Cited by 367SARS-CoV-2 and COVID-19 ResearchAnimal Virus Infections StudiesCOVID-19 Clinical Research Studies

The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index; none of the 23 sources its claims cite is checked for support yet.

Neutralization of SARS-CoV-2 Omicron by BNT162b2 mRNA vaccine–elicited human sera

Open access

Published 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.

Overview

AI snapshot

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.

Integrity signals

Registry

Crossref · 10.1126/science.abn7591

Cites

30 of 30 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

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

Show all 26 claims

  • It may state two separate claims as one. 9
  • Probably not a substantial claim. 7
15 of 15
  • 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.”
2 of 2

Claims other papers make about this one

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

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

  • Live-virus fold reduction does not match the reported GMTs

    Minor

    The 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

1 of 1

Citations

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Research works printed but not linked: 1

  1. https://doi.org/10.1101/2021.12.08.21267417.10.1101/2021.12.08.21267417 2021.12.08.21267417 · DOI · Paper page

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Metadata

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
Venue
Science
Published
2022-02-11
Volume
375
Issue
6581
Pages
678-680
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W4205283268
Cited by
367
References
29
Citations by year
2026: 11 · 2025: 21 · 2024: 40 · 2023: 103 · 2022: 190
FWCI
43.20
Type
journal article
Language
en
Open access
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

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