T-Cell Immune Responses to SARS-CoV-2 Infection and Vaccination

The innate and adaptive immune systems collaborate to detect SARS-CoV-2 infection, minimize the viral spread, and kill infected cells, ultimately leading to the resolution of the infection. The adaptive immune system develops a memory of previous encounters with the virus, providing enhanced responses when rechallenged by the same pathogen. Such immunological memory is the basis of vaccine function. Here, we review the current knowledge on the immune response to SARS-CoV-2 infection and vaccination, focusing on the pivotal role of T cells in establishing protective immunity against the virus. After providing an overview of the immune response to SARS-CoV-2 infection, we describe the main features of SARS-CoV-2-specific CD4⁺ and CD8⁺ T cells, including cross-reactive T cells, generated in patients with different degrees of COVID-19 severity, and of Spike-specific CD4⁺ and CD8⁺ T cells induced by vaccines. Finally, we discuss T-cell responses to SARS-CoV-2 variants and hybrid immunity and conclude by highlighting possible strategies to improve the efficacy of COVID-19 vaccination.