Concurrent human antibody andTH1 type T-cell responses elicited by a COVID-19 RNA vaccine

Sahin, U.; Muik, A.; Derhovanessian, E.; Vogler, I.; Kranz, L. M.; Vormehr, M.; Baum, A.; Pascal, K.; Quandt, J.; Maurus, D.; Brachtendorf, S.; Loerks, V. L.; Sikorski, J.; Hilker, R.; Becker, D.; Eller, A.-K.; Gruetzner, J.; Boesler, C.; Rosenbaum, C.; Kuehnle, M.-C.; Luxemburger, U.; Kemmer-Brueck, A.; Langer, D.; Bexon, M.; Bolte, S.; Kariko, K.; Palanche, T.; Fischer, B.; Schultz, A.; Shi, P.-Y.; Fontes-Garfias, C.; Perez, J. L.; Swanson, K. A.; Loschko, J.; Scully, I. L.; Cutler, M.; Kalina, W.; Kyratsous, C. A.; Cooper, D.; Dormitzer, P. R.; Jansen, K. U.; Tuereci, O.

An effective vaccine is needed to halt the spread of the SARS-CoV-2 pandemic. Recently, we reported safety, tolerability and antibody response data from an ongoing placebo-controlled, observer-blinded phase 1/2 COVID-19 vaccine trial with BNT162b1, a lipid nanoparticle (LNP) formulated nucleoside-modified messenger RNA encoding the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. Here we present antibody and T cell responses after BNT162b1 vaccination from a second, non-randomized open-label phase 1/2 trial in healthy adults, 18-55 years of age. Two doses of 1 to 50 g of BNT162b1 elicited robust CD4+ and CD8+ T cell responses and strong antibody responses, with RBD-binding IgG concentrations clearly above those in a COVID-19 convalescent human serum panel (HCS). Day 43 SARS-CoV-2 serum neutralising geometric mean titers were 0.7-fold (1 g) to 3.5-fold (50 g) those of HCS. Immune sera broadly neutralised pseudoviruses with diverse SARS-CoV-2 spike variants. Most participants had TH1 skewed T cell immune responses with RBD-specific CD8+ and CD4+ T cell expansion. Interferon (IFN){gamma} was produced by a high fraction of RBD-specific CD8+ and CD4+ T cells. The robust RBD-specific antibody, T-cell and favourable cytokine responses induced by the BNT162b1 mRNA vaccine suggest multiple beneficial mechanisms with potential to protect against COVID-19.