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

Sahin, Muik, Vogler, Derhovanessian, Kranz, Vormehr, Quandt, Bidmon, Ulges, Baum, Pascal, Maurus, Brachtendorf, Lörks, Sikorski, Koch, Hilker, Becker, Eller, Grützner, Tonigold, Boesler, Rosenbaum, Heesen, Kühnle, Poran, Dong, Luxemburger, Kemmer-Brück, Langer, Bexon, Bolte, Palanche, Schultz, Baumann, Mahiny, Boros, Reinholz, Szabó, Karikó, Shi, Fontes-Garfias, Perez, Cutler, Cooper, Kyratsous, Dormitzer, Jansen, Türeci (2021) BNT162b2 vaccine induces neutralizing antibodies and poly-specific T cells in humans Nature 595(7868) 572-577


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.© 2021. The Author(s), under exclusive licence to Springer Nature Limited.


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