COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses

doi:10.1038/s41586-020-2814-7

Clinical Trial

. 2020 Oct;586(7830):594-599.

doi: 10.1038/s41586-020-2814-7. Epub 2020 Sep 30.

COVID-19 vaccine BNT162b1 elicits human antibody and T_H1 T cell responses

Ugur Sahin^{1

2}, Alexander Muik³, Evelyna Derhovanessian³, Isabel Vogler³, Lena M Kranz³, Mathias Vormehr³, Alina Baum⁴, Kristen Pascal⁴, Jasmin Quandt³, Daniel Maurus³, Sebastian Brachtendorf³, Verena Lörks³, Julian Sikorski³, Rolf Hilker³, Dirk Becker³, Ann-Kathrin Eller³, Jan Grützner³, Carsten Boesler³, Corinna Rosenbaum³, Marie-Cristine Kühnle³, Ulrich Luxemburger³, Alexandra Kemmer-Brück³, David Langer³, Martin Bexon⁵, Stefanie Bolte³, Katalin Karikó³, Tania Palanche³, Boris Fischer³, Armin Schultz⁶, Pei-Yong Shi⁷, Camila Fontes-Garfias⁷, John L Perez⁸, Kena A Swanson⁸, Jakob Loschko⁸, Ingrid L Scully⁸, Mark Cutler⁸, Warren Kalina⁸, Christos A Kyratsous⁴, David Cooper⁸, Philip R Dormitzer⁸, Kathrin U Jansen⁸, Özlem Türeci³

Affiliations

¹ BioNTech, Mainz, Germany. ugur.sahin@biontech.de.
² TRON gGmbH-Translational Oncology at the University Medical Center of the Johannes Gutenberg, Mainz, Germany. ugur.sahin@biontech.de.
³ BioNTech, Mainz, Germany.
⁴ Regeneron Pharmaceuticals, Tarrytown, NY, USA.
⁵ Bexon Clinical Consulting, Upper Montclair, NJ, USA.
⁶ CRS Clinical Research Services Mannheim GmbH, Mannheim, Germany.
⁷ University of Texas Medical Branch, Galveston, TX, USA.
⁸ Pfizer, Pearl River, NY, USA.

PMID: 32998157
DOI: 10.1038/s41586-020-2814-7

Clinical Trial

COVID-19 vaccine BNT162b1 elicits human antibody and T_H1 T cell responses

Ugur Sahin et al. Nature. 2020 Oct.

. 2020 Oct;586(7830):594-599.

doi: 10.1038/s41586-020-2814-7. Epub 2020 Sep 30.

Authors

Affiliations

¹ BioNTech, Mainz, Germany. ugur.sahin@biontech.de.
² TRON gGmbH-Translational Oncology at the University Medical Center of the Johannes Gutenberg, Mainz, Germany. ugur.sahin@biontech.de.
³ BioNTech, Mainz, Germany.
⁴ Regeneron Pharmaceuticals, Tarrytown, NY, USA.
⁵ Bexon Clinical Consulting, Upper Montclair, NJ, USA.
⁶ CRS Clinical Research Services Mannheim GmbH, Mannheim, Germany.
⁷ University of Texas Medical Branch, Galveston, TX, USA.
⁸ Pfizer, Pearl River, NY, USA.

PMID: 32998157
DOI: 10.1038/s41586-020-2814-7

Erratum in

Publisher Correction: COVID-19 vaccine BNT162b1 elicits human antibody and T_H1 T cell responses.
Sahin U, Muik A, Derhovanessian E, Vogler I, Kranz LM, Vormehr M, Baum A, Pascal K, Quandt J, Maurus D, Brachtendorf S, Lörks V, Sikorski J, Hilker R, Becker D, Eller AK, Grützner J, Boesler C, Rosenbaum C, Kühnle MC, Luxemburger U, Kemmer-Brück A, Langer D, Bexon M, Bolte S, Karikó K, Palanche T, Fischer B, Schultz A, Shi PY, Fontes-Garfias C, Perez JL, Swanson KA, Loschko J, Scully IL, Cutler M, Kalina W, Kyratsous CA, Cooper D, Dormitzer PR, Jansen KU, Türeci Ö. Sahin U, et al. Nature. 2021 Feb;590(7844):E17. doi: 10.1038/s41586-020-03102-w. Nature. 2021. PMID: 33469214 No abstract available.

