Virus-Induced CD8(+) T-Cell Immunity and Its Exploitation to Contain the SARS-CoV-2 Pandemic

The current battle against Severe Acute Respiratory Syndrome (SARS)-Coronavirus-2 benefits from the worldwide distribution of different vaccine formulations. All anti-SARS-CoV-2 vaccines in use are conceived to induce anti-Spike neutralizing antibodies. However, this strategy still has unresolved issues, the most relevant of which are: (i) the resistance to neutralizing antibodies of emerging SARS-CoV-2 variants and (ii) the waning of neutralizing antibodies. On the other hand, both pre-clinical evidence and clinical evidence support the idea that the immunity sustained by antigen-specific CD8(+) T lymphocytes can complement and also surrogate the antiviral humoral immunity. As a distinctive feature, anti-SARS-CoV-2 CD8(+) T-driven immunity maintains its efficacy even in the presence of viral protein mutations. In addition, on the basis of data obtained in survivors of the SARS-CoV epidemic, this immunity is expected to last for several years. In this review, both the mechanisms and role of CD8(+) T-cell immunity in viral infections, particularly those induced by SARS-CoV and SARS-CoV-2, are analyzed. Moreover, a CD8(+) T-cell-based vaccine platform relying on in vivo engineered extracellular vesicles is described. When applied to SARS-CoV-2, this strategy was proven to induce a strong immunogenicity, holding great promise for its translation into the clinic.