Strong and early immune responses against SARS-CoV-2 in mice and rhesus macaques after BNT162b3 vaccination.

We preclinically characterize BNT162b3, a nucleoside-modified mRNA-based coronavirus disease 2019 (COVID-19) vaccine encoding a trimerized, cell surface-tethered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD-foldon), formulated in lipid nanoparticles. Intramuscular immunization with BNT162b3 induced high antigen-specific antibody titers with early seroconversion kinetics in mice and rhesus macaques. One dose of BNT162b3 induced high neutralizing antibody titers against pseudoviruses harboring the spike of the SARS-CoV-2 Wuhan-Hu-1 strain and early variants of concern up to Delta, but lower titers against Omicron, the phylogenetically more distant variant. In mice, a second immunization boosted Omicron neutralizing antibody titers to levels comparable to those of other tested variants. The cellular immune response was T helper 1 cell driven. The cell surface-tethered RBD-foldon was more immunogenic than its soluble counterpart. This study demonstrated the suitability of BNT162b3 as COVID-19 vaccine and supported its evaluation in a phase I/II clinical trial (BNT162-04, NCT04537949).