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 GrütznerManuel 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, Özlem Türeci

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)572-577
Number of pages6
JournalNature
Volume595
Issue number7868
DOIs
StatePublished - Jul 22 2021

ASJC Scopus subject areas

  • General

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