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

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-19 1 . Here we extend a previous phase-I/II trial report 2 by presenting data on the i...

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Vydáno v:	Nature (London) Ročník 595; číslo 7868; s. 572 - 577
Hlavní autoři:	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
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 22.07.2021 Nature Publishing Group
Témata:	13 13/21 13/31 14/1 14/34 631/154/1438 631/250/255/2514 631/326/596/4130 631/61/391 692/308/153 692/700/459/1748 Adolescent Adult Antibodies Antibodies, Neutralizing - immunology Antibodies, Viral - immunology Antigens BNT162 Vaccine CD4 antigen CD8 antigen CD8-Positive T-Lymphocytes - immunology Cell differentiation Conformation Coronaviruses COVID-19 COVID-19 - immunology COVID-19 - virology COVID-19 vaccines COVID-19 Vaccines - administration & dosage COVID-19 Vaccines - adverse effects COVID-19 Vaccines - immunology Effector cells Epitopes Epitopes, T-Lymphocyte - immunology Female Glycoproteins Health aspects Humanities and Social Sciences Humans Immune response Immune response (cell-mediated) Immune response (humoral) Immune system Immunoglobulin G - immunology Immunologic Memory Interferon-gamma - immunology Interleukin 2 Interleukin-2 - immunology Laboratories Lipids Lymphocytes Lymphocytes T Major histocompatibility complex Male Memory cells Middle Aged mRNA multidisciplinary Mutation Nanoparticles Neutralizing Pain Pandemics Phenotypes SARS-CoV-2 - chemistry SARS-CoV-2 - immunology Science Science (multidisciplinary) Severe acute respiratory syndrome coronavirus 2 Spike glycoprotein Spike Glycoprotein, Coronavirus - chemistry Spike Glycoprotein, Coronavirus - immunology T cells T-Lymphocytes - immunology Th1 Cells - immunology Vaccination Viral antibodies Young Adult Germany United States > US
ISSN:	0028-0836, 1476-4687, 1476-4687
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Shrnutí:	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-19 1 . Here we extend a previous phase-I/II trial report 2 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. In a phase-I/II trial in healthy adults, the BNT162b2 vaccine induces neutralizing antibodies and poly-specific T cells against SARS-CoV-2 epitopes that are conserved in a wide range of currently circulating variants.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	0028-0836 1476-4687 1476-4687
DOI:	10.1038/s41586-021-03653-6