T cell responses play an important role in protection against beta-coronavirus infections, including SARS-CoV-2, where they associate with decreased COVID-19 disease severity and duration. To enhance T cell immunity across epitopes infrequently altered in SARS-CoV-2 variants, we designed BNT162b4, an mRNA vaccine component that is intended 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. Importantly, we demonstrate that BNT162b4 protects hamsters from severe disease and reduces viral titers following challenge 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. BNT162b4 is currently being clinically evaluated in combination with the BA.4/BA.5 Omicron-updated bivalent BNT162b2 (NCT05541861). Display omitted •BNT162b4 encodes conserved, immunogenic segments of the SARS-CoV-2 N, M, and ORF1ab antigens•Mass spectrometry detects BNT162b4 encoded peptides bound to diverse HLA-I alleles•BNT162b4 elicits non-spike T cell responses in mice while maintaining spike immunity•BNT162b4 protects animals from severe disease and enhances viral clearance by BNT162b2 Adding non-spike targeting components to mRNA vaccination elicits promising T cell responses against SARS-CoV-2 variant strains in rodent models of COVID-19.