Cited by 919SARS-CoV-2 and COVID-19 Researchvaccines and immunoinformatics approachesImmune responses and vaccinations

The DOI matches its Crossref record; 65 of the 65 references it cites were found in a registry or an index; 36 of the 49 sources its claims cite were checked for support.

BNT162b2 vaccine induces neutralizing antibodies and poly-specific T cells in humans

Open access

Published version of a preprint

Abstract

BNT162b2, a nucleoside-modified mRNA formulated in lipid nanoparticles that encodes the SARS-CoV-2 spike glycoprotein (S) stabilized in its prefusion conformation, has demonstrated 95% efficacy in preventing COVID-19 1. Here we extend a previous phase-I/II trial report 2 by presenting data on the immune response induced by BNT162b2 prime-boost vaccination from an additional phase-I/II trial in healthy adults (18-55 years old). BNT162b2 elicited strong antibody responses: at one week after the boost, SARS-CoV-2 serum geometric mean 50% neutralizing titres were up to 3.3-fold above those observed in samples from individuals who had recovered from COVID-19. Sera elicited by BNT162b2 neutralized 22 pseudoviruses bearing the S of different SARS-CoV-2 variants. Most participants had a strong response of IFNγ+ or IL-2+ CD8+ and CD4+ T helper type 1 cells, which was detectable throughout the full observation period of nine weeks following the boost. Using peptide-MHC multimer technology, we identified several BNT162b2-induced epitopes that were presented by frequent MHC alleles and conserved in mutant strains. One week after the boost, epitope-specific CD8+ T cells of the early-differentiated effector-memory phenotype comprised 0.02-2.92% of total circulating CD8+ T cells and were detectable (0.01-0.28%) eight weeks later. In summary, BNT162b2 elicits an adaptive humoral and poly-specific cellular immune response against epitopes that are conserved in a broad range of variants, at well-tolerated doses.

Overview

Integrity signals

Registry

Crossref · 10.1038/s41586-021-03653-6

Cites

65 of 65 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

89 Own result · 21 Own method · 12 Partly supported · 6 Own interpretation · 5 Sources not found · 4 Supported · 4 Couldn’t confirm · 2 No full text of the sources · 1 Supported so far · 1 Not checked yet · 1 No basis given · accuracy not yet measured

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Show all 54 claims

  • It may state two separate claims as one. 56
  • Probably not a substantial claim. 47
92 of 92
  • The paper relies on this without support.

    The sufficiency of neutralizing antibodies alone for full and long-lasting protective immunity to SARS-CoV-2, and the contribution of SARS-CoV-2-specific T cells, remain unclear.

    “The sufficiency of neutralizing antibodies alone for full and long-lasting protective immunity to SARS-CoV-2, and the contribution of SARS-CoV-2-specific T cells, remain unclear.”
  • The paper relies on this without support.

    The convalescent serum panel is a valid comparator for judging the magnitude of vaccine-induced antibody responses.

    “Samples from individuals who had recovered from infection with SARS-CoV-2 or COVID-19 ('human convalescent samples' (HCS)) (n = 38) were obtained at least 14 days after PCR-confirmed diagnosis and at a time at which the donors were no longer symptomatic.”
  • The paper relies on this without support.

    The reporter virus's similar plaque morphology and indistinguishable growth curves from wild-type virus mean it is a valid surrogate for wild-type SARS-CoV-2 in neutralization assays.

    “The reporter virus generates similar plaque morphologies and indistinguishable growth curves from wild-type virus.”
  • The paper relies on this without support.

    The identity of the USA_WA1/2020 strain S sequence to wild-type SARS-CoV-2 S means that neutralization titers against this strain reflect neutralization of wild-type SARS-CoV-2.

    “The USA_WA1/2020 strain S is identical in sequence to the wild-type SARS-CoV-2 S (Wuhan-Hu-1 isolate).”
  • The paper relies on this without support.

    The ELISpot normalization method adequately corrects for varying sample quality.

    “To account for varying sample quality reflected in the number of spots in response to anti-CD3 antibody stimulation, we applied a normalization method that enabled direct comparison of spot counts and strength of response between individuals.”
  • The paper relies on this without support.

    The pMHC multimer positivity criterion identifies true antigen-specific CD8+ T cells.

    “CD8 + T cell reactivities were considered positive, when a clustered population was observed that was labelled with only two pMHC multimer colours.”
  • The paper relies on this without support.

    The peptide pools covering the S sequence and RBD are representative of T cell epitopes.

    “Two pools of 15-mer peptides overlapping by 11 amino acids and together covering the whole sequence of wild-type (no P2 S mutation) SARS-CoV-2 S”
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Metadata

Authors
Sahin, U., Muik, A., Vogler, I., Derhovanessian, E., Kranz, L. M., Vormehr, M., Quandt, J., Bidmon, N., Ulges, A., Baum, A., Pascal, K. E., Maurus, D., Brachtendorf, S., Lörks, V., Sikorski, J., Koch, P., Hilker, R., Becker, D., Eller, A.-K., Grützner, J., Tonigold, M., Boesler, C., Rosenbaum, C., Heesen, L., Kühnle, M.-C., Poran, A., Dong, J. Z., Luxemburger, U., Kemmer-Brück, A., Langer, D., Bexon, M., Bolte, S., Palanche, T., Schultz, A., Baumann, S., Mahiny, A. J., Boros, G., Reinholz, J., Szabó, G. T., Karikó, K., Shi, P.-Y., Fontes-Garfias, C., Perez, J. L., Cutler, M., Cooper, D., Kyratsous, C. A., Dormitzer, P. R., Jansen, K. U., & Türeci, Ö.
Affiliations
  • BioNTech (Germany) (DE)
  • Regeneron (United States) (US)
  • BioNTech (United States) (US)
  • Bexon Clinical Consulting (United States) (US)
  • Clinical Research Services (DE)
  • The University of Texas Medical Branch at Galveston (US)
  • Pfizer (United States) (US)
Venue
Nature
Published
2021-05-27
Volume
595
Issue
7868
Pages
572-577
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W3164002264
Cited by
919
References
59
Citations by year
2026: 47 · 2025: 94 · 2024: 100 · 2023: 179 · 2022: 288 · 2021: 209
FWCI
66.09
Type
journal article
Language
en
Open access
Locations
  • Nature (publishedVersion)
  • medRxiv (submittedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
Pfizer
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 › Immunology and Microbiology › Immunology › Immune responses and vaccinations
Keywords
BNT162b2, COVID-19 vaccines, SARS-CoV-2 spike protein, neutralizing antibodies, CD8+ T cells, CD4+ T helper cells, T cell epitopes, interferon-gamma, lipid nanoparticle mRNA vaccine, humoral and cellular immune response, SARS-CoV-2 variants
MeSH terms
COVID-19, SARS-CoV-2, COVID-19 Vaccines, BNT162 Vaccine, Adolescent, Adult, Antibodies, Viral, Female, Humans, Immunoglobulin G, Immunologic Memory, Interferon-gamma, Interleukin-2, Male, Middle Aged, T-Lymphocytes, CD8-Positive T-Lymphocytes, Th1 Cells, Epitopes, T-Lymphocyte, Young Adult, Antibodies, Neutralizing, Spike Glycoprotein, Coronavirus

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