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BNT162b2 vaccine induces neutralizing antibodies and poly-specific T cells in humans.
Nature. 2021 07; 595(7868):572-577.Nat

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.

Authors+Show Affiliations

BioNTech, Mainz, Germany. Ugur.Sahin@biontech.de. TRON gGmbH - Translational Oncology at the University Medical Center of the Johannes Gutenberg University, Mainz, Germany. Ugur.Sahin@biontech.de.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech US, Cambridge, MA, USA.BioNTech US, Cambridge, MA, USA.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.Bexon Clinical Consulting LLC, Upper Montclair, NJ, USA.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.CRS Clinical Research Services Mannheim GmbH, Mannheim, Germany.CRS Clinical Research Services Berlin GmbH, Berlin, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.University of Texas Medical Branch, Galveston, TX, USA.University of Texas Medical Branch, Galveston, TX, USA.Pfizer, Pearl River, NY, US.Pfizer, Pearl River, NY, US.Pfizer, Pearl River, NY, US.Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.Pfizer, Pearl River, NY, US.Pfizer, Pearl River, NY, US.BioNTech, Mainz, Germany.

Pub Type(s)

Clinical Trial, Phase I
Clinical Trial, Phase II
Journal Article

Language

eng

PubMed ID

34044428

Citation

Sahin, Ugur, et al. "BNT162b2 Vaccine Induces Neutralizing Antibodies and Poly-specific T Cells in Humans." Nature, vol. 595, no. 7868, 2021, pp. 572-577.
Sahin U, Muik A, Vogler I, et al. BNT162b2 vaccine induces neutralizing antibodies and poly-specific T cells in humans. Nature. 2021;595(7868):572-577.
Sahin, U., Muik, A., Vogler, I., Derhovanessian, E., Kranz, L. M., Vormehr, M., Quandt, J., Bidmon, N., Ulges, A., Baum, A., Pascal, K. E., Maurus, D., Brachtendorf, S., Lörks, V., Sikorski, J., Koch, P., Hilker, R., Becker, D., Eller, A. K., ... Türeci, Ö. (2021). BNT162b2 vaccine induces neutralizing antibodies and poly-specific T cells in humans. Nature, 595(7868), 572-577. https://doi.org/10.1038/s41586-021-03653-6
Sahin U, et al. BNT162b2 Vaccine Induces Neutralizing Antibodies and Poly-specific T Cells in Humans. Nature. 2021;595(7868):572-577. PubMed PMID: 34044428.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - BNT162b2 vaccine induces neutralizing antibodies and poly-specific T cells in humans. AU - Sahin,Ugur, AU - Muik,Alexander, AU - Vogler,Isabel, AU - Derhovanessian,Evelyna, AU - Kranz,Lena M, AU - Vormehr,Mathias, AU - Quandt,Jasmin, AU - Bidmon,Nicole, AU - Ulges,Alexander, AU - Baum,Alina, AU - Pascal,Kristen E, AU - Maurus,Daniel, AU - Brachtendorf,Sebastian, AU - Lörks,Verena, AU - Sikorski,Julian, AU - Koch,Peter, AU - Hilker,Rolf, AU - Becker,Dirk, AU - Eller,Ann-Kathrin, AU - Grützner,Jan, AU - Tonigold,Manuel, AU - Boesler,Carsten, AU - Rosenbaum,Corinna, AU - Heesen,Ludwig, AU - Kühnle,Marie-Cristine, AU - Poran,Asaf, AU - Dong,Jesse Z, AU - Luxemburger,Ulrich, AU - Kemmer-Brück,Alexandra, AU - Langer,David, AU - Bexon,Martin, AU - Bolte,Stefanie, AU - Palanche,Tania, AU - Schultz,Armin, AU - Baumann,Sybille, AU - Mahiny,Azita J, AU - Boros,Gábor, AU - Reinholz,Jonas, AU - Szabó,Gábor T, AU - Karikó,Katalin, AU - Shi,Pei-Yong, AU - Fontes-Garfias,Camila, AU - Perez,John L, AU - Cutler,Mark, AU - Cooper,David, AU - Kyratsous,Christos A, AU - Dormitzer,Philip R, AU - Jansen,Kathrin U, AU - Türeci,Özlem, Y1 - 2021/05/27/ PY - 2020/12/09/received PY - 2021/05/19/accepted PY - 2021/5/28/pubmed PY - 2021/7/29/medline PY - 2021/5/27/entrez SP - 572 EP - 577 JF - Nature JO - Nature VL - 595 IS - 7868 N2 - 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. SN - 1476-4687 UR - https://www.unboundmedicine.com/medline/citation/34044428/BNT162b2_vaccine_induces_neutralizing_antibodies_and_poly_specific_T_cells_in_humans_ L2 - https://doi.org/10.1038/s41586-021-03653-6 DB - PRIME DP - Unbound Medicine ER -