Abstract

An effective vaccine is needed to halt the spread of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic. Recently, we reported safety, tolerability and antibody response data from an ongoing placebo-controlled, observer-blinded phase I/II coronavirus disease 2019 (COVID-19) vaccine trial with BNT162b1, a lipid nanoparticle-formulated nucleoside-modified mRNA that encodes the receptor binding domain (RBD) of the SARS-CoV-2 spike protein¹. Here we present antibody and T cell responses after vaccination with BNT162b1 from a second, non-randomized open-label phase I/II trial in healthy adults, 18-55 years of age. Two doses of 1-50 μg of BNT162b1 elicited robust CD4⁺ and CD8⁺ T cell responses and strong antibody responses, with RBD-binding IgG concentrations clearly above those seen in serum from a cohort of individuals who had recovered from COVID-19. Geometric mean titres of SARS-CoV-2 serum-neutralizing antibodies on day 43 were 0.7-fold (1-μg dose) to 3.5-fold (50-μg dose) those of the recovered individuals. Immune sera broadly neutralized pseudoviruses with diverse SARS-CoV-2 spike variants. Most participants had T helper type 1 (T_H1)-skewed T cell immune responses with RBD-specific CD8⁺ and CD4⁺ T cell expansion. Interferon-γ was produced by a large fraction of RBD-specific CD8⁺ and CD4⁺ T cells. The robust RBD-specific antibody, T cell and favourable cytokine responses induced by the BNT162b1 mRNA vaccine suggest that it has the potential to protect against COVID-19 through multiple beneficial mechanisms.

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Comment in

Steroid-responsive aseptic meningitis after BNT162b2 SARS-CoV-2 vaccine.
Reis Carneiro D, Matos A, Morgadinho A. Reis Carneiro D, et al. Rev Neurol (Paris). 2022 Jan-Feb;178(1-2):160-161. doi: 10.1016/j.neurol.2021.10.002. Epub 2021 Nov 4. Rev Neurol (Paris). 2022. PMID: 34799078 Free PMC article. No abstract available.

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References

1. Mulligan, M. J. et al. Phase 1/2 study of COVID-19 RNA vaccine BNT162b1 in adults. Nature https://doi.org/10.1038/s41586-020-2639-4 (2020).
1. WHO. Coronavirus Disease (COVID-19) Dashboard (accessed 17 September 2020); https://covid19.who.int/
1. Habibzadeh, P. & Stoneman, E. K. The novel coronavirus: a bird’s eye view. Int. J. Occup. Environ. Med. 11, 65–71 (2020). - DOI
1. Pardi, N. et al. Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses. J. Exp. Med. 215, 1571–1588 (2018). - DOI
1. Sahin, U., Karikó, K. & Türeci, Ö. mRNA-based therapeutics—developing a new class of drugs. Nat. Rev. Drug Discov. 13, 759–780 (2014). - DOI

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[1] Mulligan, M. J. et al. Phase 1/2 study of COVID-19 RNA vaccine BNT162b1 in adults. Nature https://doi.org/10.1038/s41586-020-2639-4 (2020).

[2] Mulligan, M. J. et al. Phase 1/2 study of COVID-19 RNA vaccine BNT162b1 in adults. Nature https://doi.org/10.1038/s41586-020-2639-4 (2020).

[3] WHO. Coronavirus Disease (COVID-19) Dashboard (accessed 17 September 2020); https://covid19.who.int/

[4] WHO. Coronavirus Disease (COVID-19) Dashboard (accessed 17 September 2020); https://covid19.who.int/

[5] Habibzadeh, P. & Stoneman, E. K. The novel coronavirus: a bird’s eye view. Int. J. Occup. Environ. Med. 11, 65–71 (2020). - DOI

[6] Habibzadeh, P. & Stoneman, E. K. The novel coronavirus: a bird’s eye view. Int. J. Occup. Environ. Med. 11, 65–71 (2020). - DOI

[7] Pardi, N. et al. Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses. J. Exp. Med. 215, 1571–1588 (2018). - DOI

[8] Pardi, N. et al. Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses. J. Exp. Med. 215, 1571–1588 (2018). - DOI

[9] Sahin, U., Karikó, K. & Türeci, Ö. mRNA-based therapeutics—developing a new class of drugs. Nat. Rev. Drug Discov. 13, 759–780 (2014). - DOI

[10] Sahin, U., Karikó, K. & Türeci, Ö. mRNA-based therapeutics—developing a new class of drugs. Nat. Rev. Drug Discov. 13, 759–780 (2014). - DOI

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COVID-19 vaccine BNT162b1 elicits human antibody and T_H1 T cell responses

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COVID-19 vaccine BNT162b1 elicits human antibody and T_H1 T cell responses

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