, Neutralization Tests, T-Lymphocytes, Vaccination, Young Adult, 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.
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