학술논문
BNT162b2 vaccine induces neutralizing antibodies and poly-specific T cells in humans
Document Type
Article
Author
Sahin, Ugur; Muik, Alexander; Vogler, Isabel; Derhovanessian, Evelyna; Kranz, Lena M.; Vormehr, Mathias; Quandt, Jasmin; Bidmon, Nicole; Ulges, Alexander; Baum, Alina; Pascal, Kristen E.; Maurus, Daniel; Brachtendorf, Sebastian; Lörks, Verena; Sikorski, Julian; Koch, Peter; Hilker, Rolf; Becker, Dirk; Eller, Ann-Kathrin; Grützner, Jan; Tonigold, Manuel; Boesler, Carsten; Rosenbaum, Corinna; Heesen, Ludwig; Kühnle, Marie-Cristine; Poran, Asaf; Dong, Jesse Z.; Luxemburger, Ulrich; Kemmer-Brück, Alexandra; Langer, David; Bexon, Martin; Bolte, Stefanie; Palanche, Tania; Schultz, Armin; Baumann, Sybille; Mahiny, Azita J.; Boros, Gábor; Reinholz, Jonas; Szabó, Gábor T.; Karikó, Katalin; Shi, Pei-Yong; Fontes-Garfias, Camila; Perez, John L.; Cutler, Mark; Cooper, David; Kyratsous, Christos A.; Dormitzer, Philip R.; Jansen, Kathrin U.; Türeci, Özlem
Source
Nature; 20210101, Issue: Preprints p1-6, 6p
Subject
Language
ISSN
00280836; 14764687
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 report2by 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.