Significance Immunity induced by the first-generation COVID-19 vaccines may not provide effective and durable protection, either due to waning immunity or due to poor antibody cross-reactivity to new variants. Typically, T cells recognize conserved nonmutable viral epitopes and development of T cell–based vaccines might provide broad immunity to SARS-CoV-2 variants. In this study, we show that adjuvanted spike protein–based experimental vaccines elicited potent respiratory or systemic CD4 and CD8 T cell memory and protected against SARS-CoV-2, in the absence of virus-neutralizing antibodies. Thus, development of T cell–based vaccines might be key to protect against antibody-escape SARS-CoV-2 variants that can potentially overcome immunity induced by current vaccines.