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

Ugur Sahin (), Alexander Muik, Isabel Vogler, Evelyna Derhovanessian, Lena M. Kranz, Mathias Vormehr, Jasmin Quandt, Nicole Bidmon, Alexander Ulges, Alina Baum, Kristen E. Pascal, Daniel Maurus, Sebastian Brachtendorf, Verena Lörks, Julian Sikorski, Peter Koch, Rolf Hilker, Dirk Becker, Ann-Kathrin Eller, Jan Grützner, Manuel Tonigold, Carsten Boesler, Corinna Rosenbaum, Ludwig Heesen, Marie-Cristine Kühnle, Asaf Poran, Jesse Z. Dong, Ulrich Luxemburger, Alexandra Kemmer-Brück, David Langer, Martin Bexon, Stefanie Bolte, Tania Palanche, Armin Schultz, Sybille Baumann, Azita J. Mahiny, Gábor Boros, Jonas Reinholz, Gábor T. Szabó, Katalin Karikó, Pei-Yong Shi, Camila Fontes-Garfias, John L. Perez, Mark Cutler, David Cooper, Christos A. Kyratsous, Philip R. Dormitzer, Kathrin U. Jansen and Özlem Türeci
Additional contact information
Ugur Sahin: BioNTech
Alexander Muik: BioNTech
Isabel Vogler: BioNTech
Evelyna Derhovanessian: BioNTech
Lena M. Kranz: BioNTech
Mathias Vormehr: BioNTech
Jasmin Quandt: BioNTech
Nicole Bidmon: BioNTech
Alexander Ulges: BioNTech
Alina Baum: Regeneron Pharmaceuticals, Inc.
Kristen E. Pascal: Regeneron Pharmaceuticals, Inc.
Daniel Maurus: BioNTech
Sebastian Brachtendorf: BioNTech
Verena Lörks: BioNTech
Julian Sikorski: BioNTech
Peter Koch: BioNTech
Rolf Hilker: BioNTech
Dirk Becker: BioNTech
Ann-Kathrin Eller: BioNTech
Jan Grützner: BioNTech
Manuel Tonigold: BioNTech
Carsten Boesler: BioNTech
Corinna Rosenbaum: BioNTech
Ludwig Heesen: BioNTech
Marie-Cristine Kühnle: BioNTech
Asaf Poran: BioNTech US
Jesse Z. Dong: BioNTech US
Ulrich Luxemburger: BioNTech
Alexandra Kemmer-Brück: BioNTech
David Langer: BioNTech
Martin Bexon: Bexon Clinical Consulting LLC
Stefanie Bolte: BioNTech
Tania Palanche: BioNTech
Armin Schultz: CRS Clinical Research Services Mannheim GmbH
Sybille Baumann: CRS Clinical Research Services Berlin GmbH
Azita J. Mahiny: BioNTech
Gábor Boros: BioNTech
Jonas Reinholz: BioNTech
Gábor T. Szabó: BioNTech
Katalin Karikó: BioNTech
Pei-Yong Shi: University of Texas Medical Branch
Camila Fontes-Garfias: University of Texas Medical Branch
John L. Perez: Pfizer
Mark Cutler: Pfizer
David Cooper: Pfizer
Christos A. Kyratsous: Regeneron Pharmaceuticals, Inc.
Philip R. Dormitzer: Pfizer
Kathrin U. Jansen: Pfizer
Özlem Türeci: BioNTech

Nature, 2021, vol. 595, issue 7868, 572-577

Abstract: 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-191. Here we extend a previous phase-I/II trial report2 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.

Date: 2021
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DOI: 10.1038/s41586-021-03653-6

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