T-cell-directed vaccine BNT162b4

To enhance T cell immunity across epitopes infrequently altered in SARS-CoV-2 variants, this study designed BNT162b4, an mRNA vaccine component, to be combined with BNT162b2, the spike-protein-encoding vaccine. BNT162b4 encodes variant-conserved, immunogenic segments of the SARS-CoV-2 nucleocapsid, membrane, and ORF1ab proteins, targeting diverse HLA alleles. BNT162b4 elicits polyfunctional CD4 and CD8 T cell responses to diverse epitopes in animal models, alone or when co-administered with BNT162b2, while preserving spike-specific immunity. Notably, the study demonstrates that BNT162b4 protects hamsters from severe disease and reduces viral titers following challenges with viral variants. These data suggest that a combination of BNT162b2 and BNT162b4 could reduce COVID-19 disease severity and duration caused by circulating or future variants.