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

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

BNT162b2, a lipid nanoparticle (LNP) formulated nucleoside-modified messenger RNA (mRNA) that encodes the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike glycoprotein (S) stabilized in the prefusion conformation, has demonstrated 95% efficacy in preventing coronavirus disease-19 (COVID-19)1. Here we extend our previous phase 1/2 trial report2 and present BNT162b2 prime/boost induced immune response data from a second phase 1/2 trial in healthy adults (18-55 years of age). BNT162b2 elicited strong antibody responses, with SARS-CoV-2 serum 50% neutralizing geometric mean titers up to 3.3-fold above those observed in COVID-19 human convalescent samples (HCS) one week post-boost. BNT162b2-elicited sera neutralized 22 pseudoviruses bearing SARS-CoV-2 S variants. Most participants had a strong IFNγ- or IL-2-positive CD8+ and CD4+ T helper type 1 (TH1) T cell response, detectable throughout the full observation period of nine weeks following the boost. pMHC multimer technology identified several BNT162b2-induced epitopes that were presented by frequent MHC alleles and conserved in mutant strains. One week post-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 conserved in a broad range of variants at well tolerated doses.